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Sample records for advance drug treatments

  1. Protein Innovations Advance Drug Treatments, Skin Care

    NASA Technical Reports Server (NTRS)

    2012-01-01

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

  2. Recent advancements in drug treatment of obesity.

    PubMed

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

    2012-10-01

    The prevalence of obesity is rising worldwide, with the U.K. having the highest prevalence in Europe. Obesity is associated with significant morbidity and has substantial healthcare implications, with current projections estimating that by 2030 obesity will cost the NHS approximately pounds 2 billion each year. Lifestyle modification remains the cornerstone of anti-obesity treatment, but drugs can be introduced as adjuncts to assist and maintain weight loss. Some 1.45 million obesity-related prescriptions were dispensed in 2009, highlighting the high demand for obesity pharmacotherapy. At present, the lipase inhibitor orlistat (Xenical) is the only UK-approved long-term medical therapy for obesity. Double-blind clinical trials have shown that orlistat significantly increases weight loss compared to placebo, but the array of adverse side effects associated with orlistat limits its tolerability. The need for more effective and better-tolerated anti-obesity medications is clear and six therapies have reached phase-III trials. PMID:23101148

  3. Recent advances in tuberculosis: New drugs and treatment regimens.

    PubMed

    Sloan, Derek J; Davies, Geraint R; Khoo, Saye H

    2013-06-01

    The current treatment regimen against drug susceptible tuberculosis (DS-TB) was defined by the 1980s. Since then the emergence of the global HIV pandemic and the escalation of drug resistant (DR-) forms of TB have presented new challenges for therapeutic research. Priority goals include shortening DS-TB treatment, improving DR-TB treatment and making combined TB-HIV therapy easier. To help achieve these goals, a range of new drugs and treatment strategies are currently being evaluated. Phase IIb and III clinical trials are ongoing to assess combinations involving the high-dose rifamycins, the 8-methoxyquinolones, a diarylquinoline (bedaquiline) and the nitroimidazoles. Other compounds (e.g. novel oxazolidinones and ethylenediamines) are at earlier stages of clinical development. Overall, there are grounds for optimism that recent advances will contribute towards achievement of new treatment regimens in the foreseeable future. However, long-term investment, political commitment and scientific endeavour are crucial to ensure that progress is sustained and the benefits of recent advances reach those in the greatest need.

  4. Advancing drug delivery systems for the treatment of multiple sclerosis.

    PubMed

    Tabansky, Inna; Messina, Mark D; Bangeranye, Catherine; Goldstein, Jeffrey; Blitz-Shabbir, Karen M; Machado, Suly; Jeganathan, Venkatesh; Wright, Paul; Najjar, Souhel; Cao, Yonghao; Sands, Warren; Keskin, Derin B; Stern, Joel N H

    2015-12-01

    Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. It is characterized by demyelination of neurons and loss of neuronal axons and oligodendrocytes. In MS, auto-reactive T cells and B cells cross the blood-brain barrier (BBB), causing perivenous demyelinating lesions that form multiple discrete inflammatory demyelinated plaques located primarily in the white matter. In chronic MS, cortical demyelination and progressive axonal transections develop. Treatment for MS can be stratified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs aim to decrease circulating immune cells or to prevent these cells from crossing the BBB and reduce the inflammatory response. There are currently 10 DMTs approved for the relapsing forms of MS; these vary with regard to their efficacy, route and frequency of administration, adverse effects, and toxicity profile. Better drug delivery systems are being developed in order to decrease adverse effects, increase drug efficacy, and increase patient compliance through the direct targeting of pathologic cells. Here, we address the uses and benefits of advanced drug delivery systems, including nanoparticles, microparticles, fusion antibodies, and liposomal formulations. By altering the properties of therapeutic particles and enhancing targeting, breakthrough drug delivery technologies potentially applicable to multiple disease treatments may rapidly emerge.

  5. Current advances in the treatment of adolescent drug use

    PubMed Central

    Winters, Ken C; Tanner-Smith, Emily E; Bresani, Elena; Meyers, Kathleen

    2014-01-01

    Research on the development and efficacy of drug abuse treatment for adolescents has made great strides recently. Several distinct models have been studied, and these approaches range from brief interventions to intensive treatments. This paper has three primary aims: to provide an overview of conceptual issues relevant to treating adolescents suspected of drug-related problems, including an overview of factors believed to contribute to a substance use disorder, to review the empirical treatment outcome literature, and to identify areas of need and promising directions for future research. PMID:25429247

  6. Intelligent Nanoparticles for Advanced Drug Delivery in Cancer Treatment

    PubMed Central

    Spencer, David S.; Puranik, Amey S.; Peppas, Nicholas A.

    2015-01-01

    Treatment of cancer using nanoparticle-based approaches relies on the rational design of carriers with respect to size, charge, and surface properties. Polymer-based nanomaterials, inorganic materials such as gold, iron oxide, and silica as well as carbon based materials such as carbon nanotubes and graphene are being explored extensively for cancer therapy. The challenges associated with the delivery of these nanoparticles depend greatly on the type of cancer and stage of development. This review highlights design considerations to develop nanoparticle-based approaches for overcoming physiological hurdles in cancer treatment, as well as emerging research in engineering advanced delivery systems for the treatment of primary, metastatic, and multidrug resistant cancers. A growing understanding of cancer biology will continue to foster development of intelligent nanoparticle-based therapeutics that take into account diverse physiological contexts of changing disease states to improve treatment outcomes. PMID:25621200

  7. Tuberculosis--advances in development of new drugs, treatment regimens, host-directed therapies, and biomarkers.

    PubMed

    Wallis, Robert S; Maeurer, Markus; Mwaba, Peter; Chakaya, Jeremiah; Rustomjee, Roxana; Migliori, Giovanni Battista; Marais, Ben; Schito, Marco; Churchyard, Gavin; Swaminathan, Soumya; Hoelscher, Michael; Zumla, Alimuddin

    2016-04-01

    Tuberculosis is the leading infectious cause of death worldwide, with 9·6 million cases and 1·5 million deaths reported in 2014. WHO estimates 480,000 cases of these were multidrug resistant (MDR). Less than half of patients who entered into treatment for MDR tuberculosis successfully completed that treatment, mainly due to high mortality and loss to follow-up. These in turn illustrate weaknesses in current treatment regimens and national tuberculosis programmes, coupled with operational treatment challenges. In this Review we provide an update on recent developments in the tuberculosis drug-development pipeline (including new and repurposed antimicrobials and host-directed drugs) as they are applied to new regimens to shorten and improve outcomes of tuberculosis treatment. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR tuberculosis, and two new antimicrobial drug candidates are in early-stage trials. Several trials to reduce the duration of therapy in MDR and drug-susceptible tuberculosis are ongoing. A wide range of candidate host-directed therapies are being developed to accelerate eradication of infection, prevent new drug resistance, and prevent permanent lung injury. As these drugs have been approved for other clinical indications, they are now ready for repurposing for tuberculosis in phase 2 clinical trials. We assess risks associated with evaluation of new treatment regimens, and highlight opportunities to advance tuberculosis research generally through regulatory innovation in MDR tuberculosis. Progress in tuberculosis-specific biomarkers (including culture conversion, PET and CT imaging, and gene expression profiles) can support this innovation. Several global initiatives now provide unique opportunities to tackle the tuberculosis epidemic through collaborative partnerships between high-income countries and middle-income and low-income countries for clinical trials training and research, allowing funders to

  8. Tuberculosis--advances in development of new drugs, treatment regimens, host-directed therapies, and biomarkers.

    PubMed

    Wallis, Robert S; Maeurer, Markus; Mwaba, Peter; Chakaya, Jeremiah; Rustomjee, Roxana; Migliori, Giovanni Battista; Marais, Ben; Schito, Marco; Churchyard, Gavin; Swaminathan, Soumya; Hoelscher, Michael; Zumla, Alimuddin

    2016-04-01

    Tuberculosis is the leading infectious cause of death worldwide, with 9·6 million cases and 1·5 million deaths reported in 2014. WHO estimates 480,000 cases of these were multidrug resistant (MDR). Less than half of patients who entered into treatment for MDR tuberculosis successfully completed that treatment, mainly due to high mortality and loss to follow-up. These in turn illustrate weaknesses in current treatment regimens and national tuberculosis programmes, coupled with operational treatment challenges. In this Review we provide an update on recent developments in the tuberculosis drug-development pipeline (including new and repurposed antimicrobials and host-directed drugs) as they are applied to new regimens to shorten and improve outcomes of tuberculosis treatment. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR tuberculosis, and two new antimicrobial drug candidates are in early-stage trials. Several trials to reduce the duration of therapy in MDR and drug-susceptible tuberculosis are ongoing. A wide range of candidate host-directed therapies are being developed to accelerate eradication of infection, prevent new drug resistance, and prevent permanent lung injury. As these drugs have been approved for other clinical indications, they are now ready for repurposing for tuberculosis in phase 2 clinical trials. We assess risks associated with evaluation of new treatment regimens, and highlight opportunities to advance tuberculosis research generally through regulatory innovation in MDR tuberculosis. Progress in tuberculosis-specific biomarkers (including culture conversion, PET and CT imaging, and gene expression profiles) can support this innovation. Several global initiatives now provide unique opportunities to tackle the tuberculosis epidemic through collaborative partnerships between high-income countries and middle-income and low-income countries for clinical trials training and research, allowing funders to

  9. Recent Advances in Delivery of Drug-Nucleic Acid Combinations for Cancer Treatment

    PubMed Central

    Li, Jing; Wang, Yan; Zhu, Yu; Oupický, David

    2013-01-01

    Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation. However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer. This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations. PMID:23624358

  10. Nanovectors for anti-cancer drug delivery in the treatment of advanced pancreatic adenocarcinoma.

    PubMed

    Hsueh, Chung-Tzu; Selim, Julie H; Tsai, James Y; Hsueh, Chung-Tsen

    2016-08-21

    Liposome, albumin and polymer polyethylene glycol are nanovector formulations successfully developed for anti-cancer drug delivery. There are significant differences in pharmacokinetics, efficacy and toxicity between pre- and post-nanovector modification. The alteration in clinical pharmacology is instrumental for the future development of nanovector-based anticancer therapeutics. We have reviewed the results of clinical studies and translational research in nanovector-based anti-cancer therapeutics in advanced pancreatic adenocarcinoma, including nanoparticle albumin-bound paclitaxel and nanoliposomal irinotecan. Furthermore, we have appraised the ongoing studies incorporating novel agents with nanomedicines in the treatment of pancreatic adenocarcinoma. PMID:27610018

  11. Nanovectors for anti-cancer drug delivery in the treatment of advanced pancreatic adenocarcinoma

    PubMed Central

    Hsueh, Chung-Tzu; Selim, Julie H; Tsai, James Y; Hsueh, Chung-Tsen

    2016-01-01

    Liposome, albumin and polymer polyethylene glycol are nanovector formulations successfully developed for anti-cancer drug delivery. There are significant differences in pharmacokinetics, efficacy and toxicity between pre- and post-nanovector modification. The alteration in clinical pharmacology is instrumental for the future development of nanovector-based anticancer therapeutics. We have reviewed the results of clinical studies and translational research in nanovector-based anti-cancer therapeutics in advanced pancreatic adenocarcinoma, including nanoparticle albumin-bound paclitaxel and nanoliposomal irinotecan. Furthermore, we have appraised the ongoing studies incorporating novel agents with nanomedicines in the treatment of pancreatic adenocarcinoma. PMID:27610018

  12. Nanovectors for anti-cancer drug delivery in the treatment of advanced pancreatic adenocarcinoma

    PubMed Central

    Hsueh, Chung-Tzu; Selim, Julie H; Tsai, James Y; Hsueh, Chung-Tsen

    2016-01-01

    Liposome, albumin and polymer polyethylene glycol are nanovector formulations successfully developed for anti-cancer drug delivery. There are significant differences in pharmacokinetics, efficacy and toxicity between pre- and post-nanovector modification. The alteration in clinical pharmacology is instrumental for the future development of nanovector-based anticancer therapeutics. We have reviewed the results of clinical studies and translational research in nanovector-based anti-cancer therapeutics in advanced pancreatic adenocarcinoma, including nanoparticle albumin-bound paclitaxel and nanoliposomal irinotecan. Furthermore, we have appraised the ongoing studies incorporating novel agents with nanomedicines in the treatment of pancreatic adenocarcinoma.

  13. Recent advances in novel heterocyclic scaffolds for the treatment of drug-resistant malaria.

    PubMed

    Kumar, Sahil; Singh, Rajesh K; Patial, Babita; Goyal, Sachin; Bhardwaj, T R

    2016-01-01

    Malaria is a major public health problem all over the world, particularly in tropical and subtropical countries due to the development of resistance and most deadly infection is caused by Plasmodium falciparum. There is a direct need for the discovery of new drugs with unique structures and mechanism of action to treat sensitive and drug-resistant strains of various plasmodia for radical cure of this disease. Traditional compounds such as quinine and related derivatives represent a major source for the development of new drugs. This review presents recent modifications of 4-aminoquinoline and 8-aminoquinolone rings as leads to novel active molecules which are under clinical trials. The review also encompasses the other heterocyclic compounds emerged as potential antimalarial agents with promising results such as acridinediones and acridinone analogues, pyridines and quinolones as antimalarials. Miscellaneous heterocyclics such as tetroxane derivatives, indole derivatives, imidazolopiperazine derivatives, biscationic choline-based compounds and polymer-linked combined antimalarial drugs are also discussed. At last brief introduction to heterocyclics in natural products is also reviewed. Most of them have been under clinical trials and found to be promising in the treatment of drug-resistant strains of Plasmodium and others can be explored for the same purpose.

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

    ERIC Educational Resources Information Center

    Miller, Roxanne Greitz

    2009-01-01

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

  15. Advances in ophthalmic drug delivery.

    PubMed

    Morrison, Peter W J; Khutoryanskiy, Vitaliy V

    2014-12-01

    Various strategies for ocular drug delivery are considered; from basic formulation techniques for improving availability of drugs; viscosity enhancers and mucoadhesives aid drug retention and penetration enhancers promote drug transport into the eye. The use of drug-loaded contact lenses and ocular inserts allows drugs to be better placed where they are needed for more direct delivery. Developments in ocular implants gives a means to overcome the physical barriers that traditionally prevented effective treatment. Implant technologies are under development allowing long-term drug delivery from a single procedure, these devices allow posterior chamber diseases to be effectively treated. Future developments could bring artificial corneas to eliminate the need for donor tissue and one-off implantable drug depots lasting the patient's lifetime.

  16. An implantable and controlled drug-release silk fibroin nanofibrous matrix to advance the treatment of solid tumour cancers.

    PubMed

    Xie, Maobin; Fan, Dejun; Chen, Yufeng; Zhao, Zheng; He, Xiaowen; Li, Gang; Chen, Aizheng; Wu, Xiaojian; Li, Jiashen; Li, Zhi; Hunt, John A; Li, Yi; Lan, Ping

    2016-10-01

    The development of more effective cancer therapeutic strategies are still critically required. The maximization of the therapeutic effect in combination with avoiding the severe side effects on normal tissues when using chemotherapy drugs is still an urgent problem that requires improvements urgently. Here we provide implantable and controllable drug-release that utilises silk fibroin (SF) as a nanofibrous drug delivery system (DDS) for cancer treatment. A nanofibrous structure with controllable fibre diameter (<100 nm) was produced. The drug release rate of the SF DDS was controlled by applying a post-treatment process. In vitro anti-cancer (HCT116) results indicated that curcumin (CM)-SF nanofibrous matrix had a superior anti-cancer potential when the concentration was >5 μg/mL. The mechanism could be explained by the cell cycle being held in the S phase. The toxic effect on normal cells (NCM460) was minimized by using a treatment concentration range (5-20 μg/mL). Implantation of this DDS into the tumour site inhibited the growth of solid tumour; this offers an alternative approach for novel cancer therapy. PMID:27376557

  17. Advancing New Antibacterial Drug Development for Treatment of Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia.

    PubMed

    Toerner, Joseph G; Rubin, Daniel

    2016-08-15

    The Clinical Trials Transformation Initiative (CTTI), a public-private partnership comprised of representatives from academia, the pharmaceutical industry, and the federal government including the US Food and Drug Administration, formed a group working toward a common goal of intensified research to facilitate the development of new antibacterial drug therapies for treatment of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). The summary of the CTTI HABP/VABP project in this supplement of Clinical Infectious Diseases is a first step in this direction. PMID:27481951

  18. [Pollinosis: drug treatments].

    PubMed

    Harf, R

    2013-06-01

    The medical treatment of allergic rhino-conjunctivitis involves different classes of drugs administered locally or by general route. They belong to three main classes, antihistamines, steroids and mast cell stabilizers. Since it is a relatively benign and also highly common disease, treatment options are limited by possible, even mild, side effects and by cost efficacy restriction. In the more severe forms of the condition, treatment efficacy remains unsatisfactory.

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

    PubMed Central

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

    2011-01-01

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

  20. Advances in Alcoholism Treatment

    PubMed Central

    Huebner, Robert B.; Kantor, Lori Wolfgang

    2011-01-01

    Researchers are working on numerous and varied approaches to improving the accessibility, quality, effectiveness, and cost-effectiveness of treatment for alcohol use disorders (AUDs). This overview article summarizes the approaches reviewed in this issue, including potential future developments for alcoholism treatment, such as medications development, behavioral therapy, advances in technology that are being used to improve treatment, integrated care of patients with AUDs and co-occurring disorders, the role of 12-step programs in the broader realm of treatment, treating patients with recurring and chronic alcohol dependence, strategies to close the gap between treatment need and treatment utilization, and how changes in the health care system may affect the delivery of treatment. This research will not only reveal new medications and behavioral therapies but also will contribute to new ways of approaching current treatment problems. PMID:23580014

  1. Recent advances in antibacterial drugs

    PubMed Central

    Rai, Jaswant; Randhawa, Gurpreet Kaur; Kaur, Mandeep

    2013-01-01

    The incidence of antimicrobial resistance is on continued rise with a threat to return to the “pre-antibiotic” era. This has led to emergence of such bacterial infections which are essentially untreatable by the current armamentarium of available treatment options. Various efforts have been made to develop the newer antimicrobials with novel modes of action which can act against these multi-drug resistant strains. This review aims to focus on these newly available and investigational antibacterials approved after year 2000, their mechanism of actions/resistance, and spectrum of activity and their phases of clinical trials. Newer unexploited targets and strategies for the next generation of antimicrobial drugs for combating the drug resistance and emerging pathogens in the 21st century have also been reviewed in the present article. PMID:23776832

  2. Advancing drug discovery for schizophrenia

    PubMed Central

    Marder, Stephen R.; Roth, Bryan; Sullivan, Patrick F.; Scolnick, Edward M.; Nestler, Eric J.; Geyer, Mark A.; Welnberger, Daniel R.; Karayiorgou, Maria; Guidotti, Alessandro; Gingrich, Jay; Akbarian, Schahram; Buchanan, Robert W.; Lieberman, Jeffrey A.; Conn, P. Jeffrey; Haggarty, Stephen J.; Law, Amanda J.; Campbell, Brian; Krystal, John H.; Moghaddam, Bita; Saw, Akira; Caron, Marc G.; George, Susan R.; Allen, John A.; Solis, Michelle

    2013-01-01

    Sponsored by the New York Academy of Sciences and with support from the National Institute of Mental Health, the Life Technologies Foundation, and the Josiah Macy Jr. Foundation, “Advancing Drug Discovery for Schizophrenia” was held March 9–11 at the New York Academy of Sciences in New York City. The meeting, comprising individual talks and panel discussions, highlighted basic, clinical, and translational research approaches, all of which contribute to the overarching goal of enhancing the pharmaceutical armamentarium for treating schizophrenia. This report surveys work by the vanguard of schizophrenia research in such topics as genetic and epigenetic approaches; small molecule therapeutics; and the relationships between target genes, neuronal function, and symptoms of schizophrenia. PMID:22032400

  3. Advances in Nanocarriers for Anticancer Drugs Delivery.

    PubMed

    Ali, Imran; Lone, Mohammad Nadeem; Suhail, Mohammad; Mukhtar, Sofi Danish; Asnin, Leonid

    2016-01-01

    Cancer is the most dangerous disease to haunt the mankind in the world today. Generally, the overall cancer mortality rates are similar in both the sexes. The reasons for most of these deaths are inefficacy and failure of the current methods of treatments or the unavailability of treatment options. The researchers of the world are actively integrating nanotechnology of treating of various cancers. The development of smart nanocarriers is one of the most important innovations in this direction. The nanocarriers of the different materials are being developed to improve the efficacy of current treatments. The present article describes the role of nanotechnology in cancer treatment emphasizing cancer nanotherapy, nanocarriers for drug delivery, types and the mechanisms of the nanocarriers. Besides, the efforts are made to discuss the recent advances in the nanocarriers, current challenges and the future prospective. PMID:27048343

  4. Important drugs for cough in advanced cancer.

    PubMed

    Homsi, J; Walsh, D; Nelson, K A

    2001-11-01

    Cough is a defense mechanism that prevents the entry of noxious materials into the respiratory system and clears foreign materials and excess secretions from the lungs and respiratory tract. In advanced cancer, it is a common symptom that interferes with the patient's daily activity and quality of life. Empiric treatment with antitussive agents is often needed. Two classes of antitussive drugs are available: (1) centrally acting: (a) opioids and (b) non-opioids; (2) peripherally acting: (a) directly and (b) indirectly. Antitussive availability varies widely around the world. Many antitussives, such as benzonatate, codeine, hydrocodone, and dextromethorphan, were extensively studied in the acute and chronic cough settings and showed relatively high efficacy and safety profiles. Benzonatate, clobutinol, dihydrocodeine, hydrocodone, and levodropropizine were the only antitussives specifically studied in cancer and advanced cancer cough. They all have shown to be effective and safe in recommended daily dose for cough. In advanced cancer the patient's current medications, previous antitussive use, the availability of routes of administration, any history of drug abuse, the presence of other symptoms and other factors, all have a role in the selection of antitussives for prescription. A good knowledge of the pharmacokinetics, dosage, efficacy, and side effects of the available antitussives provides for better management.

  5. Important drugs for cough in advanced cancer.

    PubMed

    Homsi, J; Walsh, D; Nelson, K A

    2001-11-01

    Cough is a defense mechanism that prevents the entry of noxious materials into the respiratory system and clears foreign materials and excess secretions from the lungs and respiratory tract. In advanced cancer, it is a common symptom that interferes with the patient's daily activity and quality of life. Empiric treatment with antitussive agents is often needed. Two classes of antitussive drugs are available: (1) centrally acting: (a) opioids and (b) non-opioids; (2) peripherally acting: (a) directly and (b) indirectly. Antitussive availability varies widely around the world. Many antitussives, such as benzonatate, codeine, hydrocodone, and dextromethorphan, were extensively studied in the acute and chronic cough settings and showed relatively high efficacy and safety profiles. Benzonatate, clobutinol, dihydrocodeine, hydrocodone, and levodropropizine were the only antitussives specifically studied in cancer and advanced cancer cough. They all have shown to be effective and safe in recommended daily dose for cough. In advanced cancer the patient's current medications, previous antitussive use, the availability of routes of administration, any history of drug abuse, the presence of other symptoms and other factors, all have a role in the selection of antitussives for prescription. A good knowledge of the pharmacokinetics, dosage, efficacy, and side effects of the available antitussives provides for better management. PMID:11762966

  6. Prevention and drug treatment.

    PubMed

    Testa, Mark F; Smith, Brenda

    2009-01-01

    Evidence linking alcohol and other drug abuse with child maltreatment, particularly neglect, is strong. But does substance abuse cause maltreatment? According to Mark Testa and Brenda Smith, such co-occurring risk factors as parental depression, social isolation, homelessness, or domestic violence may be more directly responsible than substance abuse itself for maltreatment. Interventions to prevent substance abuse-related maltreatment, say the authors, must attend to the underlying direct causes of both. Research on whether prevention programs reduce drug abuse or help parents control substance use and improve their parenting has had mixed results, at best. The evidence raises questions generally about the effectiveness of substance abuse services in preventing child maltreatment. Such services, for example, raise only marginally the rates at which parents are reunified with children who have been placed in foster care. The primary reason for the mixed findings, say Testa and Smith, is that almost all the parents face not only substance abuse problems but the co-occurring issues as well. To prevent recurring maltreatment and promote reunification, programs must ensure client progress in all problem areas. At some point in the intervention process, say Testa and Smith, attention must turn to the child's permanency needs and well-being. The best evidence to date suggests that substance-abusing parents pose no greater risk to their children than do parents of other children taken into child protective custody. It may be sensible, say the authors, to set a six-month timetable for parents to engage in treatment and allow twelve to eighteen months for them to show sufficient progress in all identified problem areas. After that, permanency plans should be expedited to place the child with a relative caregiver or in an adoptive home. Investing in parental recovery from substance abuse and dependence, the authors conclude, should not substitute for a comprehensive approach

  7. Macrosystemic Approaches to Drug Treatment.

    ERIC Educational Resources Information Center

    Bokos, Peter J.; And Others

    1984-01-01

    Conducted a three-year observational study of clients (N=100) receiving methadone treatment in three drug abuse programs. Concluded that the chemotherapeutic treatment system itself fosters addictive behavior and recommended changes within the clinics and the macrosystem. (LLL)

  8. Prevention and Drug Treatment

    ERIC Educational Resources Information Center

    Testa, Mark F.; Smith, Brenda

    2009-01-01

    Evidence linking alcohol and other drug abuse with child maltreatment, particularly neglect, is strong. But does substance abuse cause maltreatment? According to Mark Testa and Brenda Smith, such co-occurring risk factors as parental depression, social isolation, homelessness, or domestic violence may be more directly responsible than substance…

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

    PubMed

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

    2015-12-01

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

  10. Recent advances of cocktail chemotherapy by combination drug delivery systems.

    PubMed

    Hu, Quanyin; Sun, Wujin; Wang, Chao; Gu, Zhen

    2016-03-01

    Combination chemotherapy is widely exploited for enhanced cancer treatment in the clinic. However, the traditional cocktail administration of combination regimens often suffers from varying pharmacokinetics among different drugs. The emergence of nanotechnology offers an unparalleled opportunity for developing advanced combination drug delivery strategies with the ability to encapsulate various drugs simultaneously and unify the pharmacokinetics of each drug. This review surveys the most recent advances in combination delivery of multiple small molecule chemotherapeutics using nanocarriers. The mechanisms underlying combination chemotherapy, including the synergistic, additive and potentiation effects, are also discussed with typical examples. We further highlight the sequential and site-specific co-delivery strategies, which provide new guidelines for development of programmable combination drug delivery systems. Clinical outlook and challenges are also discussed in the end.

  11. Role of microemuslsions in advanced drug delivery.

    PubMed

    Sharma, Aman Kumar; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-06-01

    Microemulsions have gained significant attention from formulation scientists since the time they have been discovered, because of their excellent properties related to their stability, solubility, simplicity, and formulation aspects. The application of microemulsions is not limited to drug delivery via the oral, topical or ocular routes, but may also be seen in cosmetics, immunology, sensor devices, coating, textiles, analytical chemistry, and spermicide. Finally, the objective of this review is to discuss briefly the applications of microemulsions in advanced drug delivery. PMID:25711493

  12. Nintedanib in combination with docetaxel for second-line treatment of advanced non-small-cell lung cancer; GENESIS-SEFH drug evaluation report.

    PubMed

    Espinosa Bosch, María; Asensi Diez, Rocío; García Agudo, Sara; Clopes Estela, Ana

    2016-01-01

    Nintedanib is a triple angiokinase inhibitor that has been approved by the European Agency Medicines (EMA) in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non small cell lung cancer (NSCLC) of adenocarcinoma tumour histology, after first-line chemotherapy. In LUME-Lung 1 clinical trial, the combination of nintedanib plus docetaxel vs. placebo plus docetaxel improved progression free survival (PFS) in NSCLC patients, and improved overall survival in the population of adenocarcinoma patients, particularly in those with progression within 9 months after first line treatment initiation, median 10.9 months ( [95% CI 8.5-12.6] vs. 7.9 months [6.7-9.1]; HR 0.75 [95% CI 0.60-0.92], p=0.0073). The toxicity profile of the combination included a higher incidence of neutropenia, gastro-intestinal (GI) disorders, and liver enzyme elevations; however, this did not cause a detrimental effect on patient quality of life. According to data from the clinical trial mentioned, the addition of nintedanib to docetaxel would lead to an estimated incremental cost-effectiveness ratio (ICER) per year of life with PFS in the overall population of 134,274.47 € (notified price). In the adenocarcinoma population per each life of year gained (LYG), the ICER of adding nintedanib to docetaxel would be 40,886.14 €; while by implementing a sensitivity analysis with a 25% discount in the drug price, the cost per LYG would be 32,364.05 €, and would place it close to the threshold of cost-effectiveness usually considered acceptable in our setting. In view of efficacy and safety results the proposed positioning is to recommend its inclusion in the Hospital Formulary only for adult patients with metastatic or locally recurrent NSCLC with adenocarcinoma histology after first line chemotherapy, with progression < 9 months from the initiation of first line treatment, taking into account the inclusion and exclusion criteria in the

  13. Nintedanib in combination with docetaxel for second-line treatment of advanced non-small-cell lung cancer; GENESIS-SEFH drug evaluation report.

    PubMed

    Espinosa Bosch, María; Asensi Diez, Rocío; García Agudo, Sara; Clopes Estela, Ana

    2016-06-01

    Nintedanib is a triple angiokinase inhibitor that has been approved by the European Agency Medicines (EMA) in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non small cell lung cancer (NSCLC) of adenocarcinoma tumour histology, after first-line chemotherapy. In LUME-Lung 1 clinical trial, the combination of nintedanib plus docetaxel vs. placebo plus docetaxel improved progression free survival (PFS) in NSCLC patients, and improved overall survival in the population of adenocarcinoma patients, particularly in those with progression within 9 months after first line treatment initiation, median 10.9 months ( [95% CI 8.5-12.6] vs. 7.9 months [6.7-9.1]; HR 0.75 [95% CI 0.60-0.92], p=0.0073). The toxicity profile of the combination included a higher incidence of neutropenia, gastro-intestinal (GI) disorders, and liver enzyme elevations; however, this did not cause a detrimental effect on patient quality of life. According to data from the clinical trial mentioned, the addition of nintedanib to docetaxel would lead to an estimated incremental cost-effectiveness ratio (ICER) per year of life with PFS in the overall population of 134,274.47 € (notified price). In the adenocarcinoma population per each life of year gained (LYG), the ICER of adding nintedanib to docetaxel would be 40,886.14 €; while by implementing a sensitivity analysis with a 25% discount in the drug price, the cost per LYG would be 32,364.05 €, and would place it close to the threshold of cost-effectiveness usually considered acceptable in our setting. In view of efficacy and safety results the proposed positioning is to recommend its inclusion in the Hospital Formulary only for adult patients with metastatic or locally recurrent NSCLC with adenocarcinoma histology after first line chemotherapy, with progression < 9 months from the initiation of first line treatment, taking into account the inclusion and exclusion criteria in the

  14. Recent advances in ophthalmic drug delivery

    PubMed Central

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

    2011-01-01

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

  15. Advanced Treatment for Basal Cell Carcinomas

    PubMed Central

    Atwood, Scott X.; Whitson, Ramon J.; Oro, Anthony E.

    2014-01-01

    Basal cell carcinomas (BCCs) are very common epithelial cancers that depend on the Hedgehog pathway for tumor growth. Traditional therapies such as surgical excision are effective for most patients with sporadic BCC; however, better treatment options are needed for cosmetically sensitive or advanced and metastatic BCC. The first approved Hedgehog antagonist targeting the membrane receptor Smoothened, vismodegib, shows remarkable effectiveness on both syndromic and nonsyndromic BCCs. However, drug-resistant tumors frequently develop, illustrating the need for the development of next-generation Hedgehog antagonists targeting pathway components downstream from Smoothened. In this article, we will summarize available BCC treatment options and discuss the development of next-generation antagonists. PMID:24985127

  16. Advances in psoriasis physiopathology and treatments: Up to date of mechanistic insights and perspectives of novel therapies based on innovative skin drug delivery systems (ISDDS).

    PubMed

    Sala, M; Elaissari, A; Fessi, H

    2016-10-10

    Psoriasis is a chronic inflammatory disease affecting mainly the skin but which can be complicated by psoriatic arthritis (PsA).This autoimmune skin disorder concerns 2-5% of the world population. To date, the physiopathology of psoriasis is not still completely elucidated but many researches are ongoing which have led for example to the discovery of the Th17/Th22 pathway. The conventional therapeutic approaches (local or systemic route) appeal to various classes of drugs with complex mechanisms of action and non-negligible side effects. Although there is no therapy capable to cure psoriasis, the current goal is to relieve symptoms as longer as possible with a good benefit/risk ratio. That is one of the principal limits of conventional antipsoriatic drugs. New formulations based on nanoencapsulation are a promising opportunity to answer to this limit by offering an optimization of the conventional antipsoriatic drug use (higher activity, lower side effects and frequency of application, etc.). Herein, we tried to put in perspective the mechanistic insights (histological and immunological views) proposed into scientific literature these last years in order to have a better comprehension of psoriasis physiopathology resulting in skin lesions and PsA. The therapeutic armamentarium and the different strategies in the management of psoriasis are discussed in greater details. To finish, the field of encapsulation in nanoparticles is broached in order to put forward recent advances in innovative skin drug delivery systems (ISDDSs) of antipsoriatic active agents for a better efficacy, safety and compliance.

  17. Polymer Drug Conjugates: Recent Advancements in Various Diseases.

    PubMed

    Singh, Jasbir; Desai, Sapna; Yadav, Snehlata; Narasimhan, Balasubramanian; Kaur, Harmeet

    2016-01-01

    During the past decade, the arena of polymer therapeutics has acquired considerable interest and accompanied by advanced designs and chemical properties of polymer-drug conjugates. Various polymers, such as poly (ethylene glycol) (PEG), N-(2-hydroxypropyl) methacrylamide (HPMA), poly(glycolic acid) (PGA) and poly(lactide-co-glycolide) (PLGA) have been used successfully for clinical utilization from decades. These polymers are used in combination of drugs in such a manner that they target the specific tissues and thus the toxicity of drugs to other tissues is reduced. Presently, numerous polymer drug conjugates are under clinical trial for treatment of various diseases including cancer, diabetes, AIDS, rheumatoid arthritis etc. Many protein-polymer conjugates have been approved by FDA for clinical use but till date, no polymer-synthetic drug conjugate is approved by FDA, although many of them are undergoing final phase of clinical trials. This review highlights the recent advancements in the polymer-drug conjugates for treatment of various diseases and their preclinical and clinical status. PMID:26898741

  18. Advanced materials and nanotechnology for drug delivery.

    PubMed

    Yan, Li; Yang, Yang; Zhang, Wenjun; Chen, Xianfeng

    2014-08-20

    Many biological barriers are of great importance. For example, stratum corneum, the outmost layer of skin, effectively protects people from being invaded by external microorganisms such as bacteria and viruses. Cell membranes help organisms maintain homeostasis by controlling substances to enter and leave cells. However, on the other hand, these biological barriers seriously restrict drug delivery. For instance, stratum corneum has a very dense structure and only allows very small molecules with a molecular weight of below 500 Da to permeate whereas most drug molecules are much larger than that. A wide variety of drugs including genes needs to enter cells for proper functioning but cell membranes are not permeable to them. To overcome these biological barriers, many drug-delivery routes are being actively researched and developed. In this research news, we will focus on two advanced materials and nanotechnology approaches for delivering vaccines through the skin for painless and efficient immunization and transporting drug molecules to cross cell membranes for high-throughput intracellular delivery.

  19. Drugs for the treatment of peripheral neuropathies.

    PubMed

    Marmiroli, Paola; Cavaletti, Guido

    2016-01-01

    Peripheral neuropathies are frequent in association with systemic diseases as well as isolated disorders. Recent advances in the therapy of specific neuropathies led to the approval of new drugs/treatments. This review selected those peripheral neuropathies where the most recent approvals were provided and revised the potential future developments in diabetic and toxic-induced neuropathies, although they do not have a currently available causal therapy in view of their epidemiological and social relevance. Data have been extracted from the most important published trials and from clinical experience. In addition, data from the Food and Drug Administration and European Medicine Agency indications on the treatment of the selected peripheral neuropathies and from recently updated international guidelines have also been included. The website of the U.S. National Institutes of Health www.clinicaltrials.gov registry has been used as the reference database for phase III clinical trials not yet published or ongoing. This review gives a general overview of the most recent advances in the treatment of amyloid, inflammatory, and paraproteinemic peripheral neuropathies. Moreover, it briefly describes the unmet medical need in disabling and frequent conditions, such as diabetic and chemotherapy-induced neuropathy, highlighting the most promising therapeutic approaches to their treatment. PMID:26567516

  20. Drugs for the treatment of peripheral neuropathies.

    PubMed

    Marmiroli, Paola; Cavaletti, Guido

    2016-01-01

    Peripheral neuropathies are frequent in association with systemic diseases as well as isolated disorders. Recent advances in the therapy of specific neuropathies led to the approval of new drugs/treatments. This review selected those peripheral neuropathies where the most recent approvals were provided and revised the potential future developments in diabetic and toxic-induced neuropathies, although they do not have a currently available causal therapy in view of their epidemiological and social relevance. Data have been extracted from the most important published trials and from clinical experience. In addition, data from the Food and Drug Administration and European Medicine Agency indications on the treatment of the selected peripheral neuropathies and from recently updated international guidelines have also been included. The website of the U.S. National Institutes of Health www.clinicaltrials.gov registry has been used as the reference database for phase III clinical trials not yet published or ongoing. This review gives a general overview of the most recent advances in the treatment of amyloid, inflammatory, and paraproteinemic peripheral neuropathies. Moreover, it briefly describes the unmet medical need in disabling and frequent conditions, such as diabetic and chemotherapy-induced neuropathy, highlighting the most promising therapeutic approaches to their treatment.

  1. Surgical treatment of advanced melanoma.

    PubMed

    Hussussian, Christopher J

    2010-01-01

    Primary surgical treatment should be considered for patients with metastatic melanoma. Because of the poor response of melanoma to chemotherapy or radiation therapy, surgery can be the best approach to quickly eliminate detectable disease and return the patient to normal activities. In properly selected patients, surgery can lead to significant palliation and prolongation of survival. This article reviews the principles of patient selection and the potential benefits of surgical management of melanoma metastatic to various sites. Novel adjuvant therapies are being developed to augment the benefits of surgical treatment of advanced melanoma in the future.

  2. 40 CFR 35.2101 - Advanced treatment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  3. 40 CFR 35.2101 - Advanced treatment.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Advanced treatment. 35.2101 Section 35... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2101 Advanced treatment. Projects proposing advanced treatment shall be awarded grant assistance only after the project has...

  4. 40 CFR 35.2101 - Advanced treatment.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Advanced treatment. 35.2101 Section 35... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2101 Advanced treatment. Projects proposing advanced treatment shall be awarded grant assistance only after the project has...

  5. 40 CFR 35.2101 - Advanced treatment.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Advanced treatment. 35.2101 Section 35... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2101 Advanced treatment. Projects proposing advanced treatment shall be awarded grant assistance only after the project has...

  6. 40 CFR 35.2101 - Advanced treatment.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Advanced treatment. 35.2101 Section 35... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2101 Advanced treatment. Projects proposing advanced treatment shall be awarded grant assistance only after the project has...

  7. Advancing drug discovery: a pharmaceutics perspective.

    PubMed

    Kwong, Elizabeth

    2015-03-01

    Current industry perspective of how discovery is conducted seems to be fragmented and does not have a unified overall outlook of how discovery challenges are being addressed. Consequently, well-defined processes and drug-likeness criteria are being viewed as "broken" and will not maintain future R&D productivity. In this commentary, an analysis of existing practices for defining successful development candidates resulted in a 5 "must do" list to help advance Drug Discovery as presented from a Pharmaceutics perspective. The 5 "must do" list includes: what an ideal discovery team model should look like, what criteria should be considered for the desired development candidate profile, what the building blocks of the development candidate should look like, and how to assess the development risks of the candidate.

  8. Cutaneous melanoma: new advances in treatment*

    PubMed Central

    Foletto, Michele Ceolin; Haas, Sandra Elisa

    2014-01-01

    Cutaneous melanoma is a challenge to treat. Over the last 30 years, no drug or combination of drugs demonstrated significant impact to improve patient survival. From 1995 to 2000, the use of cytokines such as interferon and interleukin become treatment options. In 2011, new drugs were approved by the U.S. Food and Drug Administration, including peginterferon alfa-2b for patients with stage III disease, vemurafenib for patients with metastatic melanoma with the BRAF V600E mutation, and ipilimumab, a monoclonal antibody directed to the CTLA-4 T lymphocyte receptor, to combat metastatic melanoma in patients who do not have the BRAF V600E mutation. Both ipilimumab and vemurafenib showed results in terms of overall survival. Other trials with inhibitors of other genes, such as the KIT gene and MEK, are underway in the search for new discoveries. The discovery of new treatments for advanced or metastatic disease aims to relieve symptoms and improve patient quality of life. PMID:24770508

  9. Recent Advances in Drug Eluting Stents

    PubMed Central

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

    2013-01-01

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

  10. Audits for advanced treatment dosimetry

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

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

  11. Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment

    PubMed Central

    Bonanno, Laura; Zago, Giulia; Marulli, Giuseppe; Del Bianco, Paola; Schiavon, Marco; Pasello, Giulia; Polo, Valentina; Canova, Fabio; Tonetto, Fabrizio; Loreggian, Lucio; Rea, Federico; Conte, PierFranco; Favaretto, Adolfo

    2016-01-01

    Objectives If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs). No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. Methods We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1), paclitaxel (200 mg/m2, d1), and gemcitabine (1,000 mg/m2 d1, 8) for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS) and overall survival (OS) were correlated to response, surgery, and clinical features. Results In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors–7th edition staging system). A total of 36 (62%) patients achieved partial response (PR), and six (10%) progressions were recorded. Grade 3–4 hematological toxicity was observed in 36 (62%) cases. After chemotherapy, 37 (64%) patients underwent surgery followed by adjuvant radiotherapy, and two patients received radical-intent radiotherapy. The median PFS and OS were 11 months and 23 months, respectively. Both PFS and OS were significantly correlated to objective response (P<0.0001) and surgery (P<0.0001 and P=0.002). Patients obtaining PR and receiving local treatment achieved a median PFS and OS of 35 and 48 months, respectively. Median PFS and OS of patients not achieving PR or not receiving local treatment were 5–7 and 11–15 months, respectively. The extension of surgery did not affect the outcome. Conclusion The

  12. Treatment of advanced esophageal cancer

    SciTech Connect

    Kelsen, D.

    1982-12-01

    When radiation therapy is used for palliation of obstruction in patients with advanced esophageal carcinoma, an improvement in dysphagia can be expected in approximately 50% of patients. Major objective responses have rarely been quantitied but, in one study, were seen in 33% patients. Recurrence of dysphagia is usually seen within 2-6 months of treatment. Radiation toxicities and complications, even when used with palliative intent, can be substantial and include esophagitis, tracheoesophageal or esophageal-aortic fistula, mediastinitis, hemorrhage, pneumonitis, and myelosuppression. (JMT)

  13. Advances in Lymphatic Imaging and Drug Delivery

    SciTech Connect

    Nune, Satish K.; Gunda, Padmaja; Majeti, Bharat K.; Thallapally, Praveen K.; Laird, Forrest M.

    2011-09-10

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

  14. Recent treatment advances and novel therapeutic approaches in epilepsy

    PubMed Central

    Serrano, Enrique

    2015-01-01

    The purpose of this article is to review recent advances in the treatment of epilepsy. It includes five antiepileptic drugs that have been recently added to the pharmacologic armamentarium and surgical techniques that have been developed in the last few years. Finally, we review ongoing research that may have a potential role in future treatments of epilepsy. PMID:26097734

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

    PubMed

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

    2015-10-15

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

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

    PubMed Central

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

    2015-01-01

    Despite concerted efforts over the past 2 decades at developing new diagnostics, drugs, and vaccines with expanding pipelines, tuberculosis remains a global emergency. Several novel diagnostic technologies show promise of better point-of-care rapid tests for tuberculosis including nucleic acid–based amplification tests, imaging, and breath analysis of volatile organic compounds. Advances in new and repurposed drugs for use in multidrug-resistant (MDR) or extensively drug-resistant (XDR) tuberculosis have focused on development of several new drug regimens and their evaluation in clinical trials and now influence World Health Organization guidelines. Since the failure of the MVA85A vaccine 2 years ago, there have been no new tuberculosis vaccine candidates entering clinical testing. The current status quo of the lengthy treatment duration and poor treatment outcomes associated with MDR/XDR tuberculosis and with comorbidity of tuberculosis with human immunodeficiency virus and noncommunicable diseases is unacceptable. New innovations and political and funder commitment for early rapid diagnosis, shortening duration of therapy, improving treatment outcomes, and prevention are urgently required. PMID:26409271

  17. Pharmacogenetic Treatments for Drug Addiction

    PubMed Central

    Haile, Colin N.; Kosten, Thomas R.; Kosten, Therese A.

    2009-01-01

    Background Pharmacogenetics uses genetic variation to predict individual differences in response to medications and holds much promise to improve treatment of addictive disorders. Objectives To review how genetic variation affects responses to cocaine, amphetamine, and methamphetamine and how this information may guide pharmacotherapy. Methods We performed a cross-referenced literature search on pharmacogenetics, cocaine, amphetamine, and methamphetamine. Results We describe functional genetic variants for enzymes dopamine-beta-hydroxylase (DβH), catechol-O-methyltransferase (COMT), and dopamine transporter (DAT1), dopamine D4 receptor, and brain-derived neurotrophic factor (BDNF). A single nucleotide polymorphism (SNP; C-1021T) in the DβH gene is relevant to paranoia associated with disulfiram pharmacotherapy for cocaine addiction. Individuals with variable number tandem repeats (VNTR) of the SLC6A3 gene 3′-untranslated region polymorphism of DAT1 have altered responses to drugs. The 10/10 repeat respond poorly to methylphenidate pharmacotherapy and the 9/9 DAT1 variant show blunted euphoria and physiological response to amphetamine. COMT, D4 receptor, and BDNF polymorphisms are linked to methamphetamine abuse and psychosis. Conclusions Disulfiram and methylphenidate pharmacotherapies for cocaine addiction are optimized by considering polymorphisms affecting DβH and DAT1 respectively. Altered subjective effects for amphetamine in DAT1 VNTR variants suggest a ‘protected’ phenotype. Scientific Significance Pharmacogenetic-based treatments for psychostimulant addiction are critical for successful treatment. PMID:19462300

  18. Recent advances in antimultiple myeloma drug development

    PubMed Central

    Wang, Nuozhou; Bartlow, Patrick; Ouyang, Qin; Xie, Xiang-Qun

    2015-01-01

    Multiple myeloma (MM) is the second most common hematological malignancy and is characterized by the aberrant proliferation of terminally differentiated plasma B cells with impairment in apoptosis capacity. Particularly, osteolytic bone diseases and renal failure resulting from hyperparaproteinemia and hypercalcemia have been the major serious sequelae that are inextricably linked with MM tumor progression. Despite the introduction of new treatment regimens, problematic neuropathy, thrombocytopenia, drug resistance and high MM relapse rates continue to plague the current therapies. New chemical agents are in development on the basis of understanding several signaling pathways and molecular mechanisms like tumor necrosis factor-α, proteasome, PI3K and MARKs. This review focuses on the most recent patents and clinical trials in the development of new medicine for the treatment of multiple myeloma. Furthermore, the important signaling pathways involved in the proliferation, survival and apoptosis of myeloma cells will be discussed. PMID:24998287

  19. Diabetes Drug Victoza Might Not Help Advanced Heart Failure Patients

    MedlinePlus

    ... html Diabetes Drug Victoza Might Not Help Advanced Heart Failure Patients Study participants may have been too sick ... to improve heart function in patients with advanced heart failure, a new study finds. The theory for this ...

  20. Recent advances in flavivirus antiviral drug discovery and vaccine development.

    PubMed

    Ray, Debashish; Shi, Pei-Yong

    2006-01-01

    Many flaviviruses, including yellow fever virus, dengue virus, Japanese encephalitis virus, tick-borne encephalitis virus, and West Nile virus, are globally important human pathogens. Despite an emergence and resurgence of flavivirus-mediated disease, specific therapies are not yet available; however, significant progress has been made toward the prevention and treatment of flavivirus infections. In this article we review recent advances made in the areas of (i) flavivirus vaccine development, and (ii) antiflavivirus drug discovery reported in literature and patents, and highlight strategies used in these investigations. PMID:18221133

  1. Advanced drug delivery and targeting technologies for the ocular diseases

    PubMed Central

    Barar, Jaleh; Aghanejad, Ayuob; Fathi, Marziyeh; Omidi, Yadollah

    2016-01-01

    Introduction: Ocular targeted therapy has enormously been advanced by implementation of new methods of drug delivery and targeting using implantable drug delivery systems (DDSs) or devices (DDDs), stimuli-responsive advanced biomaterials, multimodal nanomedicines, cell therapy modalities and medical bioMEMs. These technologies tackle several ocular diseases such as inflammation-based diseases (e.g., scleritis, keratitis, uveitis, iritis, conjunctivitis, chorioretinitis, choroiditis, retinitis, retinochoroiditis), ocular hypertension and neuropathy, age-related macular degeneration and mucopolysaccharidosis (MPS) due to accumulation of glycosaminoglycans (GAGs). Such therapies appear to provide ultimate treatments, even though much more effective, yet biocompatible, noninvasive therapies are needed to control some disabling ocular diseases/disorders. Methods: In the current study, we have reviewed and discussed recent advancements on ocular targeted therapies. Results: On the ground that the pharmacokinetic and pharmacodynamic analyses of ophthalmic drugs need special techniques, most of ocular DDSs/devices developments have been designed to localized therapy within the eye. Application of advanced DDSs such as Subconjunctival insert/implants (e.g., latanoprost implant, Gamunex-C), episcleral implant (e.g., LX201), cationic emulsions (e.g., Cationorm™, Vekacia™, Cyclokat™), intac/punctal plug DDSs (latanoprost punctal plug delivery system, L-PPDS), and intravitreal implants (I-vitaion™, NT-501, NT- 503, MicroPump, Thethadur, IB-20089 Verisome™, Cortiject, DE-102, Retisert™, Iluvein™ and Ozurdex™) have significantly improved the treatment of ocular diseases. However, most of these DDSs/devices are applied invasively and even need surgical procedures. Of these, use of de novo technologies such as advanced stimuli-responsive nanomaterials, multimodal nanosystems (NSs)/nanoconjugates (NCs), biomacromolecualr scaffolds, and bioengineered cell therapies

  2. The Social Ecology of Drug Treatment.

    ERIC Educational Resources Information Center

    Murdock, Steve H.; And Others

    1980-01-01

    Evaluated perceptions of treatment environments within the Comprehensive Drug Program of Dade County (Miami) Florida. Analysis revealed that perceptions of drug clients toward their treatment environments were more positive than those of clients in other types of medical and psychiatric treatment. Perceptions varied directly with contact between…

  3. Treatment of advanced-stage Hodgkin lymphoma.

    PubMed

    Vassilakopoulos, Theodoros P; Johnson, Peter W M

    2016-07-01

    There is now good evidence that the escalated BEACOPP regimen (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone) is more effective in controlling advanced-stage Hodgkin lymphoma (HL) than the widely used ABVD regimen (adriamycin, bleomycin, vinblastine, dacarbazine), but the extra efficacy comes at the expense of both short- and long-term toxicity, and there is debate as to whether overall survival is affected. Baseline prognostic factors have proven of limited utility for determining which patients require more intensive therapy and recent studies have sought to use interim fluoro-deoxyglucose positron emission tomography (FDG-PET) evaluation as a means to guide the modulation of treatment, both upwards and downwards in intensity. These suggest that if treatment starts with ABVD then patients remaining PET-positive after 2 months can be salvaged with escalated BEACOPP in around 65% of cases, but those becoming PET-negative may still experience recurrences in 15%-20%, an event that is more common in those with more advanced disease at presentation. There are early data to suggest that starting with escalated BEACOPP may reduce the rate of recurrence after a negative interim PET to less than 10%. This may be an attractive approach for those with very high-risk features at presentation, but risks overtreating many patients if applied nonselectively. New regimens incorporating antibody-drug conjugates may shift the balance of efficacy and toxicity once again, and further studies are underway to evaluate this. PMID:27496308

  4. Drug Abuse Treatment in Prisons. Treatment Research Report.

    ERIC Educational Resources Information Center

    National Inst. for Advanced Studies, Washington, DC.

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

  5. Advances in anti-epileptic drug testing.

    PubMed

    Krasowski, Matthew D; McMillin, Gwendolyn A

    2014-09-25

    In the past twenty-one years, 17 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are clobazam, ezogabine (retigabine), eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. Therapeutic drug monitoring is often used in the clinical dosing of the newer anti-epileptic drugs. The drugs with the best justifications for drug monitoring are lamotrigine, levetiracetam, oxcarbazepine, stiripentol, and zonisamide. Perampanel, stiripentol and tiagabine are strongly bound to serum proteins and are candidates for monitoring of the free drug fractions. Alternative specimens for therapeutic drug monitoring are saliva and dried blood spots. Therapeutic drug monitoring of the new antiepileptic drugs is discussed here for managing patients with epilepsy. PMID:24925169

  6. Advances in tau-based drug discovery

    PubMed Central

    Noble, Wendy; Pooler, Amy M.; Hanger, Diane P.

    2011-01-01

    Introduction Tauopathies, including Alzheimer’s disease (AD) and some frontotemporal dementias, are neurodegenerative diseases characterised by pathological lesions comprised of tau protein. There is currently a significant and urgent unmet need for disease-modifying therapies for these conditions and recently attention has turned to tau as a potential target for intervention. Areas covered Increasing evidence has highlighted pathways associated with tau-mediated neurodegeneration as important targets for drug development. Here, the authors review recently published papers in this area and summarise the genetic and pharmacological approaches that have shown efficacy in reducing tau-associated neurodegeneration. These include the use of agents to prevent abnormal tau processing and increase tau clearance, therapies targeting the immune system, and the manipulation of tau pre-mRNA to modify tau isoform expression. Expert opinion Several small molecule tau-based treatments are currently being assessed in clinical trials, the outcomes of which are eagerly awaited. Current evidence suggests that therapies targeting tau are likely, at least in part, to form the basis of an effective and safe treatment for Alzheimer’s disease and related neurodegenerative disorders in which tau deposition is evident. PMID:22003359

  7. Enhancing Residential Treatment for Drug Court Participants

    ERIC Educational Resources Information Center

    Koob, Jeff; Brocato, Jo; Kleinpeter, Christine

    2011-01-01

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

  8. Drug Treatment as a Crime Fighting Tool.

    PubMed

    Jofre-Bonet, Mireia; Sindelar, Jody L.

    2001-12-01

    BACKGROUND: The primary approach to reducing crime in the US has been through the criminal justice system. However, drug treatment may be an effective tool in reducing crime. In order to make better use of treatment as an alternative approach, one needs to know if reducing drug use through treatment results in decreased crime. AIMS OF THE STUDY: The objective of this paper is to model and empirically investigate the extent to which a change in drug use that results from treatment reduces crime and whether a change in drug use is causally related to change in crime. We focus on crime-for-profit. METHODS: We use a multi-site dataset of 3,502 inner-city drug users entering treatment. We analyze the change in drug use and crime pre and post treatment. We take first differences to address the omitted variable problem. RESULTS: We find that treatment reduces drug use and that, in turn, reduced drug use has a significant impact on crime. For our study population, reduced drug use seems to be causally related to reduced crime. This finding is robust to specification and subsamples. We estimate that reduced drug use due to treatment is associated with 54% fewer days of crime for profit, ceteris paribus. DISCUSSION: We use a longitudinal data set and a novel approach to analyze the relationship between crime and drugs. We analyze a low-income, inner-city, drug-addicted sample. We use self-reported crime. For our purposes, the use of individual data is an improvement over the use of aggregate level data that has been used in much of the related literature. Limitations of our paper include that we do not have a random sample and that our measure is self-reported in the previous 30 days. IMPLICATIONS FOR HEALTH POLICIES: Our findings suggest that drug treatment may be an effective crime-fighting tool. Treatment reduces not only the crime of drug possession, but also crime-for-profit. Current public policy emphasizes use of the criminal justice system, incarceration in

  9. Drug treatments in criminal justice settings.

    PubMed

    Nordstrom, Benjamin R; Williams, A R

    2012-06-01

    The available evidence suggests that drug treatment can lead to modest, but real, reductions in criminal offending for drug-using criminal offenders. Considering the scope of the problem of drug-related crime and the expense of dealing with these issues, even marginal improvements can lead to important aggregate savings in both economic and humanitarian terms. More randomized, controlled trials of drug treatment in criminal justice programs will lead to a more sophisticated understanding of what kind of treatment works best for this group.

  10. [Vaccines for the treatment of drug addiction].

    PubMed

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

    2016-01-01

    The treatment of drug addiction is a very wide-ranging sector within modern medicine. The use of immunotherapy in this context represents an innovative approach. The purpose of this paper is to illustrate, through a literature review, the main avenues of research and the results obtained with immunotherapy in the treatment of drug addiction. PMID:27077562

  11. Recent advances in understanding hepatic drug transport

    PubMed Central

    Stieger, Bruno; Hagenbuch, Bruno

    2016-01-01

    Cells need to strictly control their internal milieu, a function which is performed by the plasma membrane. Selective passage of molecules across the plasma membrane is controlled by transport proteins. As the liver is the central organ for drug metabolism, hepatocytes are equipped with numerous drug transporters expressed at the plasma membrane. Drug disposition includes absorption, distribution, metabolism, and elimination of a drug and hence multiple passages of drugs and their metabolites across membranes. Consequently, understanding the exact mechanisms of drug transporters is essential both in drug development and in drug therapy. While many drug transporters are expressed in hepatocytes, and some of them are well characterized, several transporters have only recently been identified as new drug transporters. Novel powerful tools to deorphanize (drug) transporters are being applied and show promising results. Although a large set of tools are available for studying transport in vitro and in isolated cells, tools for studying transport in living organisms, including humans, are evolving now and rely predominantly on imaging techniques, e.g. positron emission tomography. Imaging is an area which, certainly in the near future, will provide important insights into "transporters at work" in vivo. PMID:27781095

  12. The drug treatment of premature ejaculation

    PubMed Central

    2016-01-01

    The management recommendation for both acquired premature ejaculation (APE) and lifelong PE (LPE) are similar, such as a behavioral/psychotherapy, a pharmacotherapy and a combination of these treatments. For the drug treatment for PE, gold standard is selective serotonin reuptake inhibitors (SSRIs) including dapoxetine or paroxetine. The drug treatment for PE is still developing and some new promising therapeutic options have been proposed. Topical anesthetics, tramadol, and alpha-1 blockers will be the next strategies of the drug treatment for PE in the future. PMID:27652221

  13. The drug treatment of premature ejaculation.

    PubMed

    Hisasue, Shin-Ichi

    2016-08-01

    The management recommendation for both acquired premature ejaculation (APE) and lifelong PE (LPE) are similar, such as a behavioral/psychotherapy, a pharmacotherapy and a combination of these treatments. For the drug treatment for PE, gold standard is selective serotonin reuptake inhibitors (SSRIs) including dapoxetine or paroxetine. The drug treatment for PE is still developing and some new promising therapeutic options have been proposed. Topical anesthetics, tramadol, and alpha-1 blockers will be the next strategies of the drug treatment for PE in the future. PMID:27652221

  14. The drug treatment of premature ejaculation

    PubMed Central

    2016-01-01

    The management recommendation for both acquired premature ejaculation (APE) and lifelong PE (LPE) are similar, such as a behavioral/psychotherapy, a pharmacotherapy and a combination of these treatments. For the drug treatment for PE, gold standard is selective serotonin reuptake inhibitors (SSRIs) including dapoxetine or paroxetine. The drug treatment for PE is still developing and some new promising therapeutic options have been proposed. Topical anesthetics, tramadol, and alpha-1 blockers will be the next strategies of the drug treatment for PE in the future.

  15. Treatment Approaches for Drug Addiction

    MedlinePlus

    ... Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine ... Scientists are developing other medications to treat stimulant (cocaine, methamphetamine) and cannabis (marijuana) addiction. People who use ...

  16. Recent advances in ocular drug delivery.

    PubMed

    Achouri, Djamila; Alhanout, Kamel; Piccerelle, Philippe; Andrieu, Véronique

    2013-11-01

    Amongst the various routes of drug delivery, the field of ocular drug delivery is one of the most interesting and challenging endeavors facing the pharmaceutical scientist. Recent research has focused on the characteristic advantages and limitations of the various drug delivery systems, and further research will be required before the ideal system can be developed. Administration of drugs to the ocular region with conventional delivery systems leads to short contact time of the formulations on the epithelium and fast elimination of drugs. This transient residence time involves poor bioavailability of drugs which can be explained by the tear production, non-productive absorption and impermeability of corneal epithelium. Anatomy of the eye is shortly presented and is connected with ophthalmic delivery and bioavailability of drugs. In the present update on ocular dosage forms, chemical delivery systems such as prodrugs, the use of cyclodextrins to increase solubility of various drugs, the concept of penetration enhancers and other ocular drug delivery systems such as polymeric gels, bioadhesive hydrogels, in-situ forming gels with temperature-, pH-, or osmotically induced gelation, combination of polymers and colloidal systems such as liposomes, niosomes, cubosomes, microemulsions, nanoemulsions and nanoparticles are discussed. Novel ophthalmic delivery systems propose the use of many excipients to increase the viscosity or the bioadhesion of the product. New formulations like gels or colloidal systems have been tested with numerous active substances by in vitro and in vivo studies. Sustained drug release and increase in drug bioavailability have been obtained, offering the promise of innovation in drug delivery systems for ocular administration. Combining different properties of pharmaceutical formulations appears to offer a genuine synergy in bioavailability and sustained release. Promising results are obtained with colloidal systems which present very comfortable

  17. Drug-Hypersensitivity Syndrome: Diagnosis and Treatment

    PubMed Central

    Hamm, Rose L.

    2012-01-01

    Drug-induced hypersensitivity syndrome is a systemic autoimmune disorder that results in mucocutaneous symptoms ranging in severity from mild pruritus to life-threatening skin and mucosal loss, with different nomenclature depending on the severity of the symptoms. The purpose of this article is to review the recent advances in understanding the pathology of drug-induced hypersensitivity syndrome, as well as current recommendations for both medical and wound management. PMID:24527369

  18. Drug abuse treatment as AIDS prevention.

    PubMed Central

    Metzger, D S; Navaline, H; Woody, G E

    1998-01-01

    OBJECTIVE: As the acquired immunodeficiency syndrome (AIDS) epidemic among drug users enters its third decade in the United States, it is important to consider the role playing by substance abuse treatment in the prevention of human immunodeficiency virus (HIV) infection. METHODS: The authors review the research literature, examining findings from studies with behavioral and serologic measures on the association among treatment participation, HIV risk reduction, and HIV infection. RESULTS: Numerous studies have now documented that significantly lower rates of drug use and related risk behaviors are practiced by injecting drug users (IDUs) who are in treatment. Importantly, these behavioral differences, based primarily on self-report, are consistent with studies that have examined HIV seroprevalence and seroincidence among drug users. CONCLUSION: The underlying mechanism of action suggested by the collective findings of the available literature is rather simple-- individuals who enter and remain in treatment reduce their drug use, when leads to fewer instances of drug-related risk behavior. This lower rate of exposure results in fewer infections with HIV. The protective effects of treatment, however, can only be achieved when programs are accessible and responsive to the changing needs of drug users. Future research needs to be directed at developing a better understanding of the factors that enhance treatment entry and retention. PMID:9722815

  19. Methodological advances in drug discovery for Chagas disease

    PubMed Central

    Bustamante, Juan M.; Tarleton, Rick L.

    2011-01-01

    Introduction Chagas disease is the highest impact human infectious disease in Latin America, and the leading worldwide cause of myocarditis. Despite the availability of several compounds that have demonstrated efficacy in limiting the effects of T. cruzi, these compounds are rarely used due to their variable efficacy, substantial side effects and the lack of methodologies for confirming their effectiveness. Furthermore, the development of more efficacious compounds is challenged by limitations of systems for assessing drug efficacy in vitro and in vivo. Areas covered Herein, the authors review the development of Chagas disease drug discovery methodology, focusing on recent developments in high throughput screening, in vivo testing methods and assessments of efficacy in humans. Particularly, this review documents the significant progress that has taken place over the last 5 years that have paved the way for both target-focused and high-throughput screens of compound libraries. Expert opinion The tools for in vitro and in vivo screening of anti-T. cruzi compounds have improved dramatically in the last few years and there are now a number of excellent in vivo testing models available; this somewhat alleviates the bottleneck issue of quickly and definitively demonstrating in vivo efficacy in a relevant host animal system. These advances emphasize the potential for additional progress resulting in new treatments for Chagas disease in the coming years. That being said, national and international agencies must improve the coordination of research and development efforts in addition to cultivating the funding sources for the development of these new treatments. PMID:21712965

  20. NASA Bioreactors Advance Disease Treatments

    NASA Technical Reports Server (NTRS)

    2009-01-01

    the body. Experiments conducted by Johnson scientist Dr. Thomas Goodwin proved that the NASA bioreactor could successfully cultivate cells using simulated microgravity, resulting in three-dimensional tissues that more closely approximate those in the body. Further experiments conducted on space shuttle missions and by Wolf as an astronaut on the Mir space station demonstrated that the bioreactor s effects were even further expanded in space, resulting in remarkable levels of tissue formation. While the bioreactor may one day culture red blood cells for injured astronauts or single-celled organisms like algae as food or oxygen producers for a Mars colony, the technology s cell growth capability offers significant opportunities for terrestrial medical research right now. A small Texas company is taking advantage of the NASA technology to advance promising treatment applications for diseases both common and obscure.

  1. [Drug treatment of functional psychotic disorders].

    PubMed

    Bridler, R; Umbricht, D; Hell, D

    2001-05-31

    Psychotic symptoms occur in different psychiatric disorders. The principles of antipsychotic drug treatment of various non-organic psychotic disorders are discussed. In particular, the role of the so-called atypical antipsychotics is highlighted. PMID:11450186

  2. Advancing drug availability-experiences from Africa.

    PubMed

    Powell, Richard A; Kaye, Richard Mugula; Ddungu, Henry; Mwangi-Powell, Faith

    2010-07-01

    International health and drug regulatory authorities acknowledge that analgesics (especially opioids) are insufficiently available for pain management in many countries. In Africa, reported morphine consumption is far below the global mean, with multiple factors hampering opioid supply. Since 2006, the African Palliative Care Association has hosted three regional drug availability workshops across the continent to address this issue. Using an interactive format, the workshops have identified country-specific barriers to opioid and other essential medication accessibility before supporting participants to develop action plans to address recognized impediments. Despite multiple challenges, a number of successes have arisen from the implementation of the plans. However, key issues remain, including the introduction of supportive policy environments, effective educational initiatives, and measures to address supply-chain obstacles impeding drug availability. PMID:20619205

  3. Sustainability assessment of advanced wastewater treatment technologies.

    PubMed

    Høibye, L; Clauson-Kaas, J; Wenzel, H; Larsen, H F; Jacobsen, B N; Dalgaard, O

    2008-01-01

    As a consequence of the EU Water Framework Directive more focus is now on discharges of hazardous substances from wastewater treatment plants and sewers. Thus, many municipalities in Denmark may have to adopt to future advanced treatment technologies. This paper describes a holistic assessment, which includes technical, economical and environmental aspects. The technical and economical assessment is performed on 5 advanced treatment technologies: sand filtration, ozone treatment, UV exclusively for disinfection of pathogenic microorganisms, membrane bioreactor (MBR) and UV in combination with advanced oxidation. The technical assessment is based on 12 hazardous substances comprising heavy metals, organic pollutants, endocrine disruptors as well as pathogenic microorganisms. The environmental assessment is performed by life cycle assessment (LCA) comprising 9 of the specific hazardous substances and three advanced treatment methods; sand filtration, ozone treatment and MBR. The technical and economic assessment showed that UV solely for disinfection purposes or ozone treatment is the most advantageous advanced treatment methods if the demands are restricted to pathogenic microorganisms. In terms of sustainability, sand filtration is the most advantageous method based on the technical and environmental assessment due to the low energy consumption and high efficiency with regards to removal of heavy metals.

  4. Seeking Drug Abuse Treatment: Know What to Ask

    MedlinePlus

    ... Abuse Treatment: Know What To Ask » Introduction Seeking Drug Abuse Treatment: Know What To Ask Email Facebook Twitter Introduction The goal of drug abuse treatment is to stop drug use and allow ...

  5. Newer drug treatment in dermatology.

    PubMed

    REES, R B; BENNETT, J H; GREENLEE, M R

    1959-07-01

    This article deals with a number of newer drugs now being employed in dermatology. The great beneficial role of corticoids both topically and systematically for various inflammatory dermatoses is now amply proved. The addition of a corticoid to a conventional acne lotion renders it much more effective. Nystatin for monilial infections is especially effective in a powder form. For systemic use Griseovulvin, now becoming available, is the most interesting current development in dermatology. Presumably, it is highly effective against ringworm of the hair, nails and skin. The role of synthetic antimalarials in treating chronic discoid lupus erythematosus and light sensitivity eruptions also is firmly established.

  6. Advances in text analytics for drug discovery.

    PubMed

    Roberts, Phoebe M; Hayes, William S

    2005-05-01

    The automated extraction of biological and chemical information has improved over the past year, with advances in access to content, entity extraction of genes, chemicals, kinetic data and relationships, and algorithms for generating and testing hypotheses. As the systems for reading and understanding scientific literature grow more powerful, so must the infrastructure in which to assemble information. Advances in infrastructure systems are discussed in this review. Research efforts have flourished as a result of text analytics competitions that attract participants from various disciplines, from computer science to bioinformatics.

  7. Drug treatment in precocious puberty.

    PubMed

    Wheeler, M D; Styne, D M

    1991-05-01

    Precocious puberty, as defined by the onset of pubertal development before the age of 8 years in girls or 9 years in boys, can be classified into central and peripheral aetiologies. Central precocious puberty (CPP) results from early activation of the hypothalamic-pituitary-gonadal axis and has similar physical and hormonal characteristics to normal puberty. Extrapituitary gonadotrophin secretion or independent sex steroid secretion results in peripheral precocious puberty (PPP). Precocious puberty is characterised by rapid growth and advancement of skeletal age. The skeletal advancement is greater than the growth increase, so that final adult height is compromised. Long-acting gonadotrophin releasing hormone (GnRH) agonists are the current therapy of choice for central precocious puberty, having demonstrated effectiveness in halting the precocious development associated with this condition with minimal side effects. GnRH agonists are not effective as therapy for peripheral precocious puberty, but a number of other agents have been used with some success. These include androgen antagonists, testolactone, ketoconazole, and medroxyprogesterone acetate. The use of GnRH agonists has been associated with an increase in predictions of final height; however, continuing studies in treated cohorts are necessary to determine the true benefit of any of these agents on increasing ultimate height.

  8. Recent advances in chitosan-based nanoparticulate pulmonary drug delivery.

    PubMed

    Islam, Nazrul; Ferro, Vito

    2016-08-14

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

  9. Recent advances in chitosan-based nanoparticulate pulmonary drug delivery

    NASA Astrophysics Data System (ADS)

    Islam, Nazrul; Ferro, Vito

    2016-07-01

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

  10. Advanced gastric cancer: Current treatment landscape and future perspectives

    PubMed Central

    Digklia, Antonia; Wagner, Anna Dorothea

    2016-01-01

    Gastric cancer currently ranks fourth in cancer-related mortality worldwide. In the western world, it is most often diagnosed at an advanced stage, after becoming metastatic at distant sites. Patients with advanced disease (locally advanced or metastatic) have a somber prognosis, with a median overall survival of 10-12 mo, and palliative chemotherapy is the mainstay of treatment. In recent years, novel approaches using inhibition of human epidermal growth factor receptor 2 (HER2) have demonstrated significant improvements in progression-free and overall survival, compared with chemotherapy alone, in first-line treatment of patients with overexpression of HER2. In addition, both second-line chemotherapy and treatment with the vascular endothelial growth factor receptor-inhibitor ramucirumab demonstrated significant benefits in terms of overall survival, compared with best supportive care, in randomized studies. Moreover, ramucirumab in combination with chemotherapy demonstrated further significant benefits in terms of progression-free and overall survival, compared with chemotherapy alone, in second-line treatment for patients with metastatic gastric cancer. A recently published molecular classification of gastric cancer is expected to improve patient stratification and selection for clinical trials and provide a roadmap for future drug development. Nevertheless, despite these developments the prognosis of patients with advanced gastric cancer remains poor. In this review we discuss current standards of care and outline major topics of drug development in gastric cancer. PMID:26937129

  11. Advances in the treatment of central serous chorioretinopathy

    PubMed Central

    Abouammoh, Marwan A.

    2015-01-01

    Central serous chorioretinopathy is a disease that is partly understood. Novel advancements have led to further understanding of the disease, and have identified choroidal dysfunction as the principal element in CSCR development. New imaging tools have aided in better monitoring disease response to various treatment models. Enhanced depth imaging optical coherence tomography, in particular, has helped in observing choroidal thickness changes after various treatment models. To date, photodynamic therapy and focal laser remain the main stay of treatment. More understanding of disease pathophysiology in the future will help in determining the drug of choice and the best management option for such cases. PMID:26586979

  12. Advanced research on dopamine signaling to develop drugs for the treatment of mental disorders: Ser311Cys polymorphisms of the dopamine D2-receptor gene and schizophrenia.

    PubMed

    Itokawa, Masanari; Arinami, Tadao; Toru, Michio

    2010-01-01

    Schizophrenia is a debilitating and complex mental disorder with a prevalence of approximately 1% worldwide. The etiology remains unclear, despite massive research efforts. Hyperactive dopaminergic signal transduction in the central nervous system is suggested to be involved in the pathophysiology of schizophrenia (the dopamine hypothesis). The dopamine D(2)-receptor (DRD2) gene is thus a promising candidate for associations with risk of schizophrenia. We investigated DRD2 and found a novel missense nucleotide change causing an amino acid substitution of serine with cysteine at codon 311 (Ser311Cys). We performed an association study using 156 schizophrenia patients and 300 controls. Cys311 in DRD2 was significantly associated with schizophrenia. Patients with the Cys311 allele displayed shorter duration of hospitalization and less severe negative symptoms and were more frequently married compared to patients without this allele, suggesting good response to treatment. We expanded samples to 291 patients with schizophrenia (including 11 postmortem brain samples), 579 controls, and 78 patients with affective disorders in a further case-control study. Cys311 was associated with schizophrenia, particularly in patients without negative symptoms, and bipolar disorder with mood-incongruent psychotic symptoms. Three meta-analyses using over 20 published studies confirmed the association. In vitro studies showed that Cys311-type D(2) receptor impairs dopamine-induced sequestration, which appears to be consistent with the dopamine hypothesis.

  13. Advances in the diagnosis and treatment of sarcoidosis

    PubMed Central

    2014-01-01

    This manuscript outlines recent advances in the diagnosis and treatment of sarcoidosis. The diagnosis of sarcoidosis can occasionally be made on clinical grounds without a confirmatory biopsy when very specific clinical findings are present. Otherwise, the diagnosis requires histologic evidence of granulomatous inflammation, exclusion of alternative causes, and evidence of systemic disease. Because there is no available diagnostic test for sarcoidosis, the diagnosis is never completely secure. Instruments have been developed to establish the presence of sarcoidosis in a second organ and hence establish the systemic nature of the disease. Corticosteroids remain the drug of choice for the treatment of sarcoidosis. Additional sarcoidosis medications are most commonly used as corticosteroid-sparing agents. Recent clinical sarcoidosis drug trials have exposed important issues that may confound trial results, including selecting patients with active disease, identifying study drug effects in patients receiving concomitant corticosteroids, and establishing proper study endpoints. PMID:25374667

  14. Recent advances in treatment of heart failure

    PubMed Central

    Kitai, Takeshi; Tang, WH Wilson

    2015-01-01

    With the total cases and economic burden of heart failure continuing to rise, there is an overwhelming need for novel therapies. Several drugs for heart failure have succeeded in preclinical and early-phase clinical trials, but most of them failed to show the real benefit in pivotal clinical trials. Meanwhile, the US Food and Drug Administration recently approved two promising new drugs to treat heart failure: ivabradine and sacubitril/valsartan. Furthermore, some of the newer agents in testing offer the potential for significant progress in addition to these drugs. Patiromer and zirconium cyclosilicate are attractive agents that are expected to prevent hyperkalemia during renin-angiotensin-aldosterone system inhibition, and serelaxin and urodilatin are promising drugs in the treatment of acute heart failure. Future clinical trials with more appropriate study designs, optimal clinical endpoints, and proper patient selection are mandatory to assess the true efficacy of these attractive compounds in clinical practice. PMID:26918130

  15. Drug-resistant tuberculosis: emerging treatment options

    PubMed Central

    Adhvaryu, Meghna; Vakharia, Bhasker

    2011-01-01

    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 drugsusceptible 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 markers for adequacy of treatment and an integrative approach to fulfill WHO goals. However, regulatory control over the drug market, as well as public-private partnership to use health program facilities to track patients and ensure

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

    PubMed

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

    2016-11-01

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

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

    PubMed

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

    2016-11-01

    Atopic dermatitis (AD) is a chronically relapsing skin inflammatory disorder characterized by perivascular infiltration of immunoglobulin-E (IgE), T-lymphocytes and mast cells. The key pathophysiological factors causing this disease are immunological disorders and the compromised epidermal barrier integrity. Pruritus, intense itching, psychological stress, deprived physical and mental performance and sleep disturbance are the hallmark features of this dermatological complication. Preventive interventions which include educational programs, avoidance of allergens, exclusive care towards skin, and the rational selection of therapeutic regimen play key roles in the treatment of dermatosis. In last two decades, it is evident from a plethora of studies that scientific focus is being driven from conventional therapies to the advanced nanocarrier-based regimen for an effective management of AD. These nanocarriers which include polymeric nanoparticles (NPs), hydrogel NPs, liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanoemulsion, provide efficient roles for the target specific delivery of the therapeutic payload. The success of these targeted therapies is due to their pharmaceutical versatility, longer retention time at the target site, avoiding off-target effects and preventing premature degradation of the incorporated drugs. The present review was therefore aimed to summarise convincing evidence for the therapeutic superiority of advanced nanocarrier-mediated strategies over the conventional therapies used in the treatment of AD. PMID:27592075

  18. Recent advances in antidepressant drug therapy.

    PubMed

    Quasim, M; Kumar, A

    1999-01-01

    Many new antidepressants are available for use. The acute effects of administration are mainly manifested as side-effects, whereas the chronic effects take 2-3 weeks to set in and are responsible for therapeutic action. Such changes may include formation and release of neurotransmitters, changes in pre-synaptic uptake, and changes in receptor density and sensitivity. The noradrenergic and serotonergic systems are not separate, but are entwined with each other. The newer SSRI citalopram, and drugs from the SNRI, NaSSA and NAN classes, have been shown in controlled trials to be equivalent to, or more efficacious than, TCAs and/or SSRIs. They have an improved side-effect profile, especially when compared to TCAs, and hence are better tolerated. PMID:24945062

  19. New Targeted Treatment May Slow Disease in Patients with Advanced GIST

    Cancer.gov

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

  20. Quantitative EEG Brain Mapping In Psychotropic Drug Development, Drug Treatment Selection, and Monitoring.

    PubMed

    Itil, Turan M.; Itil, Kurt Z.

    1995-05-01

    Quantification of standard electroencephalogram (EEG) by digital computers [computer-analyzed EEG (CEEG)] has transformed the subjective analog EEG into an objective scientific method. Until a few years ago, CEEG was only used to assist in the development of psychotropic drugs by means of the quantitative pharmaco EEG. Thanks to the computer revolution and the accompanying reductions in cost of quantification, CEEG can now also be applied in psychiatric practice. CEEG can assist the physician in confirming clinical diagnoses, selecting psychotropic drugs for treatment, and drug treatment monitoring. Advancements in communications technology allow physicians and researchers to reduce the costs of acquiring a high-technology CEEG brain mapping system by utilizing the more economical telephonic services. PMID:11850678

  1. Quantitative EEG Brain Mapping In Psychotropic Drug Development, Drug Treatment Selection, and Monitoring.

    PubMed

    Itil, Turan M.; Itil, Kurt Z.

    1995-05-01

    Quantification of standard electroencephalogram (EEG) by digital computers [computer-analyzed EEG (CEEG)] has transformed the subjective analog EEG into an objective scientific method. Until a few years ago, CEEG was only used to assist in the development of psychotropic drugs by means of the quantitative pharmaco EEG. Thanks to the computer revolution and the accompanying reductions in cost of quantification, CEEG can now also be applied in psychiatric practice. CEEG can assist the physician in confirming clinical diagnoses, selecting psychotropic drugs for treatment, and drug treatment monitoring. Advancements in communications technology allow physicians and researchers to reduce the costs of acquiring a high-technology CEEG brain mapping system by utilizing the more economical telephonic services.

  2. Asthma: pathogenesis and novel drugs for treatment.

    PubMed

    Olin, J Tod; Wechsler, Michael E

    2014-01-01

    Asthma affects almost 20 million people in the United States and more than 300 million people worldwide. Of these, 10-15% have severe asthma, which is refractory to commonly available drugs. New drugs are needed because those that are currently available cannot control symptoms and exacerbations in all patients and can cause adverse reactions. In the past 10 years, there have been substantial advances in the understanding of asthma genetics, airway biology, and immune cell signaling. These advances have led to the development of small molecule therapeutics and biologic agents that may improve asthma care in the future. Several new classes of asthma drugs--including ultra long acting β agonists and modulators of the interleukin 4 (IL-4), IL-5, IL-13, and IL-17 pathways--have been evaluated in randomized controlled trials. Other new drug classes--including dissociated corticosteroids, CXC chemokine receptor 2 antagonists, toll-like receptor 9 agonists, and tyrosine kinase inhibitors--remain in earlier phases of development. Despite some preliminary efficacy data, there is insufficient evidence to make strong recommendations about the use of these newer agents. Future research on the clinical efficacy of these biologic agents, the effect of newer agents on severe asthma in pediatric patients, and the biology of non-eosinophilic and corticosteroid resistant asthma is needed to reduce the morbidity of asthma worldwide. PMID:25420994

  3. Repurposing drugs for the treatment and control of helminth infections

    PubMed Central

    Panic, Gordana; Duthaler, Urs; Speich, Benjamin; Keiser, Jennifer

    2014-01-01

    Helminth infections are responsible for a considerable public health burden, yet the current drug armamentarium is small. Given the high cost of drug discovery and development, the high failure rates and the long duration to develop novel treatments, drug repurposing circumvents these obstacles by finding new uses for compounds other than those they were initially intended to treat. In the present review, we summarize in vivo and clinical trial findings testing clinical candidates and marketed drugs against schistosomes, food-borne trematodes, soil-transmitted helminths, Strongyloides stercoralis, the major human filariases lymphatic filariasis and onchocerciasis, taeniasis, neurocysticercosis and echinococcosis. While expanding the applications of broad-spectrum or veterinary anthelmintics continues to fuel alternative treatment options, antimalarials, antibiotics, antiprotozoals and anticancer agents appear to be producing fruitful results as well. The trematodes and nematodes continue to be most investigated, while cestodal drug discovery will need to be accelerated. The most clinically advanced drug candidates include the artemisinins and mefloquine against schistosomiasis, tribendimidine against liver flukes, oxantel pamoate against trichuriasis, and doxycycline against filariasis. Preclinical studies indicate a handful of promising future candidates, and are beginning to elucidate the broad-spectrum activity of some currently used anthelmintics. Challenges and opportunities are further discussed. PMID:25516827

  4. Polymeric drugs: Advances in the development of pharmacologically active polymers.

    PubMed

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

    2015-12-10

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

  5. Porous silicon advances in drug delivery and immunotherapy

    PubMed Central

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

    2013-01-01

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

  6. [Treatment approaches for synthetic drug addiction].

    PubMed

    Kobayashi, Ohji

    2015-09-01

    In Japan, synthetic drugs have emerged since late 2000s, and cases of emergency visits and fatal traffic accidents due to acute intoxication have rapidly increased. The synthetic drugs gained popularity mainly because they were cheap and thought to be "legal". The Japanese government restricted not only production and distribution, but also its possession and use in April 2014. As the synthetic drug dependent patients have better social profiles compared to methamphetamine abusers, this legal sanction may have triggered the decrease in the number of synthetic drug dependent patient visits observed at Kanagawa Psychiatric Center since July 2014. Treatment of the synthetic drug dependent patients should begin with empathic inquiry into the motives and positive psychological effects of the drug use. In the maintenance phase, training patients to trust others and express their hidden negative emotions through verbal communications is essential. The recovery is a process of understanding the relationship between psychological isolation and drug abuse, and gaining trust in others to cope with negative emotions that the patients inevitably would face in their subsequent lives. PMID:26394511

  7. Computational and experimental advances in drug repositioning for accelerated therapeutic stratification.

    PubMed

    Shameer, Khader; Readhead, Ben; Dudley, Joel T

    2015-01-01

    Drug repositioning is an important component of therapeutic stratification in the precision medicine paradigm. Molecular profiling and more sophisticated analysis of longitudinal clinical data are refining definitions of human diseases, creating needs and opportunities to re-target or reposition approved drugs for alternative indications. Drug repositioning studies have demonstrated success in complex diseases requiring improved therapeutic interventions as well as orphan diseases without any known treatments. An increasing collection of available computational and experimental methods that leverage molecular and clinical data enable diverse drug repositioning strategies. Integration of translational bioinformatics resources, statistical methods, chemoinformatics tools and experimental techniques (including medicinal chemistry techniques) can enable the rapid application of drug repositioning on an increasingly broad scale. Efficient tools are now available for systematic drug-repositioning methods using large repositories of compounds with biological activities. Medicinal chemists along with other translational researchers can play a key role in various aspects of drug repositioning. In this review article, we briefly summarize the history of drug repositioning, explain concepts behind drug repositioning methods, discuss recent computational and experimental advances and highlight available open access resources for effective drug repositioning investigations. We also discuss recent approaches in utilizing electronic health record for outcome assessment of drug repositioning and future avenues of drug repositioning in the light of targeting disease comorbidities, underserved patient communities, individualized medicine and socioeconomic impact.

  8. Advanced Therapeutic Strategies for Chronic Lung Disease Using Nanoparticle-Based Drug Delivery.

    PubMed

    Yhee, Ji Young; Im, Jintaek; Nho, Richard Seonghun

    2016-01-01

    Chronic lung diseases include a variety of obstinate and fatal diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), and lung cancers. Pharmacotherapy is important for the treatment of chronic lung diseases, and current progress in nanoparticles offers great potential as an advanced strategy for drug delivery. Based on their biophysical properties, nanoparticles have shown improved pharmacokinetics of therapeutics and controlled drug delivery, gaining great attention. Herein, we will review the nanoparticle-based drug delivery system for the treatment of chronic lung diseases. Various types of nanoparticles will be introduced, and recent innovative efforts to utilize the nanoparticles as novel drug carriers for the effective treatment of chronic lung diseases will also be discussed. PMID:27657144

  9. Advanced Therapeutic Strategies for Chronic Lung Disease Using Nanoparticle-Based Drug Delivery

    PubMed Central

    Yhee, Ji Young; Im, Jintaek; Nho, Richard Seonghun

    2016-01-01

    Chronic lung diseases include a variety of obstinate and fatal diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), and lung cancers. Pharmacotherapy is important for the treatment of chronic lung diseases, and current progress in nanoparticles offers great potential as an advanced strategy for drug delivery. Based on their biophysical properties, nanoparticles have shown improved pharmacokinetics of therapeutics and controlled drug delivery, gaining great attention. Herein, we will review the nanoparticle-based drug delivery system for the treatment of chronic lung diseases. Various types of nanoparticles will be introduced, and recent innovative efforts to utilize the nanoparticles as novel drug carriers for the effective treatment of chronic lung diseases will also be discussed. PMID:27657144

  10. The drug treatment of delayed ejaculation.

    PubMed

    Abdel-Hamid, Ibrahim A; Elsaied, Moustafa A; Mostafa, Taymour

    2016-08-01

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

  11. The drug treatment of delayed ejaculation

    PubMed Central

    Elsaied, Moustafa A.; Mostafa, Taymour

    2016-01-01

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

  12. The drug treatment of delayed ejaculation

    PubMed Central

    Elsaied, Moustafa A.; Mostafa, Taymour

    2016-01-01

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

  13. [Multidisciplinary treatment of locally advanced rectal cancer].

    PubMed

    Faes, Seraina; Gié, Olivier; Demartines, Nicolas; Hahnloser, Dieter

    2016-06-15

    Treatment of patients with locally advanced rectal cancer remains challenging. Preoperative imaging with pelvic MRI allows to identify patients for multimodal treatment including induction chemothe- rapy or neoadjuvant radio-chemotherapy and an extended surgical resection. With multidisciplinary approach and an experienced team, excellent oncologic results may be achieved, as well as a good function and quality of life, even with preservation of the anus in the majority of patients. PMID:27487624

  14. Advances in Nuclear Magnetic Resonance for Drug Discovery.

    PubMed

    Powers, Robert

    2009-10-01

    BACKGROUND: Drug discovery is a complex and unpredictable endeavor with a high failure rate. Current trends in the pharmaceutical industry have exasperated these challenges and are contributing to the dramatic decline in productivity observed over the last decade. The industrialization of science by forcing the drug discovery process to adhere to assembly-line protocols is imposing unnecessary restrictions, such as short project time-lines. Recent advances in nuclear magnetic resonance are responding to these self-imposed limitations and are providing opportunities to increase the success rate of drug discovery. OBJECTIVE/METHOD: A review of recent advancements in NMR technology that have the potential of significantly impacting and benefiting the drug discovery process will be presented. These include fast NMR data collection protocols and high-throughput protein structure determination, rapid protein-ligand co-structure determination, lead discovery using fragment-based NMR affinity screens, NMR metabolomics to monitor in vivo efficacy and toxicity for lead compounds, and the identification of new therapeutic targets through the functional annotation of proteins by FAST-NMR. CONCLUSION: NMR is a critical component of the drug discovery process, where the versatility of the technique enables it to continually expand and evolve its role. NMR is expected to maintain this growth over the next decade with advancements in automation, speed of structure calculation, in-cell imaging techniques, and the expansion of NMR amenable targets.

  15. Advances in Nuclear Magnetic Resonance for Drug Discovery

    PubMed Central

    Powers, Robert

    2010-01-01

    Background Drug discovery is a complex and unpredictable endeavor with a high failure rate. Current trends in the pharmaceutical industry have exasperated these challenges and are contributing to the dramatic decline in productivity observed over the last decade. The industrialization of science by forcing the drug discovery process to adhere to assembly-line protocols is imposing unnecessary restrictions, such as short project time-lines. Recent advances in nuclear magnetic resonance are responding to these self-imposed limitations and are providing opportunities to increase the success rate of drug discovery. Objective/Method A review of recent advancements in NMR technology that have the potential of significantly impacting and benefiting the drug discovery process will be presented. These include fast NMR data collection protocols and high-throughput protein structure determination, rapid protein-ligand co-structure determination, lead discovery using fragment-based NMR affinity screens, NMR metabolomics to monitor in vivo efficacy and toxicity for lead compounds, and the identification of new therapeutic targets through the functional annotation of proteins by FAST-NMR. Conclusion NMR is a critical component of the drug discovery process, where the versatility of the technique enables it to continually expand and evolve its role. NMR is expected to maintain this growth over the next decade with advancements in automation, speed of structure calculation, in-cell imaging techniques, and the expansion of NMR amenable targets. PMID:20333269

  16. Advances in Adolescent Substance Abuse Treatment

    PubMed Central

    Botzet, Andria M.; Fahnhorst, Tamara

    2011-01-01

    Alcohol and other drug use among adolescents has been a public health problem for decades. Although some substance use may be developmentally routine, a concerning number of adolescents meet criteria for a substance use disorder and could greatly benefit from a quality treatment experience. However, parents and health care providers want evidence of the efficacy of adolescent-specific treatment programs. This review summarizes four factors surrounding the efficacy of current adolescent treatment programs: 1) adolescent-specific treatment services; 2) the variety of therapeutic modalities; 3) relapse and recovery rates; and 4) the need for evidence-based, quality assessments and research. Current adolescent treatment efforts are summarized, and the recent literature regarding the efficacy of adolescent treatment and recovery rates is discussed. PMID:21701838

  17. New drugs and treatment targets in psoriasis.

    PubMed

    Kofoed, Kristian; Skov, Lone; Zachariae, Claus

    2015-02-01

    In recent years, the increased understanding of the pathophysiology of psoriasis has resulted in several new treatments. The success of ustekinumab proved the importance of the IL-23/T helper cell 17 axis in psoriatic diseases. Several new biologics targeting this axis will reach the clinic in the next years. Biologics are costly, require injections, and some patients experience tacaphylaxis, thus, the development of orally available, small-molecule inhibitors is desirable. Among small-molecules under investigation are A3 adenosine receptor agonists, Janus kinase inhibitors, and phosphodiesterase inhibitors. We review published clinical trials, and conference abstracts presented during the last years, concerned with new drugs under development for the treatment of psoriasis. In conclusion, our psoriasis armamentarium will be filled with several new effective therapeutic options the coming years. We need to be aware of the limitations of drug safety data when selecting new novel treatments. Monitoring and clinical registries are still important tools.

  18. Advances in the Treatment of Neuropathic Pain.

    PubMed

    Xu, Li; Zhang, Yuguan; Huang, Yuguang

    2016-01-01

    Neuropathic pain is pain that arises as a direct consequence of a lesion or diseases affecting the somatosensory system. Treatments for neuropathic pain include pharmacological, nonpharmacological, and interventional therapies. Currently recommended first-line pharmacological treatments include antidepressants and anticonvulsants (gabapentin and pregabalin). However, in some cases, pharmacological therapy alone fails to give adequate control of the chronic pain. New techniques have been invented and have been proved effective on neuropathic pain, such as behavioral, cognitive, integrative, and physical therapies. In this review, we focused on the advances in the treatment of central neuropathic pain, diabetic peripheral neuropathy, postherpetic neuralgia, and cancer pain. PMID:26900067

  19. FDA approved drugs as potential Ebola treatments

    PubMed Central

    Ekins, Sean; Coffee, Megan

    2015-01-01

    In the search for treatments for the Ebola Virus, multiple screens of FDA drugs have led to the identification of several with promising in vitro activity. These compounds were not originally developed as antivirals and some have been further tested in mouse in vivo models. We put forward the opinion that some of these drugs could be evaluated further and move into the clinic as they are already FDA approved and in many cases readily available. This may be important if there is a further outbreak in future and no other therapeutic is available. PMID:25789163

  20. Treatment of advanced non-small cell lung cancer.

    PubMed

    De Petris, L; Crinò, L; Scagliotti, G V; Gridelli, C; Galetta, D; Metro, G; Novello, S; Maione, P; Colucci, G; de Marinis, F

    2006-03-01

    In the last decade the treatment of advanced-metastatic non-small cell lung cancer has substantially improved. If in the early 90s there was still concern about the real efficacy of chemotherapy over best suppotive care alone in the advanced setting, constant developments in clinical research have demonstrated the survival advantage of active anti-cancer drugs not only in the first-line setting, but, lately, even in patients with recurrent disease after failure of two previous chemotherapy lines. With the premises of high throughput technologies, translational research is aiming to characterize patients and tumors on a molecular basis. With pharmacogenomics it would then be possible to accurately predict patient outcome and tailor the treatment strategy according to the geno-phenotype of single patients.

  1. Albumin-based nanocomposite spheres for advanced drug delivery systems.

    PubMed

    Misak, Heath E; Asmatulu, Ramazan; Gopu, Janani S; Man, Ka-Poh; Zacharias, Nora M; Wooley, Paul H; Yang, Shang-You

    2014-01-01

    A novel drug delivery system incorporating human serum albumin, poly(lactic-co-glycolic acid, magnetite nanoparticles, and therapeutic agent(s) was developed for potential application in the treatment of diseases such as rheumatoid arthritis and skin cancer. An oil-in-oil emulsion/solvent evaporation (O/OSE) method was modified to produce a drug delivery system with a diameter of 0.5–2 μm. The diameter was mainly controlled by adjusting the viscosity of albumin in the discontinuous phase of the O/OSE method. The drug-release study showed that the release of drug and albumin was mostly dependent on the albumin content of the drug delivery system, which is very similar to the drug occlusion-mesopore model. Cytotoxicity tests indicated that increasing the albumin content in the drug delivery system increased cell viability, possibly due to the improved biocompatibility of the system. Overall, these studies show that the proposed system could be a viable option as a drug delivery system in the treatment of many illnesses, such as rheumatoid arthritis, and skin and breast cancers. PMID:24106002

  2. Advances in nanomedicines for malaria treatment.

    PubMed

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

    2013-12-01

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

  3. Advances in nanomedicines for malaria treatment.

    PubMed

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

    2013-12-01

    Malaria is an infectious disease that mainly affects children and pregnant women from tropical countries. The mortality rate of people infected with malaria per year is enormous and became a public health concern. The main factor that has contributed to the success of malaria proliferation is the increased number of drug resistant parasites. To counteract this trend, research has been done in nanotechnology and nanomedicine, for the development of new biocompatible systems capable of incorporating drugs, lowering the resistance progress, contributing for diagnosis, control and treatment of malaria by target delivery. In this review, we discussed the main problems associated with the spread of malaria and the most recent developments in nanomedicine for anti-malarial drug delivery. PMID:24192063

  4. Current Pharmacological Advances in the Treatment of Cardiac Arrest

    PubMed Central

    Papastylianou, Andry; Mentzelopoulos, S.

    2012-01-01

    Cardiac arrest is defined as the sudden cessation of spontaneous ventilation and circulation. Within 15 seconds of cardiac arrest, the patient loses consciousness, electroencephalogram becomes flat after 30 seconds, pupils dilate fully after 60 seconds, and cerebral damage takes place within 90–300 seconds. It is essential to act immediately as irreversible damage can occur in a short time. Cardiopulmonary resuscitation (CPR) is an attempt to restore spontaneous circulation through a broad range of interventions which are early defibrillation, high-quality and uninterrupted chest compressions, advanced airway interventions, and pharmacological interventions. Drugs should be considered only after initial shocks have been delivered (when indicated) and chest compressions and ventilation have been started. During cardiopulmonary resuscitation, no specific drug therapy has been shown to improve survival to hospital discharge after cardiac arrest, and only few drugs have a proven benefit for short-term survival. This paper reviews current pharmacological treatment of cardiac arrest. There are three groups of drugs relevant to the management of cardiac arrest: vasopressors, antiarrhythmics, and other drugs such as sodium bicarbonate, calcium, magnesium, atropine, fibrinolytic drugs, and corticosteroids. PMID:22145080

  5. Adolescent drug addiction treatment and weight gain.

    PubMed

    Hodgkins, Candace C; Cahill, Kevin S; Seraphine, Anne E; Frost-Pineda, Kimberly; Gold, Mark S

    2004-01-01

    Neurotransmitter release in the nucleus accumbens use has been linked to self-administration and learning following drug use. This endogenous reward system is also activated following food intake or sex. Therefore, rebound hyperphagia following abstinence may be a mechanism to replenish the release of neurotransmitters in this reward system, leading to increased weight gain and a rise in body mass index during recovery from substance abuse. In this report, we examined the relationship between supervised drug abstinence and increased weight gain among adolescents at a residential substance abuse treatment center. Mean weight change over time was followed by repeated analysis of weight and body mass index. Significant weight gain and body mass index increase was observed during supervised and confirmed abstinence from drug use. Furthermore, significant interactions between tobacco use and primary substance use disorder with weight gain was demonstrated by multivariate analysis of variance.

  6. [Treatment strategy for advanced prostate cancer with bone metastases].

    PubMed

    Sugimoto, Mikio; Kakehi, Yoshiyuki

    2006-08-01

    The introduction of PSA screening has led to confirming a shift towards an earlier pathological stage in the diagnosis of prostate cancer. Consequently, the proportion of detecting early stage prostate cancer has clearly been increasing. On the other hand, progressive cancers in the form of distant metastases and locally advanced ones that have been confirmed at the initial diagnosis exhibit a constant rate. In addition, there have been a lot of cases where hormonal resistance was acquired during hormonal therapy which resulted in advanced metastases of the prostate. Prostate cancer has a tendency to be metastatic to bones. Combining the fact that the survival period of patients undergoing treatment is prolonged after metastases, the length of suffering caused by complications, such as ostealgia, pathological fracture and myelopathy, becomes an issue in which QOL and ADL of the patient are sacrificed for a long time. As for treatment of prostate cancer with metastases, a palliative treatment is common in the clinical scene. However, we can extend a life prognosis with use of radiotherapy and surgical treatment in addition to the palliative treatment at an appropriate time. It appears that a combination of new chemotherapy and hormonal therapy will be promising. In the future, we believe that the appearance of new anticancer drugs, endocrine therapies, bisphosphonates and strontium treatment could be used as a part of the treatment strategy for prostate cancer with bone metastases. PMID:16912523

  7. Recent advances in the construction of antibody-drug conjugates

    NASA Astrophysics Data System (ADS)

    Chudasama, Vijay; Maruani, Antoine; Caddick, Stephen

    2016-02-01

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

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

    PubMed

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

    2015-05-01

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

  9. [The treatment of atherosclerosis--drug therapy].

    PubMed

    Nakamura, H; Takahashi, Y

    1993-08-01

    Drug treatment against atherosclerosis has been evaluated recently in many epidemiological studies. Lipid Research Clinics Group convincingly reported in a large scale design that anion exchange resin effectively reduced blood cholesterol level and concomitantly decreased the events of coronary heart disease. Subsequently, anion exchange resin with or without combined administration of niacin or statin was found to inhibit the progression of coronary atherosclerotic lesions in FATS, SCOR, CLAS and STARS. Fenofibrate also successfully reduced the coronary artery narrowings. Based on these intervention studies, several hypocholesterolemic agents are definitely effective in the treatment of coronary atherosclerosis.

  10. The porphyrias: advances in diagnosis and treatment.

    PubMed

    Balwani, Manisha; Desnick, Robert J

    2012-11-29

    The inborn errors of heme biosynthesis, the porphyrias, are 8 genetically distinct metabolic disorders that can be classified as "acute hepatic," "hepatic cutaneous," and "erythropoietic cutaneous" diseases. Recent advances in understanding their pathogenesis and molecular genetic heterogeneity have led to improved diagnosis and treatment. These advances include DNA-based diagnoses for all the porphyrias, new understanding of the pathogenesis of the acute hepatic porphyrias, identification of the iron overload-induced inhibitor of hepatic uroporphyrin decarboxylase activity that causes the most common porphyria, porphyria cutanea tarda, the identification of an X-linked form of erythropoietic protoporphyria due to gain-of-function mutations in erythroid-specific 5-aminolevulinate synthase (ALAS2), and new and experimental treatments for the erythropoietic porphyrias. Knowledge of these advances is relevant for hematologists because they administer the hematin infusions to treat the acute attacks in patients with the acute hepatic porphyrias, perform the chronic phlebotomies to reduce the iron overload and clear the dermatologic lesions in porphyria cutanea tarda, and diagnose and treat the erythropoietic porphyrias, including chronic erythrocyte transfusions, bone marrow or hematopoietic stem cell transplants, and experimental pharmacologic chaperone and stem cell gene therapies for congenital erythropoietic protoporphyria. These developments are reviewed to update hematologists on the latest advances in these diverse disorders.

  11. The porphyrias: advances in diagnosis and treatment.

    PubMed

    Balwani, Manisha; Desnick, Robert J

    2012-01-01

    The inborn errors of heme biosynthesis, the porphyrias, are 8 genetically distinct metabolic disorders that can be classified as "acute hepatic," "hepatic cutaneous," and "erythropoietic cutaneous" diseases. Recent advances in understanding their pathogenesis and molecular genetic heterogeneity have led to improved diagnosis and treatment. These advances include DNA-based diagnoses for all the porphyrias, new understanding of the pathogenesis of the acute hepatic porphyrias, identification of the iron overload-induced inhibitor of hepatic uroporphyrin decarboxylase activity that causes the most common porphyria, porphyria cutanea tarda, the identification of an X-linked form of erythropoietic protoporphyria due to gain-of-function mutations in erythroid-specific 5-aminolevulinate synthase (ALAS2), and new and experimental treatments for the erythropoietic prophyrias. Knowledge of these advances is relevant for hematologists because they administer the hematin infusions to treat the acute attacks in patients with the acute hepatic porphyrias, perform the chronic phlebotomies to reduce the iron overload and clear the dermatologic lesions in porphyria cutanea tarda, and diagnose and treat the erythropoietic porphyrias, including chronic erythrocyte transfusions, bone marrow or hematopoietic stem cell transplants, and experimental pharmacologic chaperone and stem cell gene therapies for congenital erythropoietic protoporphyria. These developments are reviewed to update hematologists on the latest advances in these diverse disorders.

  12. Pharmacogenetics of alcohol, nicotine and drug addiction treatments.

    PubMed

    Sturgess, Jessica E; George, Tony P; Kennedy, James L; Heinz, Andreas; Müller, Daniel J

    2011-07-01

    The numerous premature deaths, medical complications and socio-economic repercussions of drug and alcohol addiction suggest that improvements in treatment strategies for addictive disorders are warranted. The use of pharmacogenetics to predict response to medication, side effects and appropriate dosages is relatively new in the field of drug addiction. However, increasing our understanding of the genetic factors influencing these processes may improve the treatment of addiction in the future. We examined the available scientific literature on pharmacogenetic advancements in the field of drug addiction with a focus on alcohol and tobacco to provide a summary of genes implicated in the effectiveness of pharmacotherapy for addiction. In addition, we reviewed pharmacogenetic research on cocaine and heroin dependence. Thus far, the most promising results were obtained for polymorphisms in the OPRM1 and CYP2A6 genes, which have been effective in predicting clinical response to naltrexone in alcoholism and nicotine replacement therapy in smoking, respectively. Opinions differ as to whether pharmacogenetic testing should be implemented in the clinic at this time because clinical utility and cost-effectiveness require further investigation. However, the data summarized in this review demonstrate that pharmacogenetic factors play a role in response to addiction pharmacotherapy and have the potential to aid in the personalization of addiction treatments. Such data may lead to improved cessation rates by allowing physicians to select medications for individuals based, at least in part, on genetic factors that predispose to treatment success or failure rather than on a trial and error basis. PMID:21362114

  13. Clinicians' perspectives on the use of drug-eluting contact lenses for the treatment of glaucoma.

    PubMed

    Taniguchi, Elise V; Kalout, Patricia; Pasquale, Louis R; Kohane, Daniel S; Ciolino, Joseph B

    2014-10-01

    Glaucoma is the leading cause of irreversible blindness worldwide. The perspective of clinicians who treat the disease is important and may ultimately dictate the adoption of new treatment modalities, such as drug-eluting contact lenses. Recent advances have enabled contact lenses to serve as a sustained-release drug-delivery platform capable of treating glaucoma. This review covers the medical treatment of glaucoma, suboptimal adherence rates to treatment, and factors that may influence the clinical applicability of drug-eluting contact lenses. Ophthalmologists who treat glaucoma were surveyed to determine their perspective on treatment adherence, bandage contact lens use and the use of a drug-eluting contact lens to treat glaucoma. Given the challenge of treating glaucoma and the clinical need for improved drug delivery, drug-eluting contact lenses appear to be a promising treatment option.

  14. Food and Drug Administration process for development and approval of drugs and radiopharmaceuticals: treatments in urologic oncology.

    PubMed

    Ning, Yang-Min; Maher, V Ellen

    2015-03-01

    Regulatory advice and assessment play an important role in the successful development of new drugs and radiopharmaceuticals for the treatment of urologic malignancies. Cooperation between the US Food and Drug Administration (FDA) and the pharmaceutical industry has led to the approval of more than 20 new urologic oncology products in the last 2 decades. Despite these advances, more effective treatments need to be developed and approved for the treatment of urologic malignancies. This review provides general information about the FDA's role in the development of investigational new drugs, with an emphasis on the regulatory process and the requirements for marketing approval. In addition, this review summarizes the products for the treatment of urologic malignancies that were approved by the FDA in the last 30 years and the key issues concerning urologic oncology products that were discussed publicly at Oncologic Drug Advisory Committee meetings in the past 10 years.

  15. Personalizing Drug Selection Using Advanced Clinical Decision Support

    PubMed Central

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

    2009-01-01

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

  16. Drug Users' Views of Psychosocial Aspects of their Treatment Environment.

    ERIC Educational Resources Information Center

    Penk, W. E.; Robinowitz, R.

    1978-01-01

    Multiple discriminant function analysis indicates that drug users see and want a treatment environment that allows open expression of feeling (spontaneity) and control (staff control). These apparently contradictory environmental dimensions define the dilemma in drug treatment, i.e., how to control drug use and simultaneously cope with drug users'…

  17. Advances and Challenges of Liposome Assisted Drug Delivery

    PubMed Central

    Sercombe, Lisa; Veerati, Tejaswi; Moheimani, Fatemeh; Wu, Sherry Y.; Sood, Anil K.; Hua, Susan

    2015-01-01

    The application of liposomes to assist drug delivery has already had a major impact on many biomedical areas. They have been shown to be beneficial for stabilizing therapeutic compounds, overcoming obstacles to cellular and tissue uptake, and improving biodistribution of compounds to target sites in vivo. This enables effective delivery of encapsulated compounds to target sites while minimizing systemic toxicity. Liposomes present as an attractive delivery system due to their flexible physicochemical and biophysical properties, which allow easy manipulation to address different delivery considerations. Despite considerable research in the last 50 years and the plethora of positive results in preclinical studies, the clinical translation of liposome assisted drug delivery platforms has progressed incrementally. In this review, we will discuss the advances in liposome assisted drug delivery, biological challenges that still remain, and current clinical and experimental use of liposomes for biomedical applications. The translational obstacles of liposomal technology will also be presented. PMID:26648870

  18. Drug Discovery and Development of Antimalarial Agents: Recent Advances.

    PubMed

    Thota, Sreekanth; Yerra, Rajeshwar

    2016-01-01

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

  19. Recent advances in immunosensor for narcotic drug detection

    PubMed Central

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

    2015-01-01

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

  20. New advances in targeted gastric cancer treatment.

    PubMed

    Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

    2016-08-14

    Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours. PMID:27570417

  1. New advances in targeted gastric cancer treatment

    PubMed Central

    Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

    2016-01-01

    Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours. PMID:27570417

  2. [Drug Treatment of Chronic Venous Diesease].

    PubMed

    Pavlović, Miloš D

    2016-06-01

    Chronic venous disease (CVD) affects at least 15-25 % of the general population incurring not only high morbidity but also considerable economical burden. The mainstay of modern treatment of CVD are endovenous therapeutic procedures and compression therapy. As far as the pathogenesis of CVD is being gradually unraveled the interest in drugs able to impact the process is growing. Here we have presented an overview of a majority of oral preparations used so far to treat CVD including venous leg ulcers. After several decades of clinical use a few flavonoid preparations, in the first place micronized purified flavonoid fraction, collected enough evidence to recommend them as a short-term adjunct treatment of CVD. However, other compounds are also promising in this regards. Yet, we need more larger and longer-term clinical trials to more precisely define effects, cost-effectiveness and, above all, capacity for prophylactic application of the drugs. Learning more about basis of CVD will help design new drugs directed at specific aspects of the disease process. PMID:27379855

  3. Applying laboratory research: drug anticipation and the treatment of drug addiction.

    PubMed

    Siegel, Shepard; Ramos, Barbara M C

    2002-08-01

    Basic research concerning drug tolerance and withdrawal may inform clinical practice, and vice versa. Three areas that integrate the work of the laboratory and the clinic are discussed: (a) drug overdose, (b) cue exposure treatment of addiction, and (c) pharmacological treatment of withdrawal symptoms. The areas are related in that they indicate the contribution of drug-paired cues to the effects of addictive drugs and the role of Pavlovian conditioning of drug effects in drug tolerance and withdrawal symptoms.

  4. Treatment of diabetic retinopathy: Recent advances and unresolved challenges

    PubMed Central

    Stewart, Michael W

    2016-01-01

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

  5. Treatment of diabetic retinopathy: Recent advances and unresolved challenges.

    PubMed

    Stewart, Michael W

    2016-08-25

    Diabetic retinopathy (DR) is the leading cause of blindness in industrialized countries. Remarkable advances in the diagnosis and treatment of DR have been made during the past 30 years, but several important management questions and treatment deficiencies remain unanswered. The global diabetes epidemic threatens to overwhelm resources and increase the incidence of blindness, necessitating the development of innovative programs to diagnose and treat patients. The introduction and rapid adoption of intravitreal pharmacologic agents, particularly drugs that block the actions of vascular endothelial growth factor (VEGF) and corticosteroids, have changed the goal of DR treatment from stabilization of vision to improvement. Anti-VEGF injections improve visual acuity in patients with diabetic macular edema (DME) from 8-12 letters and improvements with corticosteroids are only slightly less. Unfortunately, a third of patients have an incomplete response to anti-VEGF therapy, but the best second-line therapy remains unknown. Current first-line therapy requires monthly visits and injections; longer acting therapies are needed to free up healthcare resources and improve patient compliance. VEGF suppression may be as effective as panretinal photocoagulation (PRP) for proliferative diabetic retinopathy, but more studies are needed before PRP is abandoned. For over 30 years laser was the mainstay for the treatment of DME, but recent studies question its role in the pharmacologic era. Aggressive treatment improves vision in most patients, but many still do not achieve reading and driving vision. New drugs are needed to add to gains achieved with available therapies. PMID:27625747

  6. Recent advances and novel treatment paradigms in acute lymphocytic leukemia

    PubMed Central

    Papadantonakis, Nikolaos; Advani, Anjali S.

    2016-01-01

    This is an exciting time in the treatment of acute lymphoblastic leukemia (ALL) given the advances in the relapsed/refractory setting. The development of antibody treatments (including antibody drug conjugates with toxins) offers a different treatment approach compared with conventional chemotherapy regimens. Moreover, the use of bispecific T-cell-engager antibodies (BiTEs) such as blinatumomab harness the cytotoxic activity of T cells against CD19-positive lymphoblasts. Another strategy involves the use of chimeric antigen receptor (CAR) T cells. CAR T cells have demonstrated promising results in the relapsed/refractory setting. However, the use of BiTEs and CAR T cells is also associated with a distinct set of adverse reactions that must be taken into account by the treating physician. Apart from the above strategies, the use of other targeted therapies has attracted interest. Namely, the discovery of the Philadelphia (Ph)-like signature in children and young adults with ALL has led to the use of tyrosine kinase inhibitors (TKI) in these patients. The different drugs and strategies that are being tested in the relapsed/refractory ALL setting pose a unique challenge in identifying the optimum sequence of treatment and determining which approaches should be considered for frontline treatment.

  7. Treatment of diabetic retinopathy: Recent advances and unresolved challenges

    PubMed Central

    Stewart, Michael W

    2016-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness in industrialized countries. Remarkable advances in the diagnosis and treatment of DR have been made during the past 30 years, but several important management questions and treatment deficiencies remain unanswered. The global diabetes epidemic threatens to overwhelm resources and increase the incidence of blindness, necessitating the development of innovative programs to diagnose and treat patients. The introduction and rapid adoption of intravitreal pharmacologic agents, particularly drugs that block the actions of vascular endothelial growth factor (VEGF) and corticosteroids, have changed the goal of DR treatment from stabilization of vision to improvement. Anti-VEGF injections improve visual acuity in patients with diabetic macular edema (DME) from 8-12 letters and improvements with corticosteroids are only slightly less. Unfortunately, a third of patients have an incomplete response to anti-VEGF therapy, but the best second-line therapy remains unknown. Current first-line therapy requires monthly visits and injections; longer acting therapies are needed to free up healthcare resources and improve patient compliance. VEGF suppression may be as effective as panretinal photocoagulation (PRP) for proliferative diabetic retinopathy, but more studies are needed before PRP is abandoned. For over 30 years laser was the mainstay for the treatment of DME, but recent studies question its role in the pharmacologic era. Aggressive treatment improves vision in most patients, but many still do not achieve reading and driving vision. New drugs are needed to add to gains achieved with available therapies. PMID:27625747

  8. Carrier-Based Drug Delivery System for Treatment of Acne

    PubMed Central

    Vyas, Amber; Kumar Sonker, Avinesh

    2014-01-01

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

  9. Sex differences in drug abuse: Etiology, prevention, and treatment.

    PubMed

    Evans, Suzette M; Reynolds, Brady

    2015-08-01

    This special issue exemplifies one of the major goals of the current editor of Experimental and Clinical Psychopharmacology (Dr. Suzette Evans): to increase the number of manuscripts that emphasize females and address sex differences. Taken together, these articles represent a broad range of drug classes and approaches spanning preclinical research to treatment to better understand the role of sex differences in drug abuse. While not all studies found sex differences, we want to emphasize that finding no sex difference is just as important as confirming one, and should be reported in peer-reviewed journals. It is our intention and hope that this special issue will further advance scientific awareness about the importance of accounting for sex differences in the study of substance abuse. Participant sex is an essential variable to consider in developing a more comprehensive understanding of substance abuse. Rather than viewing investigating sex differences as burdensome, investigators should seize this opportune area ripe for innovative research that is long overdue.

  10. Recent advances in Essential Tremor: Surgical treatment.

    PubMed

    Picillo, Marina; Fasano, Alfonso

    2016-01-01

    While no real breakthrough in the medical treatment of Essential Tremor (ET) has recently emerged, surgical field is expanding exponentially. Purpose of this review is to examine the recent and future developments of the surgical treatments for ET. Technological advances are shaping the present and the future application of deep brain stimulation (DBS) in ET. New electrode configurations as well as new implantable pulse generators are now available. Application of closed-loop or adaptive stimulation in clinical practice will allow DBS to deliver stimulation in a truly physiological way to restore aberrant neurological circuits on demand, thus avoiding side effects, tolerance and also saving the battery life. Besides DBS and standard thalamotomy, novel surgical approaches for ET are on the horizon. The development of MRI-guided focused ultrasound technique has been the new frontier of deep brain lesional therapies. Although the benefit of motor cortex stimulation is yet to be defined, this minimally invasive approach remains intriguing. Although the advances of surgical treatments along the clinical and technological directions described in this review will certainly contribute to a successful management of ET patients, future studies need to consider critical issues such as the heterogeneity of ET and the development of tolerance. PMID:26382842

  11. Recent advances in Essential Tremor: Surgical treatment.

    PubMed

    Picillo, Marina; Fasano, Alfonso

    2016-01-01

    While no real breakthrough in the medical treatment of Essential Tremor (ET) has recently emerged, surgical field is expanding exponentially. Purpose of this review is to examine the recent and future developments of the surgical treatments for ET. Technological advances are shaping the present and the future application of deep brain stimulation (DBS) in ET. New electrode configurations as well as new implantable pulse generators are now available. Application of closed-loop or adaptive stimulation in clinical practice will allow DBS to deliver stimulation in a truly physiological way to restore aberrant neurological circuits on demand, thus avoiding side effects, tolerance and also saving the battery life. Besides DBS and standard thalamotomy, novel surgical approaches for ET are on the horizon. The development of MRI-guided focused ultrasound technique has been the new frontier of deep brain lesional therapies. Although the benefit of motor cortex stimulation is yet to be defined, this minimally invasive approach remains intriguing. Although the advances of surgical treatments along the clinical and technological directions described in this review will certainly contribute to a successful management of ET patients, future studies need to consider critical issues such as the heterogeneity of ET and the development of tolerance.

  12. [Female sexual dysfunction: Drug treatment options].

    PubMed

    Alcántara Montero, A; Sánchez Carnerero, C I

    2016-01-01

    Many women will likely experience a sexual problem in their lifetime. Female sexual dysfunction is a broad term used to describe 3 categories of disorders of a multifactorial nature. Effective, but limited pharmacotherapeutic options exist to address female sexual dysfunction. The FDA recently approved the first agent for treatment of hypoactive sexual desire disorder in pre-menopausal women. Off-label use of hormonal therapies, particularly oestrogen and testosterone, are the most widely employed for female sexual dysfunction, particularly in post-menopausal women. Other drugs currently under investigation include phosphodiesterase inhibitors and agents that modulate dopamine or melanocortin receptors. PMID:27041639

  13. Emerging Drugs for the Treatment of Anxiety

    PubMed Central

    Murrough, James W.; Yaqubi, Sahab; Sayed, Sehrish; Charney, Dennis S.

    2016-01-01

    Introduction Anxiety disorders are among the most prevalent and disabling psychiatric disorders in the United States and worldwide. Basic research has provided critical insights into the mechanism regulating fear behavior in animals and a host of animal models have been developed in order to screen compounds for anxiolytic properties. Despite this progress, no mechanistically novel agents for the treatment of anxiety have come to market in more than two decades. Areas covered The current review will provide a critical summary of current pharmacological approaches to the treatment of anxiety and will examine the pharmacotherapeutic pipeline for treatments in development. Anxiety and related disorders considered herein include panic disorder, social anxiety disorder, generalized anxiety disorder and posttraumatic stress disorder. The glutamate, neuropeptide and endocannabinoid systems show particular promise as future targets for novel drug development. Expert opinion In the face of an ever-growing understanding of fear related behavior, the field awaits the translation of this research into mechanistically novel treatments. Obstacles will be overcome through close collaboration between basic and clinical researchers with the goal of aligning valid endophenotypes of human anxiety disorders with improved animal models. Novel approaches are needed to move basic discoveries into new, more effective treatments for our patients. PMID:26012843

  14. Prevention and treatment of drug-induced liver disease.

    PubMed

    Speeg, K V; Bay, M K

    1995-12-01

    Many drugs may cause liver damage; some damage is predictable, but most is not. The most important preventive measure is judicious drug use by the prescribing physician. Early recognition of hepatotoxicity and cessation of the offending agent is essential for treatment. The best example of a specific treatment for drug-induced liver disease is N-acetylcysteine treatment for acetaminophen hepatotoxicity. Many examples are cited of other attempts at treatment in animal models of drug-induced liver disease. If drug-induced liver disease leads to fulminant hepatic failure, intensive management of the resulting complications is required. Liver transplantation may be the only treatment option.

  15. Drug treatment clients' readiness for hepatitis C treatment: implications for expanding treatment services in drug and alcohol settings.

    PubMed

    Treloar, Carla; Holt, Martin

    2008-08-01

    This study explores the perception of and readiness for hepatitis C treatment within a sample of 77 clients already participating in drug treatment, with a view to identifying likely barriers and incentives to hepatitis C treatment within a drug treatment population. Participants with hepatitis C did not demonstrate a consistent, indepth knowledge of the infection, lacked confidence in symptom recognition, and had little awareness of treatment options. Those without obvious symptoms or liver deterioration did not have a pressing interest in treatment, and many had heard concerning stories about the side effects of hepatitis C treatment. For those coping with anxiety or depression, the increased risk of a depressive episode under interferon treatment was a major barrier to treatment. PMID:18666886

  16. Recent advances in treatment of aplastic anemia

    PubMed Central

    Shin, Seung Hwan; Lee, Sung Eun

    2014-01-01

    Recent advances in the treatment of aplastic anemia (AA) made most of patients to expect to achieve a long-term survival. Allogeneic stem cell transplantation (SCT) from HLA-matched sibling donor (MSD-SCT) is a preferred first-line treatment option for younger patients with severe or very severe AA, whereas immunosuppressive treatment (IST) is an alternative option for others. Horse anti-thymocyte globuline (ATG) with cyclosporin A (CsA) had been a standard IST regimen with acceptable response rate. Recently, horse ATG had been not available and replaced with rabbit ATG in most countries. Subsequently, recent comparative studies showed that the outcomes of patients who received rabbit ATG/CsA were similar or inferior compared to those who received horse ATG/CsA. Therefore, further studies to improve the outcomes of IST, including additional eltrombopag, are necessary. On the other hand, the upper age limit of patients who are able to receive MSD-SCT as first-line treatment is a current issue because of favorable outcomes of MSD-SCT of older patients using fludarabine-based conditioning. In addition, further studies to improve the outcomes of patients who receive allogeneic SCT from alternative donors are needed. In this review, current issues and the newly emerging trends that may improve their outcomes in near futures will be discussed focusing the management of patients with AA. PMID:25378968

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

    PubMed

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

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment. PMID:27517036

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

    PubMed Central

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

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment. PMID:27517036

  19. In vivo brain microdialysis: advances in neuropsychopharmacology and drug discovery

    PubMed Central

    Darvesh, Altaf S.; Carroll, Richard T.; Geldenhuys, Werner J.; Gudelsky, Gary A.; Klein, Jochen; Meshul, Charles K.; Van der Schyf, Cornelis J.

    2010-01-01

    Introduction Microdialysis is an important in vivo sampling technique, useful in the assay of extracellular tissue fluid. The technique has both pre-clinical and clinical applications but is most widely used in neuroscience. The in vivo microdialysis technique allows measurement of neurotransmitters such as acetycholine (ACh), the biogenic amines including dopamine (DA), norepinephrine (NE) and serotonin (5-HT), amino acids such as glutamate (Glu) and gamma aminobutyric acid (GABA), as well as the metabolites of the aforementioned neurotransmitters, and neuropeptides in neuronal extracellular fluid in discrete brain regions of laboratory animals such as rodents and non-human primates. Areas covered In this review we present a brief overview of the principles and procedures related to in vivo microdialysis and detail the use of this technique in the pre-clinical measurement of drugs designed to be used in the treatment of chemical addiction, neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and as well as psychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD) and schizophrenia. This review offers insight into the tremendous utility and versatility of this technique in pursuing neuropharmacological investigations as well its significant potential in rational drug discovery. Expert opinion In vivo microdialysis is an extremely versatile technique, routinely used in the neuropharmacological investigation of drugs used for the treatment of neurological disorders. This technique has been a boon in the elucidation of the neurochemical profile and mechanism of action of several classes of drugs especially their effects on neurotransmitter systems. The exploitation and development of this technique for drug discovery in the near future will enable investigational new drug candidates to be rapidly moved into the clinical trial stages and to market thus providing new successful therapies for neurological diseases

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

    ERIC Educational Resources Information Center

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

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

  1. Treatment Retention and Changes in Motivation among Drug Court Probationers

    ERIC Educational Resources Information Center

    Kinlock, Timothy W.; Sears, Emily A.; O'Grady, Kevin E.; Callaman, Jason M.; Brown, Barry S.

    2009-01-01

    This study examined whether Motivational Interviewing (MI), found effective with voluntary entrants to drug treatment, would improve intrinsic motivation and treatment retention among drug court probationers. Probationers were randomly assigned to receive either a two-session MI intervention or a two-session Drug Education (DE) intervention…

  2. Systematic review of the impact of adult drug treatment courts

    PubMed Central

    Brown, Randall T.

    2010-01-01

    The U.S. correctional system is overburdened by individuals suffering from substance use disorders. These illnesses also exact a heavy toll in individual and public health and well-being. Effective methods for reducing the negative impact of substance use disorders comprise critical concerns for policy makers. Drug court treatment programs (DTCs) are present in over 1800 county, tribal, and territorial jurisdictions in the United States, as an alternative to incarceration for offenders with substance use disorders. This review article summarizes available descriptive information on representative drug treatment court populations, summarizes observational studies of drug court participants, and specifically reviews available experimental effectiveness literature on drug treatment courts. The review concludes by examining limitations of the current literature, challenges to conducting research in drug court samples, and potential future directions for research on drug treatment court interventions. Review of non-experimental and quasi-experimental literature regarding the impact of drug treatment courts point toward benefit vs. traditional adjudication in averting future criminal behavior and in reducing future substance use, at least in the short term. Randomized effectiveness studies of drug treatment courts are scant (three identified in the literature on U.S. adult drug courts), and methodological issues arise in combining their findings. These randomized trials failed to demonstrate consistent effect upon re-arrest rates for drug-involved offenders participating in drug treatment court vs. typical adjudication. The two studies examining reconviction and reincarceration, however, demonstrated reductions for the drug treatment court group vs. those typically adjudicated. PMID:20478542

  3. A Qualitative Exploration of Drug Abuse Relapse Following Treatment

    ERIC Educational Resources Information Center

    Islam, Manirul; Hashizume, Masahiro; Yamamoto, Taro; Alam, Faruq; Rabbani, Golam

    2012-01-01

    Drug use is an alarming issue in Bangladesh. Most drug users return to drugs after treatment, in what becomes a vicious cycle of treatment and relapse. This study explored why they return and what pathways they follow. We carried out 5 key informant interviews, 10 in-depth interviews, 2 focus group discussions, 3 case studies, 8 observations, and…

  4. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells.

    PubMed

    Kawser Hossain, Mohammed; Abdal Dayem, Ahmed; Han, Jihae; Kumar Saha, Subbroto; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2016-01-01

    Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies. PMID:26907255

  5. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells

    PubMed Central

    Kawser Hossain, Mohammed; Abdal Dayem, Ahmed; Han, Jihae; Kumar Saha, Subbroto; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2016-01-01

    Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies. PMID:26907255

  6. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells.

    PubMed

    Kawser Hossain, Mohammed; Abdal Dayem, Ahmed; Han, Jihae; Kumar Saha, Subbroto; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2016-01-01

    Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies.

  7. Advances in systemic treatment for nasopharyngeal carcinoma.

    PubMed

    Tan, Wan-Ling; Tan, Eng-Huat; Lim, Darren Wan-Teck; Ng, Quan-Sing; Tan, Daniel Shao-Weng; Jain, Amit; Ang, Mei-Kim

    2016-04-01

    Nasopharyngeal carcinoma (NPC) is a unique disease endemic in Asia. It is etiologically linked to the Epstein-Barr virus and is both radio- and chemo-sensitive. While radiotherapy (RT) remains the primary treatment modality with high cure rates for early stage disease, systemic treatment forms an important integral component in the treatment of NPC, both in the non-metastatic as well as palliative setting. Presently, standard therapy in locally advanced NPC comprises conventional cytotoxic chemotherapy administered concurrently during RT. The role of induction chemotherapy and adjuvant chemotherapy remain to be well-defined. Further research strategies in non-metastatic disease will require better identification of patients with high risk disease, and determining the optimal sequence and combination of chemotherapeutic regimens. In metastatic disease, whilst chemotherapy remains the mainstay of care, resistance inevitably develops. Development of molecularly targeted therapies has not yielded much success to date, and further research has been focused on development of EBV-targeted strategies such as vaccination or administration of cytotoxic T-cells directed towards EBV, as well as evaluation of immune checkpoint inhibition approaches. PMID:27121881

  8. Biogenic metals in advanced water treatment.

    PubMed

    Hennebel, Tom; De Gusseme, Bart; Boon, Nico; Verstraete, Willy

    2009-02-01

    Microorganisms can change the oxidation state of metals and concomitantly deposit metal oxides and zerovalent metals on or into their cells. The microbial mechanisms involved in these processes have been extensively studied in natural environments, and researchers have recently gained interest in the applications of microbe-metal interactions in biotechnology. Because of their specific characteristics, such as high specific surface areas and high catalytic reactivity, biogenic metals offer promising perspectives for the sorption and (bio)degradation of contaminants. In this review, the precipitation of biogenic manganese and iron species and the microbial reduction of precious metals, such as palladium, platinum, silver and gold, are discussed with specific attention to the application of these biogenic metals in innovative remediation technologies in advanced water treatment.

  9. Bell's Palsy: Treatment with Steroids and Antiviral Drugs

    MedlinePlus

    ... PATIENTS and their FAMILIES BELL’S PALSY: TREATMENT WITH STEROIDS AND ANTIVIRAL DRUGS This information sheet is provided to help you understand the role of steroids and antiviral drugs for treating Bell’s palsy. Neurologists ...

  10. 24 CFR 960.205 - Drug use by applicants: Obtaining information from drug treatment facility.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... required by 42 CFR 2.31; and (iii) Authorizes the PHA to receive such information from the drug abuse.... This section addresses a PHA's authority to request and obtain information from drug abuse treatment... household member. (2) Drug abuse treatment facility. An entity: (i) That holds itself out as providing,...

  11. 24 CFR 960.205 - Drug use by applicants: Obtaining information from drug treatment facility.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... required by 42 CFR 2.31; and (iii) Authorizes the PHA to receive such information from the drug abuse.... This section addresses a PHA's authority to request and obtain information from drug abuse treatment... household member. (2) Drug abuse treatment facility. An entity: (i) That holds itself out as providing,...

  12. 24 CFR 960.205 - Drug use by applicants: Obtaining information from drug treatment facility.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... required by 42 CFR 2.31; and (iii) Authorizes the PHA to receive such information from the drug abuse.... This section addresses a PHA's authority to request and obtain information from drug abuse treatment... household member. (2) Drug abuse treatment facility. An entity: (i) That holds itself out as providing,...

  13. Advanced Cell Culture Techniques for Cancer Drug Discovery

    PubMed Central

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

    2014-01-01

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

  14. Current therapies and technological advances in aqueous aerosol drug delivery.

    PubMed

    Watts, Alan B; McConville, Jason T; Williams, Robert O

    2008-09-01

    Recent advances in aerosolization technology have led to renewed interest in pulmonary delivery of a variety of drugs. Pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) have experienced success in recent years; however, many limitations are presented by formulation difficulties, inefficient delivery, and complex device designs. Simplification of the formulation process as well as adaptability of new devices has led many in the pharmaceutical industry to reconsider aerosolization in an aqueous carrier. In the acute care setting, breath-enhanced air-jet nebulizers are controlling and minimizing the amount of wasted medication, while producing a high percentage of respirable droplets. Vibrating mesh nebulizers offer advantages in higher respirable fractions (RFs) and slower velocity aerosols when compared with air-jet nebulizers. Vibrating mesh nebulizers incorporating formulation and patient adaptive components provide improvements to continuous nebulization technology by generating aerosol only when it is most likely to reach the deep lung. Novel innovations in generation of liquid aerosols are now being adapted for propellant-free pulmonary drug delivery to achieve unprecedented control over dose delivered and are leading the way for the adaptation of systemic drugs for delivery via the pulmonary route. Devices designed for the metered dose delivery of insulin, morphine, sildenafil, triptans, and various peptides are all currently under investigation for pulmonary delivery to treat nonrespiratory diseases. Although these devices are currently still in clinical testing (with the exception of the Respimat), metered dose liquid inhalers (MDLIs) have already shown superior outcomes to current pulmonary and systemic delivery methods.

  15. Recent advances in lymphatic targeted drug delivery system for tumor metastasis

    PubMed Central

    Zhang, Xiao-Yu; Lu, Wei-Yue

    2014-01-01

    The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers. PMID:25610710

  16. Advances in drug delivery via electrospun and electrosprayed nanomaterials.

    PubMed

    Zamani, Maedeh; Prabhakaran, Molamma P; Ramakrishna, Seeram

    2013-01-01

    Electrohydrodynamic (EHD) techniques refer to procedures that utilize electrostatic forces to fabricate fibers or particles of different shapes with sizes in the nano-range to a few microns through electrically charged fluid jet. Employing different techniques, such as blending, surface modification, and coaxial process, there is a great possibility of incorporating bioactive such molecules as drugs, DNA, and growth factors into the nanostructures fabricated via EHD techniques. By careful selection of materials and processing conditions, desired encapsulation efficiency as well as preserved bioactivity of the therapeutic agents can be achieved. The drug-loaded nanostructures produced can be applied via different routes, such as implantation, injection, and topical or oral administration for a wide range of disease treatment. Taking advantage of the recent developments in EHD techniques like the coaxial process or multilayered structures, individually controlled delivery of multiple drugs is achievable, which is of great demand in cancer therapy and growth-factor delivery. This review summarizes the most recent techniques and postmodification methods to fabricate electrospun nanofibers and electrosprayed particles for drug-delivery applications.

  17. Advances in drug delivery via electrospun and electrosprayed nanomaterials

    PubMed Central

    Zamani, Maedeh; Prabhakaran, Molamma P; Ramakrishna, Seeram

    2013-01-01

    Electrohydrodynamic (EHD) techniques refer to procedures that utilize electrostatic forces to fabricate fibers or particles of different shapes with sizes in the nano-range to a few microns through electrically charged fluid jet. Employing different techniques, such as blending, surface modification, and coaxial process, there is a great possibility of incorporating bioactive such molecules as drugs, DNA, and growth factors into the nanostructures fabricated via EHD techniques. By careful selection of materials and processing conditions, desired encapsulation efficiency as well as preserved bioactivity of the therapeutic agents can be achieved. The drug-loaded nanostructures produced can be applied via different routes, such as implantation, injection, and topical or oral administration for a wide range of disease treatment. Taking advantage of the recent developments in EHD techniques like the coaxial process or multilayered structures, individually controlled delivery of multiple drugs is achievable, which is of great demand in cancer therapy and growth-factor delivery. This review summarizes the most recent techniques and postmodification methods to fabricate electrospun nanofibers and electrosprayed particles for drug-delivery applications. PMID:23976851

  18. Advances in Drug Delivery to the Posterior Segment

    PubMed Central

    Pearce, William; Hsu, Jason; Yeh, Steven

    2015-01-01

    Purpose Emerging developments and research for drug delivery to the posterior segment offer a promising future for the treatment of vitreoretinal disease. As new technologies enter the market, clinicians should be aware of new indications and ongoing clinical trials. Recent Findings This review summarizes the advantages and shortcomings of the most commonly used drug delivery methods including vitreous dynamics, physician sustainability and patient preferences. Currently available intravitreal corticosteroid-release devices offer surgical and in-office management of retinal vascular disease and posterior uveitis. The suprachoroidal space offers a new anatomic location for the delivery of lower dose medications directly to the target tissue. Implantable drug reservoirs would potentially allow for less frequent intravitreal injections reducing treatment burdens and associated risks. Newer innovations in encapsulated cell technology offer promising results in early clinical trials. Summary While pars plana intravitreal injection remains the mainstay of therapy for many vitreoretinal diseases, targeted delivery and implantable eluting devices are rapidly demonstrating safety and efficacy. These therapeutic modalities offer promising options for the vitreoretinal therapeutic landscape. PMID:25759965

  19. Advances in diagnosis and treatment of trigeminal neuralgia.

    PubMed

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

    2015-01-01

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

  20. Advances in diagnosis and treatment of trigeminal neuralgia

    PubMed Central

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

    2015-01-01

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

  1. Advances in non-dopaminergic treatments for Parkinson's disease

    PubMed Central

    Stayte, Sandy; Vissel, Bryce

    2014-01-01

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

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

    PubMed

    Carroll, Marilyn E; Smethells, John R

    2015-01-01

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

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

    PubMed Central

    Carroll, Marilyn E.; Smethells, John R.

    2016-01-01

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

  4. Recent advances in computer-aided drug design as applied to anti-influenza drug discovery.

    PubMed

    Mallipeddi, Prema L; Kumar, Gyanendra; White, Stephen W; Webb, Thomas R

    2014-01-01

    Influenza is a seasonal and serious health threat, and the recent outbreak of H7N9 following the pandemic spread of H1N1 in 2009 has served to emphasize the importance of anti-influenza drug discovery. Zanamivir (Relenza™) and oseltamivir (Tamiflu(®)) are two antiviral drugs currently recommended by the CDC for treating influenza. Both are examples of the successful application of structure-based drug design strategies. These strategies have combined computer- based approaches, such as docking- and pharmacophore-based virtual screening with X-ray crystallographic structural analyses. Docking is a routinely used computational method to identify potential hits from large compound libraries. This method has evolved from simple rigid docking approaches to flexible docking methods to handle receptor flexibility and to enhance hit rates in virtual screening. Virtual screening approaches can employ both ligand-based and structurebased pharmacophore models depending on the available information. The exponential growth in computing power has increasingly facilitated the application of computer-aided methods in drug discovery, and they now play significant roles in the search for novel therapeutics. An overview of these computational tools is presented in this review, and recent advances and challenges will be discussed. The focus of the review will be anti-influenza drug discovery and how advances in our understanding of viral biology have led to the discovery of novel influenza protein targets. Also discussed will be strategies to circumvent the problem of resistance emerging from rapid mutations that has seriously compromised the efficacy of current anti-influenza therapies.

  5. Advances in the diagnosis, pathogenesis and treatment of CIDP.

    PubMed

    Dalakas, Marinos C

    2011-08-16

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common chronic autoimmune neuropathy. Despite clinical challenges in diagnosis-owing in part to the existence of disease variants, and different views on how many electrophysiological abnormalities are needed to document demyelination-consensus criteria seem to have been reached for research or clinical practice. Current standard of care involves corticosteroids, intravenous immunoglobulin (IVIg) and/or plasmapheresis, which provide short-term benefits. Maintenance therapy with IVIg can induce sustained remission, increase quality of life and prevent further axonal loss, but caution is needed to avoid overtreatment. Commonly used immunosuppressive drugs offer minimal benefit, necessitating the development of new therapies for treatment-refractory patients. Advances in our understanding of the underlying immunopathology in CIDP have identified new targets for future therapeutic efforts, including T cells, B cells, and transmigration and transduction molecules. New biomarkers and scoring systems represent emerging tools with the potential to predict therapeutic responses and identify patients with active disease for enrollment into clinical trials. This Review highlights the recent advances in diagnosing CIDP, provides an update on the immunopathology including new target antigens, and discusses current treatments, ongoing challenges and future therapeutic directions.

  6. Oral Antifungal Drugs in the Treatment of Dermatomycosis.

    PubMed

    Tsunemi, Yuichiro

    2016-01-01

    Oral antifungal drugs are used primarily to treat tinea unguium; however, they are also useful for other types of tinea. For example, a combination of topical and oral antifungal drugs is effective in hyperkeratotic tinea pedis that is unresponsive to topical monotherapy. In cases of tinea facialis adjacent to the eyes, ears, or mouth, or widespread tinea corporis, or tinea cruris involving the complex skin folds of the external genitalia, it is difficult to apply topical drugs to all the lesions; therefore, oral antifungal drugs are necessary. Oral antifungal drugs are also useful not only for tinea but for widespread pityriasis versicolor and Malassezia folliculitis, candidal onychomycosis, and candidal paronychia and onychia. Topical antifungal drugs are in fact unsuitable for some mycoses. In tinea capitis, for example, irritation by topical drugs is likely to enhance inflammation; therefore, oral antifungal drug monotherapy is preferable. In interdigital tinea pedis with erosion or contact dermatitis, topical drugs are difficult to use because they tend to cause irritant dermatitis, resulting in exacerbation of the condition. In such cases, treatment should begin with a combination of topical corticosteroid therapy and oral antifungal drugs active against dermatophytes. Topical antifungal drugs are used after the complications resolve. A combination of topical and oral antifungal drugs can shorten the treatment period, thus improving patient adherence to topical treatment. Oral antifungal drugs are useful because of their wide range of applications in the treatment of dermatomycosis. PMID:27251319

  7. Eight-drug/radiation therapy program (MOPP/ABDV/RT) for advanced Hodgkin's disease

    SciTech Connect

    Straus, D.J.; Myers, J.; Passe, S.

    1980-07-15

    Eighty-four evaluable patients with advanced Hodgkin's disease (Stages IIB, IIIA age > 35 or mixed cellularity or lymphocyte depletion histology, IIIB, IVA, and IVB) were treated with alternating monthly MOPP and Adriamycin, bleomycin, dacarbazine, and vinblastine (ABDV). Radiation therapy (RT), 2000 rads in two weeks, was given to areas of initial bulky disease in untreated patients. Complete remission (CR) rates were 80% for previously untreated, 65% for prior RT or minimal chemotherapy treated, and 50% for heavily pretreated patients. Among 49 previously untreated patients there were no primary treatment failures. The estimated two-year relapse rate for the CR group was 9%. The therapeutic effectiveness of this program may have been due to either or both of the following elements: (1) two non-cross-resistant drug combinations; (2) low dose adjuvant RT to initial sites of bulky disease. These early results are among the best reported for the treatment of advanced Hodgkin's disease.

  8. Rural drug users: factors associated with substance abuse treatment utilization.

    PubMed

    Oser, Carrie B; Leukefeld, Carl G; Tindall, Michele Staton; Garrity, Thomas F; Carlson, Robert G; Falck, Russel; Wang, Jichuan; Booth, Brenda M

    2011-06-01

    The purpose of this study is to use a modified version of Andersen's Behavioral Model of Health Services Use to identify the correlates of the number of substance abuse treatment episodes received by rural drug users. Data were collected from face-to-face interviews with 711 drug users in rural areas of Ohio, Arkansas, and Kentucky. Descriptive analyses examine rural drug users' substance use histories and retrospective substance abuse treatment service utilization patterns. A negative binomial regression model indicated that selected predisposing, historical health, and enabling factors were significantly associated with the utilization of substance abuse treatment among rural drug users. Despite high levels of recent and lifetime self-reported substance use among these rural drug users, treatment services were underutilized. Future studies are needed to examine the impact of the health care system and characteristics of the external environment associated with rural substance abuse treatment in order to increase utilization among drug users.

  9. Factors related to psychosocial barriers to drug treatment among Chinese drug users.

    PubMed

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

    2014-08-01

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

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

    ERIC Educational Resources Information Center

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

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

  11. New and emerging targeted treatments in advanced non-small-cell lung cancer.

    PubMed

    Hirsch, Fred R; Suda, Kenichi; Wiens, Jacinta; Bunn, Paul A

    2016-09-01

    Targeted therapies are substantially changing the management of lung cancers. These treatments include drugs that target driver mutations, those that target presumed important molecules in cancer cell proliferation and survival, and those that inhibit immune checkpoint molecules. This area of research progresses day by day, with novel target discoveries, novel drug development, and use of novel combination treatments. Researchers and clinicians have also extensively investigated the predictive biomarkers and the molecular mechanisms underlying inherent or acquired resistance to these targeted therapies. We review recent progress in the development of targeted treatments for patients with advanced non-small-cell lung cancer, especially focusing on data from published clinical trials. PMID:27598681

  12. Drug treatment of psychiatric patients in general practice.

    PubMed

    Tyrer, P

    1978-10-01

    The prescribing of psychotropic drugs by general practitioners was assessed by analysing the drug treatment of all patients referred from general practice to a psychiatric outpatient clinic over four years. Of the 287 patients, 220 were taking one or more of 56 different psychotropic drugs at referral, diazepam being the most common. Benzodiazepines and barbiturates had been taken for significantly longer than other drugs, and, of a total of 342 drugs, 61 had been prescribed regularly for over a year. Half of the drugs were considered to be incorrectly prescribed on pharmacological grounds, the main errors being unnecessarily prolonged regular treatment, incorrect dosage (particularly common with antidepressants), and polypharmacy with drugs of similar pharmacological action. A basic grounding in the pharmacology of psychotropic drugs might help practitioners to avoid prescribing errors of this kind.

  13. Systematic Structure Modifications of Multi-target Prostate Cancer Drug Candidate Galeterone to Produce Novel Androgen Receptor Down-regulating Agents as an Approach to Treatment of Advanced Prostate Cancer

    PubMed Central

    Purushottamachar, Puranik; Godbole, Abhijit M.; Gediya, Lalji K.; Martin, Marlena S.; Vasaitis, Tadas S.; Kwegyir-Afful, Andrew K.; Ramalingam, Senthilmurugan; Ates-Alagoz, Zeynep; Njar, Vincent C. O.

    2013-01-01

    As part of our program to explore the influence of small structural modifications of our drug candidate, 3β-(hydroxy)-17-(1H-benzimidazol-1-yl)-androsta-5,16-diene (galeterone, 5) on the modulation of the androgen receptor (AR), we have prepared and evaluated a series of novel C-3, C-16 and C-17 analogs. Using structure activity analysis, we established that the benzimidazole moiety at C-17 is essential and optimal and also that hydrophilic and heteroaromatic groups at C-3 enhance both anti-proliferative (AP) and AR degrading (ARD) activities. The most potent anti-proliferative compounds were 3β-(1H-imidazole-1-carboxylate)- 17-(1H-benzimidazol-1-yl)-androsta-5,16-diene (47), 3-((EZ)-hydroximino)-17-(1Hbenzimidazol- 1-yl)-androsta-4,16-diene (36), 3β-(pyridine-4-carboxylate)-17-(1H-benzimidazol- 1-yl)-androsta-5,16-diene (43), with GI50 values of 0.87, 1.91 and 2.57 μM, respectively. Compared to 5, compound 47 was 4- and 8-fold more potent with respect to AP and ARD activities, respectively. Importantly, we also discovered that our compounds, including 5, 36, 43 and 47 could degrade both full-length and truncated AR in CWR22rv1 human prostate cancer cells. With these activities, their potential for development as new drugs for the treatment of all forms of prostate cancer. PMID:23713567

  14. Some Advanced Kidney Cancer Patients May Postpone Treatment

    MedlinePlus

    ... advanced kidney cancer that has spread require immediate, aggressive treatment, a small new study suggests. "A subset ... them the inconvenience and debilitating side effects of aggressive treatments for about a year, and in some ...

  15. Predictors of Successful Completion of a Postincarceration Drug Treatment Program.

    ERIC Educational Resources Information Center

    Hohman, Melinda M.; McGaffigan, Richard P.; Segars, Lance

    2000-01-01

    Study compares the characteristics of 1,763 parolees with substance abuse problems who successfully completed a postincarceration drug treatment program. Those who completed the program were more likely to be women who had not used drugs 30 days before program admission, had fewer prior treatment experiences, remained in the program longer, and…

  16. Psychological Symptoms and Drug Use Severity among Israeli Adolescents Presenting for Outpatient Drug Abuse Treatment

    ERIC Educational Resources Information Center

    Diamond, G.M.; Izzard, M.C.; Kedar, T.; Hutlzer, A.; Mell, H.

    2005-01-01

    The objective of this study was to assess the rates of externalizing and internalizing symptoms, and the relation between psychological symptoms and drug use severity, among 117 Israeli adolescents presenting for outpatient drug abuse treatment. Psychological symptoms were assessed via both adolescent self-report and parent report. Drug use was…

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

    ERIC Educational Resources Information Center

    Brown, Randall

    2011-01-01

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

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

    PubMed Central

    Everitt, Barry J

    2014-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  20. Sex differences in drug abuse: Etiology, prevention, and treatment.

    PubMed

    Evans, Suzette M; Reynolds, Brady

    2015-08-01

    This special issue exemplifies one of the major goals of the current editor of Experimental and Clinical Psychopharmacology (Dr. Suzette Evans): to increase the number of manuscripts that emphasize females and address sex differences. Taken together, these articles represent a broad range of drug classes and approaches spanning preclinical research to treatment to better understand the role of sex differences in drug abuse. While not all studies found sex differences, we want to emphasize that finding no sex difference is just as important as confirming one, and should be reported in peer-reviewed journals. It is our intention and hope that this special issue will further advance scientific awareness about the importance of accounting for sex differences in the study of substance abuse. Participant sex is an essential variable to consider in developing a more comprehensive understanding of substance abuse. Rather than viewing investigating sex differences as burdensome, investigators should seize this opportune area ripe for innovative research that is long overdue. PMID:26237316

  1. Recent advances in the diagnosis and treatment of childhood tuberculosis

    PubMed Central

    Kumar, Mani Kant; Kumar, Prashant; Singh, Anjali

    2015-01-01

    Despite over 2.3 million (26% of global burden) cases of tuberculosis (TB) in India the accurate diagnosis of childhood TB remains a major challenge. Children with TB usually have paucibacillary disease and contribute little to disease transmission within the community. Consequently the treatment of children with TB is often not considered a priority by TB control programmes. Adequate and timely assessment of TB infection in childhood could diminish epidemiological burden as underdiagnosed pediatric patients can eventually evolve in to an active state and have the potential to disseminate the etiological agent Mycobacterium tuberculosis, notably increasing this worldwide public health problem. In this review we discuss the most important recent advances in the diagnosis of childhood TB: (1) Symptom-based approaches, (2) novel immune-based approaches, including in vitro interferon-γ IGRA release assays IGRA tests; and (3) bacteriological and molecular methods that are more rapid and/or less expensive than conventional culture techniques for TB diagnosis and/or drug-resistance testing. Recent advances have improved our ability to diagnose latent infection and active TB in children, nevertheless establishing a diagnosis of either latent infection or active disease in HIV-infected children remains a major challenge. PMID:26283820

  2. Recent advances in the diagnosis and treatment of childhood tuberculosis.

    PubMed

    Kumar, Mani Kant; Kumar, Prashant; Singh, Anjali

    2015-01-01

    Despite over 2.3 million (26% of global burden) cases of tuberculosis (TB) in India the accurate diagnosis of childhood TB remains a major challenge. Children with TB usually have paucibacillary disease and contribute little to disease transmission within the community. Consequently the treatment of children with TB is often not considered a priority by TB control programmes. Adequate and timely assessment of TB infection in childhood could diminish epidemiological burden as underdiagnosed pediatric patients can eventually evolve in to an active state and have the potential to disseminate the etiological agent Mycobacterium tuberculosis, notably increasing this worldwide public health problem. In this review we discuss the most important recent advances in the diagnosis of childhood TB: (1) Symptom-based approaches, (2) novel immune-based approaches, including in vitro interferon-γ IGRA release assays IGRA tests; and (3) bacteriological and molecular methods that are more rapid and/or less expensive than conventional culture techniques for TB diagnosis and/or drug-resistance testing. Recent advances have improved our ability to diagnose latent infection and active TB in children, nevertheless establishing a diagnosis of either latent infection or active disease in HIV-infected children remains a major challenge.

  3. [Circadian rhythm study from anticipatory behavior to drug treatment].

    PubMed

    Shibata, Shigenobu

    2005-10-01

    Precise, rhythmic, daily change of the internal milieu is a conspicuous feature of all living organisms. It affects temporal patterns of all kinds of behaviors during a day and deeply influences both the social structure and daily life of individual human beings. These daily variations arise from the internal circadian mechanisms. Three functions of the endogenous clock are discriminated as rhythm generation, entrainment to light-dark cycle and output from the clock. The endogenous clock is localized in the suprachiasmatic nucleus (SCN) in mammals. Recent papers demonstrated strong expression of clock genes such as Per1, Per2 and Per3 in the SCN. Circadian oscillation is basically regulated by the transcription/translation feedback system of the Per gene in mammals. As serotonin/antidepressant and GABA/benzodiazepine drugs affect the light and non-light-induced entrainment, these drugs can regulate the circadian oscillation of clock genes and environmental stimuli-induced change of Per gene expression in the SCN. There are two main stimuli that entrain circadian rhythm, the light-dark cycle (LD) and restricted feeding. Light resets the circadian clock with induction of Per1 and Per2 gene in the SCN, the locus of a main oscillator. Mice were allowed access to food for 4 h during daytime (7 h in advance of feeding time) under LD or constant darkness. The peaks of mPer1 and mPer2 mRNA in the cerebral cortex and liver were advanced 6-12 h after 6 days of RF, whereas those in SCN were unaffected. The increase of mPer expression by RF treatment was observed in SCN-lesioned mice. The present results suggest that RF strongly entrained the expression of mPer and clock-controlled genes in the cerebral cortex and liver without affecting light-dependent SCN clock function.

  4. Rejecting the evidence: Russia's drug dependence treatment system.

    PubMed

    Lohman, Diederik

    2008-12-01

    In at least three regions of Russia, the drug treatment system fails to respond to the needs of injection drug users seeking treatment for their addiction. In this article, based on his presentation at a concurrent session at the conference, Diederik Lohman describes the results of research conducted by Human Rights Watch (HRW). The author explains that the Russian medical establishment ignores overwhelming scientific evidence that treatment substitution programs are both safe and effective.

  5. Nivolumab-Based Treatments for Advanced Melanoma

    Cancer.gov

    A summary of results from an international, double-blind, randomized phase III trial testing the combination of nivolumab (Opdivo®) and ipilimumab (Yervoy®) against nivolumab alone and ipilimumab alone in patients with advanced melanoma.

  6. 75 FR 48356 - Advancing the Development of Medical Products Used In the Prevention, Diagnosis, and Treatment of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-10

    ... HUMAN SERVICES Food and Drug Administration Advancing the Development of Medical Products Used In the Prevention, Diagnosis, and Treatment of Neglected Tropical Diseases; Public Hearing; Change of Hearing Date and Location AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

  7. Clinical Neuroprotective Drugs for Treatment and Prevention of Stroke

    PubMed Central

    Kikuchi, Kiyoshi; Uchikado, Hisaaki; Morioka, Motohiro; Murai, Yoshinaka; Tanaka, Eiichiro

    2012-01-01

    Stroke is an enormous public health problem with an imperative need for more effective therapies. In therapies for ischemic stroke, tissue plasminogen activators, antiplatelet agents and anticoagulants are used mainly for their antithrombotic effects. However, free radical scavengers, minocycline and growth factors have shown neuroprotective effects in the treatment of stroke, while antihypertensive drugs, lipid-lowering drugs and hypoglycemic drugs have shown beneficial effects for the prevention of stroke. In the present review, we evaluate the treatment and prevention of stroke in light of clinical studies and discuss new anti-stroke effects other than the main effects of drugs, focusing on optimal pharmacotherapy. PMID:22837724

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

    PubMed Central

    Soekmadji, Carolina; Nelson, Colleen C.

    2015-01-01

    Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers. In cancer treatment, development of acquired drug resistance phenotype is a serious issue. Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance. EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells. In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer. The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed. Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs. PMID:26587537

  9. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2014.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2015-02-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2014. Studies on food allergy suggest worrisomely high rates of peanut allergy and food-induced anaphylaxis-related hospitalizations. Evidence is mounting to support the theory that environmental exposure to peanut, such as in house dust, especially with an impaired skin barrier attributed to atopic dermatitis (AD) and loss of function mutations in the filaggrin gene, is a risk factor for sensitization and allergy. Diagnostic tests are improving, with early studies suggesting the possibility of developing novel cellular tests with increased diagnostic utility. Treatment trials continue to show the promise and limitations of oral immunotherapy, and mechanistic studies are elucidating pathways that might define the degree of efficacy of this treatment. Studies have also provided insights into the prevalence and characteristics of anaphylaxis and insect venom allergy, such as suggesting that baseline platelet-activating factor acetylhydrolase activity levels are related to the severity of reactions. Advances in drug allergy include identification of HLA associations for penicillin allergy and a microRNA biomarker/mechanism for toxic epidermal necrolysis. Research identifying critical events leading to skin barrier dysfunction and the polarized immune pathways that drive AD have led to new therapeutic approaches in the prevention and management of AD.

  10. Anxiety levels and related pharmacological drug treatment: a memorandum for the third millennium.

    PubMed

    Pasquini, Massimo; Berardelli, Isabella

    2009-01-01

    Anxiety disorders frequently affect the general population and have a lifetime prevalence ranging from 13.6% to 28.8%. This paper reviews full articles dealing with the pharmacological treatments of generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), panic disorder (PD) and post-traumatic stress disorder (PTSD). This review also attempts to evaluate the use of new drugs acting on several neurotransmitters involved in the pathophysiology of anxiety disorders. Major advances include the development of glutamatergic drugs for treating GAD and OCD. Further randomized controlled trials to test the effect of glutamatergic agents in the treatment of OCD and GAD would be warranted.

  11. Improving Care for the Treatment of Alcohol and Drug Disorders

    PubMed Central

    McCarty, Dennis; Gustafson, David; Capoccia, Victor A.; Cotter, Frances

    2008-01-01

    The Network for the Improvement of Addiction Treatment (NIATx) teaches alcohol and drug treatment programs to apply process improvement strategies and make organizational changes that improve quality of care. Participating programs reduce days to admission, increase retention in care and spread the application of process improvement within their treatment centers. More generally, NIATx provides a framework for addressing the Institute of Medicine’s six dimensions of quality care (i.e., safe, effective, patient-centered, efficient, timely and equitable) in treatments for alcohol, drug and mental health disorders. NIATx and its extensions illustrate how the behavioral health field can respond to the demand for higher quality treatment services. PMID:18259871

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

    PubMed Central

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

    2012-01-01

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

  13. Advanced materials and processing for drug delivery: the past and the future.

    PubMed

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

    2013-01-01

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

  14. [News and perspectives in the treatment of advanced gastric and colorectal cancers].

    PubMed

    Diciolla, A; Cristina, V; De Micheli, R; Digklia, A; Wagner, A D

    2015-05-20

    Colorectal and gastric cancers are the fourth and third leading causes of cancer death world-wide. Unfortunately, gastric cancer is usually diagnosed at an advanced stage after becoming metastatic in distant sites, so that palliative therapy is the mainstay of treatment. Major progress in the understanding of the biology, the development of valid biomarkers and molecular targeted drugs have improved the treatment options and prognosis of both cancers significantly in the last years. Here, we review the current standards of care for patients with advanced and metastatic colorectal and gastric cancer and outline the perspectives for the future.

  15. Sonidegib, a novel smoothened inhibitor for the treatment of advanced basal cell carcinoma

    PubMed Central

    Doan, Hung Q; Silapunt, Sirunya; Migden, Michael R

    2016-01-01

    Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. If left untreated, BCCs can become locally aggressive or even metastasize. Currently available treatments include local destruction, surgery, and radiation. Systemic options for advanced disease are limited. The Hedgehog (Hh) pathway is aberrantly activated in a majority of BCCs and in other cancers. Hh pathway inhibitors are targeted agents that inhibit the aberrant activation of the Hh pathway, with smoothened being a targeted component. Sonidegib is a novel smoothened inhibitor that was recently approved by the US Food and Drug Administration. This review focuses on BCC pathogenesis and the clinical efficacy of sonidegib for the treatment of advanced BCC. PMID:27695345

  16. Sonidegib, a novel smoothened inhibitor for the treatment of advanced basal cell carcinoma

    PubMed Central

    Doan, Hung Q; Silapunt, Sirunya; Migden, Michael R

    2016-01-01

    Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. If left untreated, BCCs can become locally aggressive or even metastasize. Currently available treatments include local destruction, surgery, and radiation. Systemic options for advanced disease are limited. The Hedgehog (Hh) pathway is aberrantly activated in a majority of BCCs and in other cancers. Hh pathway inhibitors are targeted agents that inhibit the aberrant activation of the Hh pathway, with smoothened being a targeted component. Sonidegib is a novel smoothened inhibitor that was recently approved by the US Food and Drug Administration. This review focuses on BCC pathogenesis and the clinical efficacy of sonidegib for the treatment of advanced BCC.

  17. [Modern drug therapy of atrial fibrillation: selection of treatment strategy, antiarrhythmic preparations, and schemes of treatment].

    PubMed

    Kanorskiĭ, S G

    2012-01-01

    This review presents novel literature data on drug treatment of atrial fibrillation. We discuss here choice of strategy of therapy, antiarrhythmic drugs, and algorithms of preventive measures aimed at prevention of recurrences of this arrhythmia.

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  19. Randomized Trial of Drug Abuse Treatment-Linkage Strategies

    ERIC Educational Resources Information Center

    Sorenson, James L.; Masson, Carmen L.; Delucchi, Kevin; Sporer, Karl; Barnett, Paul G.; Mitsuishi, Fumi; Lin, Christine; Song, Yong; Chen, TeChieh; Hall, Sharon M.

    2005-01-01

    A clinical trial contrasted 2 interventions designed to link opioid-dependent hospital patients to drug abuse treatment. The 126 out-of-treatment participants were randomly assigned to (a) case management, (b) voucher for free methadone maintenance treatment (MMT), (c) case management plus voucher, or (d) usual care. Services were provided for 6…

  20. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2012.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2013-01-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2012. Studies support an increase in peanut allergy prevalence in children and exposure to the antibacterial agent triclosan and having filaggrin (FLG) loss-of-function mutations as risk factors for food sensitization. The role of specific foods in causing eosinophilic esophagitis is elucidated by several studies, and microRNA analysis is identified as a possible noninvasive disease biomarker. Studies on food allergy diagnosis emphasize the utility of component testing and the possibility of improved diagnosis through stepped approaches, epitope-binding analysis, and bioinformatics. Treatment studies of food allergy show promise for oral immunotherapy, but tolerance induction remains elusive, and additional therapies are under study. Studies on anaphylaxis suggest an important role for platelet-activating factor and its relationship to the need for prompt treatment with epinephrine. Insights on the pathophysiology and diagnosis of non-IgE-mediated drug allergy are offered, with novel data regarding the interaction of drugs with HLA molecules. Numerous studies support influenza vaccination of persons with egg allergy using modest precautions. Evidence continues to mount that there is cross-talk between skin barrier defects and immune responses in patients with atopic dermatitis. Augmentation of the skin barrier with reduction in skin inflammatory responses will likely lead to the most effective intervention in patients with this common skin disease.

  1. Recent Advances on Pathophysiology, Diagnostic and Therapeutic Insights in Cardiac Dysfunction Induced by Antineoplastic Drugs

    PubMed Central

    Molinaro, Marilisa; Ameri, Pietro; Marone, Giancarlo; Petretta, Mario; Abete, Pasquale; Di Lisa, Fabio; De Placido, Sabino; Bonaduce, Domenico; Tocchetti, Carlo G.

    2015-01-01

    Along with the improvement of survival after cancer, cardiotoxicity due to antineoplastic treatments has emerged as a clinically relevant problem. Potential cardiovascular toxicities due to anticancer agents include QT prolongation and arrhythmias, myocardial ischemia and infarction, hypertension and/or thromboembolism, left ventricular (LV) dysfunction, and heart failure (HF). The latter is variable in severity, may be reversible or irreversible, and can occur soon after or as a delayed consequence of anticancer treatments. In the last decade recent advances have emerged in clinical and pathophysiological aspects of LV dysfunction induced by the most widely used anticancer drugs. In particular, early, sensitive markers of cardiac dysfunction that can predict this form of cardiomyopathy before ejection fraction (EF) is reduced are becoming increasingly important, along with novel therapeutic and cardioprotective strategies, in the attempt of protecting cardiooncologic patients from the development of congestive heart failure. PMID:26583088

  2. Assessment of AIDS Risk among Treatment Seeking Drug Abusers.

    ERIC Educational Resources Information Center

    Black, John L.; And Others

    Intravenous (IV) drug abusers are at risk for contracting transmittable diseases such as acquired immunodeficiency syndrome (AIDS) and hepatitis B. This study was conducted to investigate the prevalence of risk behaviors for acquiring and transmitting AIDS and hepatitis B among treatment-seeking drug abusers (N=168). Subjects participated in a…

  3. Gender Differences among Israeli Adolescents in Residential Drug Treatment

    ERIC Educational Resources Information Center

    Isralowitz, Richard; Reznik, Alex

    2007-01-01

    Aims: The use of licit and illicit drugs is considered to be primarily a male problem. Numerous studies, however, question the extent of gender differences. This article reports on last 30 day drug use and related problem behaviour among male and female youth prior to residential treatment. Methods: Self-report data were collected from 95 male and…

  4. How Drug Treatment Courts Work: An Analysis of Mediators

    ERIC Educational Resources Information Center

    Gottfredson, Denise C.; Kearley, Brook W.; Najaka, Stacy S.; Rocha, Carlos M.

    2007-01-01

    This study examines program elements related to reductions in drug use and crime among Drug Treatment Courts (DTC) participants as well as theoretical mechanisms--increased social controls and improved perceptions of procedural justice--expected to mediate the effects of DTC on these outcomes. Data are from 157 research participants interviewed…

  5. Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment.

    PubMed

    Kang, Lin; Gao, Zhonggao; Huang, Wei; Jin, Mingji; Wang, Qiming

    2015-05-01

    The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells, which is usually caused by abnormal gene expression. RNA interference mediated by siRNA and miRNA can selectively knock down the carcinogenic genes by targeting specific mRNAs. Therefore, combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy. Due to poor stability and solubility associated with gene agents and drugs, suitable protective carriers are needed and have been widely researched for the co-delivery. In this review, we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents, as well as the advances in co-delivery systems. PMID:26579443

  6. Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment

    PubMed Central

    Kang, Lin; Gao, Zhonggao; Huang, Wei; Jin, Mingji; Wang, Qiming

    2015-01-01

    The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells, which is usually caused by abnormal gene expression. RNA interference mediated by siRNA and miRNA can selectively knock down the carcinogenic genes by targeting specific mRNAs. Therefore, combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy. Due to poor stability and solubility associated with gene agents and drugs, suitable protective carriers are needed and have been widely researched for the co-delivery. In this review, we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents, as well as the advances in co-delivery systems. PMID:26579443

  7. Use of Gestalt Therapy Within a Drug Treatment Program.

    ERIC Educational Resources Information Center

    Sideroff, Stephen I.

    1979-01-01

    Presents a Gestalt therapeutic approach that has shown promise within a drug treatment program. The major issues discussed include the acquisition of self-support, taking responsibility, dealing with anxiety, contact, and the expression of pent-up feelings. (Author)

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  9. Myeloproliferative neoplasms: A decade of discoveries and treatment advances.

    PubMed

    Tefferi, Ayalew

    2016-01-01

    Myeloproliferative neoplasms (MPN) are clonal stem cell diseases, first conceptualized in 1951 by William Dameshek, and historically included chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). In 1960, Nowell and Hungerford discovered an invariable association between the Philadelphia chromosome (subsequently shown to harbor the causal BCR-ABL1 mutation) and CML; accordingly, the term MPN is primarily reserved for PV, ET, and PMF, although it includes other related clinicopathologic entities, according to the World Health Organization (WHO) classification system. In 2005, William Vainchenker and others described a Janus kinase 2 mutation (JAK2V617F) in MPN and this was followed by a series of additional descriptions of mutations that directly or indirectly activate JAK-STAT: JAK2 exon 12, myeloproliferative leukemia virus oncogene (MPL) and calreticulin (CALR) mutations. The discovery of these, mostly mutually exclusive, "driver" mutations has contributed to revisions of the WHO diagnostic criteria and risk stratification in MPN. Mutations other than JAK2, CALR and MPL have also been described in MPN and shown to provide additional prognostic information. From the standpoint of treatment, over the last 50 years, Louis Wasserman from the Unites States and Tiziano Barbui from Italy had skillfully organized and led a number of important clinical trials, whose results form the basis for current treatment strategies in MPN. More recently, allogeneic stem cell transplant, as a potentially curative treatment modality, and JAK inhibitors, as palliative drugs, have been added to the overall therapeutic armamentarium in myelofibrosis. In the current review, I will summarize the important advances made in the last 10 years regarding the science and practice of MPN.

  10. Nanoparticulate drug delivery platforms for advancing bone infection therapies

    PubMed Central

    Uskoković, Vuk; Desai, Tejal A

    2015-01-01

    Introduction The ongoing surge of resistance of bacterial pathogens to antibiotic therapies and the consistently aging median member of the human race signal an impending increase in the incidence of chronic bone infection. Nanotechnological platforms for local and sustained delivery of therapeutics hold the greatest potential for providing minimally invasive and maximally regenerative therapies for this rare but persistent condition. Areas covered Shortcomings of the clinically available treatment options, including poly(methyl methacrylate) beads and calcium sulfate cements, are discussed and their transcending using calcium-phosphate/polymeric nanoparticulate composites is foreseen. Bone is a composite wherein the weakness of each component alone is compensated for by the strength of its complement and an ideal bone substitute should be fundamentally the same. Expert opinion Discrepancy between in vitro and in vivo bioactivity assessments is highlighted, alongside the inherent imperfectness of the former. Challenges entailing the cross-disciplinary nature of engineering a new generation of drug delivery vehicles are delineated and it is concluded that the future for the nanoparticulate therapeutic carriers belongs to multifunctional, synergistic and theranostic composites capable of simultaneously targeting, monitoring and treating internal organismic disturbances in a smart, feedback fashion and in direct response to the demands of the local environment. PMID:25109804

  11. Alternatives to Drug Treatment for Hyperactivity.

    ERIC Educational Resources Information Center

    Den Houtter, Kathryn

    1980-01-01

    Results from recent studies on the effectiveness of Ritalin for "hyperactivity" show that this treatment is dubious at best. This article presents an alternative treatment approach, placing emphasis on devising an appropriate learning situation that meets the needs of the so-called hyperactive child. (Author)

  12. Advances in the treatment of cognitive impairment in Parkinson's disease.

    PubMed

    Goldman, Jennifer G; Weintraub, Daniel

    2015-09-15

    Cognitive impairment in Parkinson's disease (PD) is a frequent complication, with significant interindividual variability in clinical symptoms, severity, timing, and neural substrates. Recent studies have focused not only on understanding PD dementia, but also mild cognitive impairment in PD, which may represent a prodromal stage for dementia. In recent years, there have been important advances regarding clinical characterizations, definitions, associated biomarkers, and risk factors for both mild cognitive impairment in PD and PD dementia. However, there is a paucity of effective therapies for cognitive impairment in PD, whether for mild symptoms or for moderate to severe dementia. At present, only rivastigmine is U.S. Food and Drug Administration approved for PD dementia, an indication received nearly a decade ago. Given the frequency of PD cognitive impairment and its substantial impact on both patients and families, the lack of available and effective treatments represents a striking gap in the field, especially when compared to the large number of available therapies for PD motor symptoms and complications. Improved symptomatic therapies, as well as potential disease-modifying agents, for PD cognitive impairment are needed. Most therapeutic trials for PD dementia and mild cognitive impairment in PD have focused on drugs developed for and tested in Alzheimer's disease, such as cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist, memantine, though recent and ongoing trials examine the effects of pharmacological agents affecting other neurotransmitters, as well as nonpharmacological therapies, including mental and physical exercise and neurostimulation. This review summarizes the design and outcomes of trials for PD cognitive impairment published since 2013 and highlights future therapeutic research opportunities and challenges.

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

    ERIC Educational Resources Information Center

    Taxman, Faye S.; Bouffard, Jeffrey A.

    2005-01-01

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

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

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  15. Gastroretentive drug delivery systems for the treatment of Helicobacter pylori

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Pringle, Abbie; Harmer, Catherine J.

    2015-01-01

    Human models of emotional processing suggest that the direct effect of successful antidepressant drug treatment may be to modify biases in the processing of emotional information. Negative biases in emotional processing are documented in depression, and single or short-term dosing with conventional antidepressant drugs reverses these biases in depressed patients prior to any subjective change in mood. Antidepressant drug treatments also modulate emotional processing in healthy volunteers, which allows the consideration of the psychological effects of these drugs without the confound of changes in mood. As such, human models of emotional processing may prove to be useful for testing the efficacy of novel treatments and for matching treatments to individual patients or subgroups of patients. PMID:26869848

  17. Examining drug treatment program entry of injection drug users: human capital and institutional disaffiliation.

    PubMed

    Lundgren, Lena M; Schilling, Robert F; Ferguson, Faith; Davis, Karen; Amodeo, Maryann

    2003-05-01

    Logistic regression analysis was used to examine the likelihood of either entering residential treatment, methadone treatment or solely entering detoxification programs for 32,173 injection drug users (IDUs) using drug treatment in Massachusetts, 1996-1999. Those IDUs who were employed, more educated, health-insured, not homeless and who resided with their children were less likely to solely enter detoxification programs. This population, with more human capital and lower levels of institutional disaffiliation, was also more likely to enter methadone maintenance programs. These results were consistent for two groups of drug users: those who reported having injected in the past year and those with a history of injecting who had not injected in the past year. Overall, the findings demonstrate a need for more complex drug treatment program planning efforts that also respond to issues of employment, education and social isolation.

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

    PubMed

    Pringle, Abbie; Harmer, Catherine J

    2015-12-01

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

  19. Predicting drug court treatment completion using the MMPI-2-RF.

    PubMed

    Mattson, Curtis; Powers, Bradley; Halfaker, Dale; Akeson, Steven; Ben-Porath, Yossef

    2012-12-01

    We examined the ability of the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008) substantive scales to predict Drug Court treatment completion in a sample of individuals identified as being at risk for failure to complete the program. Higher scores on MMPI-2-RF scales Behavior/Externalizing Dysfunction, Antisocial Behavior, Aberrant Experiences, Juvenile Conduct Problems, Aggression, and Disconstraint-Revised were associated with increased risk for failure to complete treatment. These results are consistent with previous findings (O'Reilly, 2007; Sellbom, Ben-Porath, Baum, Erez, & Gregory, 2008) regarding treatment completion. Gender was also found to be associated with treatment completion, with females being more likely to complete the Drug Court program than males. Zero-order correlations and relative risk analyses indicated that the MMPI-2-RF can provide useful information regarding risk factors for failure to complete Drug Court treatment. Limitations and future directions are discussed.

  20. Factors related to drug treatment refusal in a forensic hospital.

    PubMed

    Rodenhauser, P; Schwenkner, C E; Khamis, H J

    1987-06-01

    Using the hospital records of 421 patients in a maximum-security forensic hospital, the authors explored the relationship between clinical factors and patients' receptiveness to or refusal of drug treatment. They found drug treatment refusal to be significantly related to a psychotic diagnosis in the absence of a personality disorder; in contrast, psychotic patients with personality disorders tended to be relatively compliant with drug treatment. Treatment refusers had significantly longer lengths of hospitalization that were not reduced by receipt of medication. Significant relationships were also found between treatment refusal and involuntary medication, use of restraints, and greater number of previous hospitalizations; between reasons for refusal and involuntary medication; and between history of substance abuse and previous incarceration.

  1. Viral hemorrhagic fevers: advancing the level of treatment

    PubMed Central

    2012-01-01

    The management of viral hemorrhagic fevers (VHFs) has mainly focused on strict infection control measures, while standard clinical interventions that are provided to patients with other life-threatening conditions are rarely offered to patients with VHFs. Despite its complexity, a proper clinical case management of VHFs is neither futile nor is it lacking in scientific rationale. Given that patient outcomes improve when treatment is started as soon as possible, development and implementation of protocols to promptly identify and treat patients in the earliest phases of diseases are urgently needed. Different pharmacological options have been proposed to manage patients and, as for other life-threatening conditions, advanced life support has been proved effective to address multiorgan failure. In addition, high throughput screening of small molecular libraries has emerged as a novel promising way to find new candidates drugs for VHFs therapy and a relevant number of new molecules are currently under investigation. Here we discuss the current knowledge about VHF clinical management to propose a way to step up the approach to VHFs beyond the mere application of infection control measures. PMID:22458265

  2. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insect stings.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2004-07-01

    This review highlights some of the research advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insect venom that were reported primarily in the Journal of Allergy and Clinical Immunology from 2002 through 2003. Among the topics highlighted are new insights into the pathogenesis of atopic dermatitis and potential strategies for more effective treatment of the atopic march. Patients should remain supine with raised legs during anaphylactic shock because upper body elevation could result in sudden death from loss of venous return to the heart. A major advance in food allergy was that humanized, monoclonal anti-IgE antibody showed protection against peanut-induced anaphylaxis. In addition to studies elucidating mechanisms of drug hypersensitivity, a clinical study showed patients with a history of prior penicillin allergy with negative penicillin allergy test results are unlikely to experience reactions or resensitization on subsequent oral courses of penicillin. Lastly, there are new recommendations for patients with convincing insect sting reaction histories but negative skin test responses to venom.

  3. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2010.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2011-02-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin disease that were reported in the Journal in 2010. Key epidemiologic observations include an apparent increase in peanut allergy, with more than 1% of children affected, and increasing evidence that early food allergen exposure, rather than avoidance, might improve allergy outcomes. Advances in food allergy diagnosis include improved insights into prognosis and estimation of severity through component-resolved diagnostics and characterization of IgE binding to specific epitopes. Regarding treatment, oral and epicutaneous immunotherapy show promise. Studies of drug allergies show insights into pathophysiology, and studies on insect hypersensitivity reveal improved diagnostic methods. Genetic and functional studies have revealed the important role of epidermal differentiation products in the pathogenesis of atopic dermatitis. Cross-talk between the atopic immune response with the innate immune response have also been found to predispose to infection in patients with atopic dermatitis. New therapeutic approaches to control chronic urticaria have also been identified during the past year.

  4. Pharmacogenetics and individualizing drug treatment during pregnancy

    PubMed Central

    Haas, David M

    2014-01-01

    Pharmacogenetics as a tool to aid clinicians implement individualized pharmacotherapy is utilized in some areas of medicine. Pharmacogenetics in pregnancy is still a developing field. However, there are several areas of obstetric therapeutics where data are emerging that give glimpses into future therapeutic possibilities. These include opioid pain management, antihypertensive therapy, antidepressant medications, preterm labor tocolytics, antenatal corticosteroids and drugs for nausea and vomiting of pregnancy, to name a few. More data are needed to populate the therapeutic models and to truly determine if pharmacogenetics will aid in individualizing pharmacotherapy in pregnancy. The objective of this review is to summarize current data and highlight research needs. PMID:24329192

  5. Pharmacogenetics and individualizing drug treatment during pregnancy.

    PubMed

    Haas, David M

    2014-01-01

    Pharmacogenetics as a tool to aid clinicians implement individualized pharmacotherapy is utilized in some areas of medicine. Pharmacogenetics in pregnancy is still a developing field. However, there are several areas of obstetric therapeutics where data are emerging that give glimpses into future therapeutic possibilities. These include opioid pain management, antihypertensive therapy, antidepressant medications, preterm labor tocolytics, antenatal corticosteroids and drugs for nausea and vomiting of pregnancy, to name a few. More data are needed to populate the therapeutic models and to truly determine if pharmacogenetics will aid in individualizing pharmacotherapy in pregnancy. The objective of this review is to summarize current data and highlight research needs.

  6. 28 CFR 550.52 - Non-residential drug abuse treatment services.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  7. 28 CFR 550.52 - Non-residential drug abuse treatment services.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  8. 28 CFR 550.52 - Non-residential drug abuse treatment services.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  9. 28 CFR 550.52 - Non-residential drug abuse treatment services.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  10. Behavior therapy in drug abuse treatment: review and evaluation.

    PubMed

    Stitzer, M L; Bigelow, G E; McCaul, M E

    1985-01-01

    The goal of drug abuse treatment is to decrease the dominance of drug-related behaviors while enhancing the dominance of alternative socially acceptable behaviors. The behavioral techniques of extinction, satiation, and punishment can be used to suppress undesirable behaviors, and reinforcement can be used to enhance desirable behaviors. Methadone maintenance offers unique advantages for treatment of opiate abuse since methadone satiates the drug abuser, thereby reducing the reinforcing efficacy of illicit opiate drugs, while also serving as a reinforcer whose delivery in the treatment setting can be used in contingent arrangements. Short-term efficacy has been demonstrated in studies that used contingent treatment termination or contingent dose decreases as punishing events and contingent dose increases or contingent take-home privileges as reinforcing events to promote reductions in drug use and cooperation with clinic rules. Systematic use of dose adjustments and take-home privileges may be a useful adjunct to methadone maintenance treatment, having a positive impact both on client outcomes and clinic operation. Rehabilitation efforts might also benefit if delivery of reinforcers available at the clinic is contingent upon participation in skills training and therapy programs or community activities outside the drug abuse clinic. PMID:3929125

  11. Drug treatment of obesity in cardiovascular disease.

    PubMed

    Charakida, Marietta; Finer, Nicholas

    2012-04-01

    Obesity is a significant health problem worldwide and is associated with a number of co-morbidities including type 2 diabetes mellitus, hypertension, dyslipidemia, obstructive sleep apnea, and cardiovascular disease. A number of different pathophysiologic mechanisms including increased inflammation, oxidative stress, and insulin resistance have been associated with initiation and progression of atherosclerotic disease in obese individuals. Lifestyle modifications have provided modest results in weight reduction and the focus of interest has now shifted towards drug development to treat severely obese individuals with a body mass index (BMI) >30 kg/m(2) or those with a BMI >27 kg/m(2) who have additional co-morbidities. Different regimens focusing on dietary absorption or acting centrally to control hunger and food intake have been developed. However, their weight loss effect is, in most cases, modest and this effect is lost once the medication is discontinued. In addition, long-term use of these drugs is limited by significant side effects and lack of long-term safety and efficacy data. Orlistat is the only US FDA-approved medication for long-term use. A number of new medications are currently under investigation in phase III trials with promising preliminary results. This review comments on available anti-obesity pharmacologic regimens, their weight-loss benefit, and their impact on cardiovascular risk factors. PMID:22292446

  12. Fears about treatment among young drug abusers in Hong Kong.

    PubMed

    Chung, Yida Y H; Shek, Daniel T L

    2011-01-01

    This study examined fears about drug treatment among 300 young male heroin abusers in Hong Kong (172 newcomers and 128 repeaters) recruited from non-government treatment agencies. An indigenous 35-item Fears about Treatment Scale (Fears Scale) was developed to measure fears about treatment among the participants. Results showed that four factors (fear of failure, fear of labeling or disclosure, fear of maladaptation and fear of withdrawal) were abstracted from the scale. Reliability analyses showed that subscales based on these four factors and the total scale were internally consistent. The findings showed that treatment failure was the major fear in the respondents. The present findings suggest that drug treatment and rehabilitation services should help clients, particularly young substance abusers, mitigate their treatment fears.

  13. Drug and Alcohol Abuse: Implications for Treatment. Treatment Research Monograph Series.

    ERIC Educational Resources Information Center

    Gardner, Stephen E., Ed.

    Articles in this monograph examine key issues in combined drug and alcohol use. The first chapter discusses clinical and research evidence about the physical and psychological effects of various drug and alcohol combinations. Chapter Two presents findings about usage patterns of alcohol and drugs. The impact of alcohol use in a treatment setting…

  14. Recent Advances in Drug Design and Drug Discovery for Androgen- Dependent Diseases.

    PubMed

    Cabeza, Marisa; Sánchez-Márquez, Araceli; Garrido, Mariana; Silva, Aylín; Bratoeff, Eugene

    2016-01-01

    This article summarizes the importance of different targets such as 5α-reductase, 17β-HSD, CYP17A, androgen receptor and protein kinase A for the treatment of prostate cancer and benign prostatic hyperplasia. It is a well known fact that dihydrotestosterone (DHT) is associated with the development of androgen-dependent afflictions. At the present time, several research groups are attempting to develop new steroidal and non-steroidal molecules with the purpose of inhibiting the synthesis and biological response of DHT. This review also discusses the most recent studies reported in the literature that describe the therapeutic potential of novel compounds, as well as the new drugs, principally inhibitors of 5α-reductase. PMID:26861003

  15. Emerging drugs for migraine prophylaxis and treatment.

    PubMed

    Bigal, Marcelo E; Krymchantowski, Abouch V

    2006-05-04

    Migraine is a chronic neurologic disorder with heterogeneous characteristics resulting in a range of symptom profiles, burden, and disability. Migraine affects nearly 12% of the adult population in occidental countries, imposing considerable economic and social losses. The pharmacologic treatment of migraine includes preventive and acute strategies. A better understanding of the migraine pathophysiology along with the discovery of novel molecular targets has lead to a growing number of upcoming therapeutic proposals. This review focuses on new and emerging agents for the treatment of migraine.

  16. HER2-positive advanced breast cancer: optimizing patient outcomes and opportunities for drug development

    PubMed Central

    Singh, J C; Jhaveri, K; Esteva, F J

    2014-01-01

    Effective targeting of the human epidermal growth factor receptor 2 (HER2) has changed the natural history of HER2 overexpressing (HER2+) metastatic breast cancer. The initial success of trastuzumab improving time to progression and survival rates led to the clinical development of pertuzumab, ado-trastuzumab emtansine and lapatinib. These biologic therapies represent significant additions to the breast medical oncology armamentarium. However, drug resistance ultimately develops and most tumours progress within 1 year. Ongoing studies are evaluating novel therapeutic approaches to overcome primary and secondary drug resistance in tumours, including inhibition of PI3K/TOR, HSP90, IGF-IR and angiogenesis. Mounting experimental data support the clinical testing of immune checkpoint modulators and vaccines. The central nervous system remains a sanctuary site for HER2+ breast cancer and further studies are needed for the prevention and treatment of brain metastases in this population. Despite efforts to identify predictors of preferential benefit from HER2-targeted therapies (e.g., truncated HER2, PTEN loss and SRC activation), HER2 protein overexpression and/or gene amplification remains the most important predictive factor of response to HER2-targeted therapies. In this article, we review the optimal sequence of HER2-targeted therapies and describe ongoing efforts to improve the outcome of HER2+ advanced breast cancer through rational drug development. PMID:25025958

  17. Promising Practices in Drug Treatment: Findings from Latin America

    ERIC Educational Resources Information Center

    Nemes, Susanna; Libretto, Salvatore; Garrett, Gerald; Johansson, Anna Carin; Hess, Lauren

    2005-01-01

    In a study to evaluate the drug treatment and aftercare efforts sponsored by the State Department's International Narcotics and Law Enforcement Affairs Bureau, residential Therapeutic Community (TC) treatment programs in three Latin American countries--Brazil, Peru and Argentina--were examined to identify promising practices and to assess lessons…

  18. Promising Practices in Drug Treatment: An Overview of Methodology

    ERIC Educational Resources Information Center

    Garrett, Gerald; Nemes, Susanna; Hoffman, Jeffrey; Libretto, Salvatore; Skinstadt, Anne Helene; Hess, Lauren

    2005-01-01

    This paper describes a research project sponsored and funded by the State Department's Bureau of International Narcotics and Affairs (INL) on substance abuse and treatment in ten countries. The purpose of the study was to identify promising practices in drug treatment in Europe, Latin America, and Southeast Asia. The steps taken to complete this…

  19. Promising Practices in Drug Treatment: Findings from Europe

    ERIC Educational Resources Information Center

    Nemes, Susanna; Libretto, Salvatore; Skinstad, Anne Helene; Garrett, Gerald; Hoffman, Jeffrey A.

    2005-01-01

    In a study to evaluate the drug treatment and aftercare efforts sponsored by the State Department's International Narcotics and Law Enforcement Affairs Bureau, residential Therapeutic Community (TC) treatment programs in four European countries-Poland, Spain, Slovenia, and Italy-were examined to identify promising practices and to assess lessons…

  20. Promising Practices in Drug Treatment: Findings from Southeast Asia

    ERIC Educational Resources Information Center

    Libretto, Salvatore; Nemes, Susanna; Namur, Jenny; Garrett, Gerald; Hess, Lauren; Kaplan, Linda

    2005-01-01

    In a study to evaluate the drug treatment and aftercare efforts sponsored by the State Department's International Narcotics and Law Enforcement Affairs Bureau, residential Therapeutic Community (TC) treatment programs in three countries in Southeast Asia--Malaysia, Singapore, and Thailand--were examined to identify promising practices and to…

  1. Recent Advances in the Treatment of Organophosphorous Poisonings

    PubMed Central

    Balali-Mood, Mahdi; Saber, Hamidreza

    2012-01-01

    Organophosphorous compounds have been employed as pesticides and chemical warfare nerve agents. Toxicity of organophosphorous compounds is a result of excessive cholinergic stimulation through inhibition of acetyl cholinesterase. Clinical manifestations include cholinergic syndromes, central nervous system and cardiovascular disorders. Organophosphorous pesticide poisonings are common in developing worlds including Iran and Sri Lanka. Nerve agents were used during the Iraq-Iran war in 1983-1988 and in a terrorist attack in Japan in 1994-1995. Following decontamination, depending on the severity of intoxication the administration of atropine to counteract muscarinic over-stimulation, and an oxime to reactivate acetyl cholinesterase are indicated. Supportive and intensive care therapy including diazepam to control convulsions and mechanical respiration may be required. Recent investigations have revealed that intravenous infusion of sodium bicarbonate to produce mild to moderate alkalinization is effective. Gacyclidine; an antiglutamatergic compound, was also proved to be beneficial in conjunction with atropine, pralidoxime, and diazepam in nerve agent poisoning. Intravenous magnesium sulfate decreased hospitalization duration and improved outcomes in patients with organophosphorous poisoning. Bio-scavengers including fresh frozen plasma or albumin have recently been suggested as a useful therapy through clearing of free organophosphates. Hemofiltration and antioxidants are also suggested for organophosphorous poisoning. Recombinant bacterial phosphotriesterases and hydrolases that are able to transfer organophosphorous-degrading enzymes are very promising in delayed treatment of organophosphorous poisoning. Recently, encapsulation of drugs or enzymes in nanocarriers has also been proposed. Given the signs and symptoms of organophosphorous poisoning, health professionals should remain updated about the recent advances in treatment of organophosphorous poisoning

  2. Elimination of drugs of abuse and their toxicity from natural waters by photo-Fenton treatment.

    PubMed

    Catalá, M; Domínguez-Morueco, N; Migens, A; Molina, R; Martínez, F; Valcárcel, Y; Mastroianni, N; López de Alda, M; Barceló, D; Segura, Y

    2015-07-01

    This paper investigates the elimination of drugs of abuse from six different chemical classes and their metabolites in natural fluvial waters (nearby the output of a sewage system). Mineralization of these substances and toxicological characterization before and after treatment by a heterogeneous photo-Fenton system has been evaluated. This advanced oxidation technology was able to significantly reduce the concentration of the drugs of abuse in all the tested conditions (different hydrogen peroxide and catalyst loadings). However, toxicological analyses measured as inhibition of fern spore mitochondrial activity, showed only a complete elimination of acute and chronic toxicity when a higher solid catalyst loading was used (0.6 g/L). A lower catalyst loading of 0.2 g/L was not enough for toxicity elimination. These results evidence the need for combining toxicological tests and chemical analyses in order to establish the effectiveness of the water treatment technologies based on advanced oxidation processes. PMID:25817756

  3. Limited Uptake of Hepatitis C Treatment among Injection Drug Users

    PubMed Central

    Mehta, Shruti H.; Genberg, Becky L.; Astemborski, Jacquie; Kavasery, Ravi; Kirk, Gregory D.; Vlahov, David; Strathdee, Steffanie A.; Thomas, David L.

    2013-01-01

    We characterized HCV treatment knowledge, experience and barriers in a cohort of community-based injection drug users (IDUs) in Baltimore, MD. In 2005, a questionnaire on HCV treatment knowledge, experience and barriers was administered to HCV-infected IDUs. Self-reported treatment was confirmed from medical records. Of 597 participants, 71% were male, 95% African-American, 31% HIV co-infected and 94% were infected with HCV genotype 1; 70% were aware that treatment was available, but only 22% understood that HCV could be cured. Of 418 who had heard of treatment, 86 (21%) reported an evaluation by a provider that included a discussion of treatment of whom 30 refused treatment, 20 deferred and 36 reported initiating treatment (6% overall). The most common reasons for refusal were related to treatment-related perceptions and a low perceived need of treatment. Compared to those who had discussed treatment with their provider, those who had not were more likely to be injecting drugs, less likely to have health insurance, and less knowledgeable about treatment. Low HCV treatment effectiveness was observed in this IDU population. Comprehensive integrated care strategies that incorporate education, case-management and peer support are needed to improve care and treatment of HCV-infected IDUs. PMID:18165889

  4. Limited uptake of hepatitis C treatment among injection drug users.

    PubMed

    Mehta, Shruti H; Genberg, Becky L; Astemborski, Jacquie; Kavasery, Ravi; Kirk, Gregory D; Vlahov, David; Strathdee, Steffanie A; Thomas, David L

    2008-06-01

    We characterized hepatitis C virus (HCV) treatment knowledge, experience and barriers in a cohort of community-based injection drug users (IDUs) in Baltimore, MD. In 2005, a questionnaire on HCV treatment knowledge, experience and barriers was administered to HCV-infected IDUs. Self-reported treatment was confirmed from medical records. Of 597 participants, 71% were male, 95% African-American, 31% HIV co-infected and 94% were infected with HCV genotype 1; 70% were aware that treatment was available, but only 22% understood that HCV could be cured. Of 418 who had heard of treatment, 86 (21%) reported an evaluation by a provider that included a discussion of treatment of whom 30 refused treatment, 20 deferred and 36 reported initiating treatment (6% overall). The most common reasons for refusal were related to treatment-related perceptions and a low perceived need of treatment. Compared to those who had discussed treatment with their provider, those who had not were more likely to be injecting drugs, less likely to have health insurance, and less knowledgeable about treatment. Low HCV treatment effectiveness was observed in this IDU population. Comprehensive integrated care strategies that incorporate education, case-management and peer support are needed to improve care and treatment of HCV-infected IDUs. PMID:18165889

  5. [Drug delivery strategies for targeted treatment of inflammatory bowel disease].

    PubMed

    Lautenschläger, C; Schmidt, C; Lange, K; Stallmach, A

    2015-03-01

    Inflammatory bowel disease (IBD) is a frequently occurring disease in young people, which is characterized by chronic inflammation of the gastrointestinal tract. The therapy of IBD is dominated by the administration of anti-inflammatory and immunosuppressive agents, which suppress the intestinal inflammatory burden and improve the disease-related symptoms. Present treatment strategies are characterized by a limited therapeutical efficacy and the occurrence of adverse drug reactions. The development of novel disease-targeted drug delivery strategies is preferable for a more effective therapy and thus demonstrates the potential to address unmet medical needs. This review gives an overview about drug delivery strategies for the treatment of IBD. Therefore, established intestine-targeting strategies for a selective drug release into the diseased part of the gastrointestinal tract will be presented, including prodrugs, and dosage forms with pH-/time-dependent drug release. Furthermore future-oriented disease-targeting strategies for a selective drug release into the intestinal inflammation will be described, including micro-/nanosized synthetic and biologic drug carriers. This novel therapeutic approach may enable a more effective anti-inflammatory treatment of IBD with reduced risks of adverse reactions. PMID:25723326

  6. Pharmacokinetic strategies for treatment of drug overdose and addiction

    PubMed Central

    Gorelick, David A

    2012-01-01

    The pharmacokinetic treatment strategy targets the drug molecule itself, aiming to reduce drug concentration at the site of action, thereby minimizing any pharmacodynamic effect. This approach might be useful in the treatment of acute drug toxicity/overdose and in the long-term treatment of addiction. Phase IIa controlled clinical trials with anticocaine and antinicotine vaccines have shown good tolerability and some efficacy, but Phase IIb and III trials have been disappointing because of the failure to generate adequate antibody titers in most participants. Monoclonal antibodies against cocaine, methamphetamine and phencyclidine have shown promise in animal studies, as has enhancing cocaine metabolism with genetic variants of human butyrylcholinesterase, with a bacterial esterase, and with catalytic monoclonal antibodies. Pharmacokinetic treatments offer potential advantages in terms of patient adherence, absence of medication interactions and benefit for patients who cannot take standard medications. PMID:22300100

  7. Recent advancement of gelatin nanoparticles in drug and vaccine delivery.

    PubMed

    Sahoo, Nityananda; Sahoo, Ranjan Ku; Biswas, Nikhil; Guha, Arijit; Kuotsu, Ketousetuo

    2015-11-01

    Novel drug delivery system using nanoscale materials with a broad spectrum of applications provides a new therapeutic foundation for technological integration and innovation. Nanoparticles are suitable drug carrier for various routes of administration as well as rapid recognition by the immune system. Gelatin, the biological macromolecule is a versatile drug/vaccine delivery carrier in pharmaceutical field due to its biodegradable, biocompatible, non-antigenicity and low cost with easy availability. The surface of gelatin nanoparticles can be modified with site-specific ligands, cationized with amine derivatives or, coated with polyethyl glycols to achieve targeted and sustained release drug delivery. Compared to other colloidal carriers, gelatin nanoparticles are better stable in biological fluids to provide the desired controlled and sustained release of entrapped drug molecules. The current review highlights the different formulation aspects of gelatin nanoparticles which affect the particle characteristics like zeta potential, polydispersity index, entrapment efficacy and drug release properties. It has also given emphasis on the major applications of gelatin nanoparticles in drug and vaccine delivery, gene delivery to target tissues and nutraceutical delivery for improving the poor bioavailabity of bioactive phytonutrients.

  8. ADVANCED TOOLS FOR ASSESSING SELECTED PRESCRIPTION AND ILLICIT DRUGS IN TREATED SEWAGE EFFLUENTS AND SOURCE WATERS

    EPA Science Inventory

    The purpose of this poster is to present the application and assessment of advanced technologies in a real-world environment - wastewater effluent and source waters - for detecting six drugs (azithromycin, fluoxetine, omeprazole, levothyroxine, methamphetamine, and methylenedioxy...

  9. Recent Advances in Hydrocortisone Replacement Treatment.

    PubMed

    Mallappa, Ashwini; Debono, Miguel

    2016-01-01

    Since the first use of cortisone in patients around 65 years ago, the use of synthetic glucocorticoids has made a crucial impact on the treatment of several diseases in medicine. Although significant reductions in morbidity and mortality have occurred in patients suffering from cortisol deficiency, conventional hydrocortisone replacement treatment is still inadequate. A major limitation is that it fails to replace cortisol in a physiological manner. Cortisol has a distinct circadian rhythm and acts as a secondary messenger synchronizing the central to peripheral clocks, hence playing a key role in biological processes and the circadian timing system. Circadian misalignment has been associated with ill-health and so nonphysiological glucocorticoid treatment could explain the increased mortality rate, poor quality of life and metabolic complications in patients suffering from adrenal insufficiency. Attempts at replacing cortisol in a physiological manner have shown significant progress in the past decade with the development of modified-release formulations of hydrocortisone (Chronocort® and Plenadren®) and continuous subcutaneous hydrocortisone infusions. Initial studies investigating the use of these replacement regimens are promising, demonstrating both clinical and biochemical improvement. Larger studies are needed to determine whether this novel approach enhances long-term outcomes in both children and adults with cortisol deficiency. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. Published by S. Karger AG, Basel.

  10. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2013.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2014-02-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2013. Studies on food allergy suggest that (1) 7.6% of the US population is affected, (2) a "healthy" early diet might prevent food allergy, (3) the skin might be an important route of sensitization, (4) allergen component testing might aid diagnosis, (5) the prognosis of milk allergy might be predictable through early testing, (6) oral or sublingual immunotherapy show promise but also have caveats, and (7) preclinical studies show promising alternative modes of immunotherapy and desensitization. Studies on eosinophilic esophagitis show a relationship to connective tissue disorders and that dietary management is an effective treatment for adults. Markers of anaphylaxis severity have been determined and might inform potential diagnostics and therapeutic targets. Insights on serum tests for drug and insect sting allergy might result in improved diagnostics. Genetic and immune-mediated defects in skin epithelial differentiation contribute to the severity of atopic dermatitis. Novel management approaches to treatment of chronic urticaria, including use of omalizumab, are being identified.

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

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2012-01-01

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

  12. Drug treatment of hypertensive crisis in children.

    PubMed

    Thomas, Christopher A

    2011-10-01

    Hypertensive crisis is a relatively rare event and is associated with significant morbidity and mortality in adults and pediatric patients alike. Rapid, safe, and effective treatment is imperative to alleviate immediate presenting clinical symptoms, prevent devastating morbidity, preserve long-term quality of life, and prevent mortality. Many medications in the hypertensive crisis arsenal have been used for nearly half a century. Nearly all treatment options have been utilized in children for decades, yet reliable data and sound clinical literature remain elusive. Every agent considered to be a first-line, second-line, or adjunctive option has yet to be evaluated in a randomized controlled trial in pediatric patients. With a paucity of clinical data to form evidence-based decisions, the clinician must rely entirely on the extrapolation from adult data and small retrospective studies, case series, and case reports of medication use in pediatric patients. Although more research in the treatment of pediatric hypertensive crisis is desperately needed, current practice demands a sharp knowledge of the pediatric clinical literature and pharmacology in this area as an essential tool to consistently improve patient outcomes with respect to morbidity and mortality.

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

    PubMed

    Wang, F; Fan, Q X

    2016-09-23

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

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

    PubMed

    Wang, F; Fan, Q X

    2016-09-23

    Esophageal cancer (EC) is one of common malignant tumors, and the incidence and mortality of EC in China rank the first place in the world. Because of the occult onset, the early atypical symptoms, and the lack of effective early diagnostic methods, most of patients are diagnosed at an advanced stage of the disease and lost the chance of surgery. Comprehensive treatment including palliative medical treatment, molecular targeted therapy, immunotherapy and so on is appropriate for these patients. How to choose the chemotherapy regimen and formulate reasonable treatment plan has become a hot spot in clinical research. Molecular targeted drugs have become a new developmental direction in cancer treatment because of their high specificity and antitumor activity, but the effects on esophageal cancer remain controversial. With the development of immune check point blockade treatment, breakthrough has been made in tumor immunotherapy, which has become an important means in cancer comprehensive treatment and shown a good prospect of treatment. PMID:27647396

  15. Advances in the use of nanocarriers for cancer diagnosis and treatment

    PubMed Central

    Vieira, Débora Braga; Gamarra, Lionel Fernel

    2016-01-01

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

  16. Recent advances in liposome surface modification for oral drug delivery.

    PubMed

    Nguyen, Thanh Xuan; Huang, Lin; Gauthier, Mario; Yang, Guang; Wang, Qun

    2016-05-01

    Oral delivery via the gastrointestinal (GI) tract is the dominant route for drug administration. Orally delivered liposomal carriers can enhance drug solubility and protect the encapsulated theraputic agents from the extreme conditions found in the GI tract. Liposomes, with their fluid lipid bilayer membrane and their nanoscale size, can significantly improve oral absorption. Unfortunately, the clinical applications of conventional liposomes have been hindered due to their poor stability and availability under the harsh conditions typically presented in the GI tract. To overcome this problem, the surface modification of liposomes has been investigated. Although liposome surface modification has been extensively studied for oral drug delivery, no review exists so far that adequately covers this topic. The purpose of this paper is to summarize and critically analyze emerging trends in liposome surface modification for oral drug delivery. PMID:27074098

  17. Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection.

    PubMed

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

    2014-08-01

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

  18. Antiepileptic drug treatment strategies in neonatal epilepsy.

    PubMed

    Hernan, A E; Holmes, G L

    2016-01-01

    The highest risk of seizures across the lifespan is in the neonatal period. The enhanced excitability of the immature brain compared to the mature brain is related to the sequential development and expression of essential neurotransmitter signaling pathways. During the neonatal period there is an overabundance of excitatory receptors, and γ-amino-butyric acid (GABA) is potentially depolarizing, as opposed to hyperpolarizing in the older brain. While this enhanced excitability is required for regulation of activity-dependent synapse formation and refining of synaptic connections that are necessary for normal brain development, enhanced excitability predisposes the immature brain to seizures. In addition to being common, neonatal seizures are very difficult to treat; antiepileptic drugs used in older children and adults are less efficacious, and possibly detrimental to brain development. In an effort to target the unique features of neurotransmission in the neonate, bumetanide, an NKCC1 inhibitor which reduces intraneuronal Cl(-) and induces a significant shift of EGABA toward more hyperpolarized values in vitro, has been used to treat neonatal seizures. As the understanding of the pathophysiology of genetic forms of neonatal epilepsy has evolved there have been a few successful attempts to pharmacologically target the mutated protein. This approach, while promising, is challenging due to the findings that the genetic syndromes presenting in infancy demonstrate genetic heterogeneity in regard to both the mutated gene and its function. PMID:27323943

  19. The treatment of advanced juvenile nasopharyngeal angiofibroma.

    PubMed

    McGahan, R A; Durrance, F Y; Parke, R B; Easley, J D; Chou, J L

    1989-11-01

    Fifteen patients with juvenile nasopharyngeal angiofibroma (JNA) were treated in the Department of Radiation Oncology, Baylor College of Medicine between 1973 and 1986. All patients underwent radiographic evaluation including CT scanning, selective digital subtraction angiography, tomograms, or MRI. Patients referred for definitive irradiation exhibited extensive tumor involvement. Eleven of 15 patients had middle cranial fossa involvement; cavernous sinus extension was observed in six patients. Ten patients were treated with primary radiation therapy; five patients had surgical resection initially and were referred for radiation therapy upon local recurrence. Follow-up ranges from 1 1/2-13 years. Four of the 5 patients who received 3200 cGy in 200 cGy fractions demonstrated tumor recurrence within 2 years after irradiation. All recurrences were ultimately controlled by either further irradiation and/or resection. No tumor recurrence was encountered among the patients treated at the higher tumor doses (36-46 Gy). No severe complications have been observed. Radiation therapy utilizing carefully tailored fields is an appropriate therapeutic approach to patients with extensive disease or intracranial extension. A total dose of greater than 40 Gy may allow improved local control for advanced lesions.

  20. Use of therapeutic touch in treatment of drug addictions.

    PubMed

    Hagemaster, J

    2000-04-01

    The purpose of this pilot study is to examine the efficacy of Therapeutic Touch (TT) as a form of treatment intervention with persons who abuse alcohol and/or other drugs. A between-subjects design compared treatment outcomes of three groups of alcohol and other drug abusers over five months. The Addiction Severity Index (ASI), Michigan Alcoholism Screening Test (MAST), Beck Depression Inventory (BI), and Personal Experiences: Therapeutic Touch and Frequency of Alcohol/Drug Use questionnaires were administered to the group receiving TT (Group A) and both control groups (Mimic TT Group B and No Intervention Group C) at various points in the study. Preliminary findings indicate that the use of TT could be effective in prolonging periods of abstinence for alcohol and other drug abusers.

  1. Nanostructured lipid carriers system: recent advances in drug delivery.

    PubMed

    Iqbal, Md Asif; Md, Shadab; Sahni, Jasjeet Kaur; Baboota, Sanjula; Dang, Shweta; Ali, Javed

    2012-12-01

    Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier. PMID:22931500

  2. Advances in Tourette syndrome: diagnoses and treatment.

    PubMed

    Serajee, Fatema J; Mahbubul Huq, A H M

    2015-06-01

    Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder characterized by multiple motor tics and at least one vocal or phonic tic, and often one or more comorbid psychiatric disorders. Premonitory sensory urges before tic execution and desire for "just-right" perception are central features. The pathophysiology involves cortico-striato-thalamo-cortical circuits and possibly dopaminergic system. TS is considered a genetic disorder but the genetics is complex and likely involves rare mutations, common variants, and environmental and epigenetic factors. Treatment is multimodal and includes education and reassurance, behavioral interventions, pharmacologic, and rarely, surgical interventions. PMID:26022170

  3. Advances in Tourette syndrome: diagnoses and treatment.

    PubMed

    Serajee, Fatema J; Mahbubul Huq, A H M

    2015-06-01

    Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder characterized by multiple motor tics and at least one vocal or phonic tic, and often one or more comorbid psychiatric disorders. Premonitory sensory urges before tic execution and desire for "just-right" perception are central features. The pathophysiology involves cortico-striato-thalamo-cortical circuits and possibly dopaminergic system. TS is considered a genetic disorder but the genetics is complex and likely involves rare mutations, common variants, and environmental and epigenetic factors. Treatment is multimodal and includes education and reassurance, behavioral interventions, pharmacologic, and rarely, surgical interventions.

  4. Advances in Personalized Targeted Treatment of Metastatic Melanoma and Non-Invasive Tumor Monitoring

    PubMed Central

    Klinac, Dragana; Gray, Elin S.; Millward, Michael; Ziman, Mel

    2013-01-01

    Despite extensive scientific progress in the melanoma field, treatment of advanced stage melanoma with chemotherapeutics and biotherapeutics has rarely provided response rates higher than 20%. In the past decade, targeted inhibitors have been developed for metastatic melanoma, leading to the advent of more personalized therapies of genetically characterized tumors. Here we review current melanoma treatments and emerging targeted molecular therapies. In particular we discuss the mutant BRAF inhibitors Vemurafenib and Dabrafenib, which markedly inhibit tumor growth and advance patients’ overall survival. However this response is almost inevitably followed by complete tumor relapse due to drug resistance hampering the encouraging initial responses. Several mechanisms of resistance within and outside the MAPK pathway have now been uncovered and have paved the way for clinical trials of combination therapies to try and overcome tumor relapse. It is apparent that personalized treatment management will be required in this new era of targeted treatment. Circulating tumor cells (CTCs) provide an easily accessible means of monitoring patient relapse and several new approaches are available for the molecular characterization of CTCs. Thus CTCs provide a monitoring tool to evaluate treatment efficacy and early detection of drug resistance in real time. We detail here how advances in the molecular analysis of CTCs may provide insight into new avenues of approaching therapeutic options that would benefit personalized melanoma management. PMID:23515890

  5. Incorporating Stage-Specific Drug Action into Pharmacological Modeling of Antimalarial Drug Treatment

    PubMed Central

    2016-01-01

    Pharmacological modeling of antiparasitic treatment based on a drug's pharmacokinetic and pharmacodynamic properties plays an increasingly important role in identifying optimal drug dosing regimens and predicting their potential impact on control and elimination programs. Conventional modeling of treatment relies on methods that do not distinguish between parasites at different developmental stages. This is problematic for malaria parasites, as their sensitivity to drugs varies substantially during their 48-h developmental cycle. We investigated four drug types (short or long half-lives with or without stage-specific killing) to quantify the accuracy of the standard methodology. The treatment dynamics of three drug types were well characterized with standard modeling. The exception were short-half-life drugs with stage-specific killing (i.e., artemisinins) because, depending on time of treatment, parasites might be in highly drug-sensitive stages or in much less sensitive stages. We describe how to bring such drugs into pharmacological modeling by including additional variation into the drug's maximal killing rate. Finally, we show that artemisinin kill rates may have been substantially overestimated in previous modeling studies because (i) the parasite reduction ratio (PRR) (generally estimated to be 104) is based on observed changes in circulating parasite numbers, which generally overestimate the “true” PRR, which should include both circulating and sequestered parasites, and (ii) the third dose of artemisinin at 48 h targets exactly those stages initially hit at time zero, so it is incorrect to extrapolate the PRR measured over 48 h to predict the impact of doses at 48 h and later. PMID:26902760

  6. Recent advances in treatment for Benign Prostatic Hyperplasia.

    PubMed

    van Rij, Simon; Gilling, Peter

    2015-01-01

    Clinical benign prostatic hyperplasia (BPH), often identified as a worsening ability of a male to pass urine, is a significant problem for men in our society. In 2015, the use of personalised medicine is tailoring treatment to individual patient needs and to genetic characteristics. Technological advances in surgical treatment are changing the way BPH is treated and are resulting in less morbidity. The future of BPH treatments is exciting, and a number of novel techniques are currently under clinical trial.

  7. Recent advances in treatment for Benign Prostatic Hyperplasia.

    PubMed

    van Rij, Simon; Gilling, Peter

    2015-01-01

    Clinical benign prostatic hyperplasia (BPH), often identified as a worsening ability of a male to pass urine, is a significant problem for men in our society. In 2015, the use of personalised medicine is tailoring treatment to individual patient needs and to genetic characteristics. Technological advances in surgical treatment are changing the way BPH is treated and are resulting in less morbidity. The future of BPH treatments is exciting, and a number of novel techniques are currently under clinical trial. PMID:26918132

  8. Recent advances in treatment for Benign Prostatic Hyperplasia

    PubMed Central

    van Rij, Simon; Gilling, Peter

    2015-01-01

    Clinical benign prostatic hyperplasia (BPH), often identified as a worsening ability of a male to pass urine, is a significant problem for men in our society. In 2015, the use of personalised medicine is tailoring treatment to individual patient needs and to genetic characteristics. Technological advances in surgical treatment are changing the way BPH is treated and are resulting in less morbidity. The future of BPH treatments is exciting, and a number of novel techniques are currently under clinical trial. PMID:26918132

  9. The treatment of chronic pain with psychotropic drugs

    PubMed Central

    Merskey, H.; Hester, R. A.

    1972-01-01

    The treatment is described of thirty patients with chronic nervous system lesion causing intractable pain. Moderately good relief of pain was obtained with a combination of phenothiazines (especially pericyazine), antidepressant drugs and antihistamines. The theoretical implications of this are discussed and it is suggested that the drugs in question act partly by virtue of an effect on the multisynaptic neuronal systems whose activities are related to the experience of pain. PMID:4404064

  10. Drugs in induction and treatment of idiopathic inflammatory myopathies.

    PubMed

    Iaccarino, Luca; Bartoloni, Elena; Gerli, Roberto; Alunno, Alessia; Barsotti, Simone; Cafaro, Giacomo; Gatto, Mariele; Talarico, Rosaria; Tripoli, Alessandra; Zen, Margherita; Neri, Rossella; Doria, Andrea

    2014-12-01

    Idiopathic inflammatory myopathies (IIM) are a rare disease; so far standardized therapy has not been adequately defined by national or international guidelines or recommendations. Corticosteroids are the mainstay of treatment, but these drugs are burdened by several side effects. Thus, additional treatment based on immunosuppressive agents, especially azathioprine, methotrexate, mycophenolate mofetil and cyclosporine, is often needed. This combinate approach both improves the disease response and allows reduction of the dosage of corticosteroids, decreasing the risk of steroid-related long-term complications. Biological agents, particularly B cell depleting agent, are emergent therapeutic tools for refractory cases. Notably, drugs currently used for the therapy of IIM or other rheumatologic and non-rheumatologic conditions can induce myopathy. Drug-induced myopathies represent a considerable part of the complex topic of muscular disorders and should be always considered in the usual diagnostic work-up of a subject with muscle disease. Several mechanisms have been advocated to explain muscular damage induced by a number of drugs and, although a recovery after drug removal is usually observed, severe or persistent myopathy may be observed following the administration of some drugs, particularly in subjects with genetic predisposition. In this review the traditional and novel therapeutic approaches for patients with IIM, particularly biologics, will be discussed and an overview on drug-induced myopathies will also be provided. PMID:26000161

  11. Illicit drug use and treatment in South Africa: a review.

    PubMed

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

    2010-11-01

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

  12. [Advances in the treatment of secondary osteoporosis].

    PubMed

    Galindo Zavala, R; Núñez Cuadros, E; Díaz Cordovés-Rego, G; Urda Cardona, A L

    2014-12-01

    Osteoporosis is being increasingly recognised in paediatric practice as a consequence of the increasing life expectancy of children who suffer from chronic diseases and other factors. There are many non-pharmacological measures that can improve children' bone health, for example, avoiding inflammatory activity and osteotoxic treatments; increasing sun exposure and weight-bearing exercise, and maintaining an adequate nutritional status. Vitamin D and calcium supplements have been proposed as a measure to increase bone mass, but their effect and therapeutic indications are not completely clear. On the other hand, bisphosphonates are currently the only pharmacological alternative for the patients with infantile secondary osteoporosis. However, more studies are required on the therapeutic indications, posology, and long term secondary effects of biphosphonates. The aim of this article is to analyze the scientific evidence of the effectiveness of the therapeutic alternatives for childhood secondary osteoporosis and their safety in children. PMID:25441207

  13. [Advances in the treatment of secondary osteoporosis].

    PubMed

    Galindo Zavala, R; Núñez Cuadros, E; Díaz Cordovés-Rego, G; Urda Cardona, A L

    2014-12-01

    Osteoporosis is being increasingly recognised in paediatric practice as a consequence of the increasing life expectancy of children who suffer from chronic diseases and other factors. There are many non-pharmacological measures that can improve children' bone health, for example, avoiding inflammatory activity and osteotoxic treatments; increasing sun exposure and weight-bearing exercise, and maintaining an adequate nutritional status. Vitamin D and calcium supplements have been proposed as a measure to increase bone mass, but their effect and therapeutic indications are not completely clear. On the other hand, bisphosphonates are currently the only pharmacological alternative for the patients with infantile secondary osteoporosis. However, more studies are required on the therapeutic indications, posology, and long term secondary effects of biphosphonates. The aim of this article is to analyze the scientific evidence of the effectiveness of the therapeutic alternatives for childhood secondary osteoporosis and their safety in children.

  14. Development of treatment strategies for advanced neuroblastoma.

    PubMed

    Hara, Junichi

    2012-06-01

    Neuroblastoma is the most common cancer in childhood. The majority of patients with neuroblastoma are assigned to the high-risk group based on age at diagnosis, stage, histology, MYCN status, and DNA ploidy. Their prognosis remains unsatisfactory; the 5-year event-free survival (EFS) rate is generally 40 %. During the past 20 years, much effort has been made to reinforce chemotherapy, including the introduction of high-dose chemotherapy with autologous stem cell rescue, resulting in a 5-year EFS rate of around 30 %. Subsequently, maintenance therapy aimed at eradicating residual tumors after induction and consolidation therapies was introduced, consisting of differentiation-inducing agents, retinoids, and immunotherapy using anti-GD2 antibodies combined with cytokines. However, such additional treatment provided benefit to only 10-20 % of patients, while the prognosis of about half the patients remains poor. Currently, novel targeted agents are under development. Among them, anaplastic lymphoma kinase (ALK) inhibitors and aurora kinase A inhibitors are promising. ALK somatic mutation or gene amplification predisposing neuroblastoma development occurs in up to 15 % of neuroblastomas. Crizotinib is a dual-specific inhibitor of ALK/Met and inhibits proliferation of neuroblastoma cells harboring R1275Q-mutated ALK or amplified wild-type ALK, but not cells harboring F1174L. Instead, cells with F1174L are sensitive to another small molecule ALK inhibitor, TAE684. Aurora kinase A plays a pivotal role in centrosome maturation and spindle formation during mitosis. MLN8237 (alisertib) is a small molecule inhibitor of aurora kinase A that is currently in early-phase clinical testing. Future treatment will be individually planned, adapting targeted agents based on personal biological tumor characteristics.

  15. Why Do We Need New Drug Classes for HIV Treatment and Prevention?

    PubMed

    Waheed, Abdul A; Tachedjian, Gilda

    2016-01-01

    The biomedical intervention that has had a major impact on the natural history of HIV and on the global HIV epidemic is antiretroviral therapy (ART). However, the emergence of drug-resistant HIV, an inevitable consequence of increasing use of antiretroviral drugs, poses a major threat to ART success. At the turn of this century, access to life-saving ART was accelerated in low and middle-income countries with the Millennium Development Goal of 15 million individuals receiving ART by 2015 expected to be achieved. However, ART access needs to continue to expand to help bring HIV under control by 2030. The standard of care for people living with HIV in resource- limited settings differs dramatically compared to high-income countries, and not unexpectedly, ART rollout in these settings has resulted in an increase in acquired and transmitted drug resistance. Also of concern, the same drug classes used for ART have been approved or are being progressed for HIV prevention and drug resistance could mitigate their effectiveness for treatment and prevention. In the absence of an effective HIV vaccine and cure, it is imperative that the antiretroviral drug pipeline contains new classes of HIV inhibitors that are active against circulating drug-resistant strains. Studies to advance our fundamental understanding of HIV replication needs to continue, including the interplay between virus and host cell factors, to identify and characterize new drug targets for chemotherapeutic intervention.

  16. 28 CFR 550.53 - Residential Drug Abuse Treatment Program (RDAP).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  17. 28 CFR 550.53 - Residential Drug Abuse Treatment Program (RDAP).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  18. 28 CFR 550.53 - Residential Drug Abuse Treatment Program (RDAP).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  19. 28 CFR 550.53 - Residential Drug Abuse Treatment Program (RDAP).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  20. 21 CFR 316.40 - Treatment use of a designated orphan drug.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Treatment use of a designated orphan drug. 316.40... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Open Protocols for Investigations § 316.40 Treatment use of a designated orphan drug. Prospective investigators seeking to obtain treatment use of designated orphan...

  1. Treatment of drug abusers in Malaysia: a comparison.

    PubMed

    Johnson, S H

    1983-10-01

    The purpose of this paper is to compare two forms of treatment for heroin abusers in Malaysia--traditional medicine and institutional--and to evaluate which form of treatment the drug abusers consider more effective. The study involved interviewing 100 male drug abusers in Malaysia who had had treatment from an institution and from a traditional healer. The data revealed that traditional medicine was better for some abusers, but institutional treatment was better for others, depending upon an individual's own needs and personality. Advantages and disadvantages of both forms of treatment were given by those interviewed. The data can be used as guidelines for the development of a more flexible, individualized program within an institutional setting in Malaysia. PMID:6642801

  2. Treatment of drug abusers in Malaysia: a comparison.

    PubMed

    Johnson, S H

    1983-10-01

    The purpose of this paper is to compare two forms of treatment for heroin abusers in Malaysia--traditional medicine and institutional--and to evaluate which form of treatment the drug abusers consider more effective. The study involved interviewing 100 male drug abusers in Malaysia who had had treatment from an institution and from a traditional healer. The data revealed that traditional medicine was better for some abusers, but institutional treatment was better for others, depending upon an individual's own needs and personality. Advantages and disadvantages of both forms of treatment were given by those interviewed. The data can be used as guidelines for the development of a more flexible, individualized program within an institutional setting in Malaysia.

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

    PubMed Central

    Kalepu, Sandeep; Nekkanti, Vijaykumar

    2015-01-01

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

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

    PubMed

    Kalepu, Sandeep; Nekkanti, Vijaykumar

    2015-09-01

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

  5. Strategies and Advancement in Antibody-Drug Conjugate Optimization for Targeted Cancer Therapeutics

    PubMed Central

    Kim, Eunhee G.; Kim, Kristine M.

    2015-01-01

    Antibody-drug conjugates utilize the antibody as a delivery vehicle for highly potent cytotoxic molecules with specificity for tumor-associated antigens for cancer therapy. Critical parameters that govern successful antibody-drug conjugate development for clinical use include the selection of the tumor target antigen, the antibody against the target, the cytotoxic molecule, the linker bridging the cytotoxic molecule and the antibody, and the conjugation chemistry used for the attachment of the cytotoxic molecule to the antibody. Advancements in these core antibody-drug conjugate technology are reflected by recent approval of Adectris® (anti-CD30-drug conjugate) and Kadcyla® (anti-HER2 drug conjugate). The potential approval of an anti-CD22 conjugate and promising new clinical data for anti-CD19 and anti-CD33 conjugates are additional advancements. Enrichment of antibody-drug conjugates with newly developed potent cytotoxic molecules and linkers are also in the pipeline for various tumor targets. However, the complexity of antibody-drug conjugate components, conjugation methods, and off-target toxicities still pose challenges for the strategic design of antibody-drug conjugates to achieve their fullest therapeutic potential. This review will discuss the emergence of clinical antibody-drug conjugates, current trends in optimization strategies, and recent study results for antibody-drug conjugates that have incorporated the latest optimization strategies. Future challenges and perspectives toward making antibody-drug conjugates more amendable for broader disease indications are also discussed. PMID:26535074

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

    ERIC Educational Resources Information Center

    Page, Richard C.; Mitchell, Sam

    1986-01-01

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

  7. Ion channel profiling to advance drug discovery and development.

    PubMed

    Zou, Beiyan

    2015-11-01

    In vitro pharmacological profiling provides crucial information to eliminate drug candidates with potential toxicity early in drug discovery and reduce failure in later stages. It has become a common practice in industry to test lead compounds against a panel of ion channel targets for selectivity and safety liability at early drug discovery stages. Ion channel profiling technologies include binding assays, flux assays, fluorescent membrane potential assays, automated and conventional electrophysiology. Instead of examining compound effects on individual ion channel targets, automated current clamp, optical electrophysiology, and multi-electrode assays have evolved to investigate the integrated compound effects on cardiac myocytes. This review aims to provide an overview of ion channel profiling for cardiac safety and comparisons of various technologies.

  8. Profile of olaparib in the treatment of advanced ovarian cancer

    PubMed Central

    Chase, Dana M; Patel, Shreya; Shields, Kristin

    2016-01-01

    Olaparib is a poly(ADP-ribose) polymerase inhibitor that received accelerated approval from the US Food and Drug Administration as monotherapy for patients with germline BRCA mutations and ovarian cancer treated with three or more prior lines of chemotherapy. This article summarizes the mechanism of poly(ADP-ribose) polymerase inhibition, therapeutic profile and uses of olaparib, and current and ongoing literature pertaining to olaparib in advanced ovarian cancer. PMID:27186080

  9. Cellulite: advances in treatment: facts and controversies.

    PubMed

    Emanuele, Enzo

    2013-01-01

    Cellulite is traditionally considered a highly prevalent aesthetic condition in women. From a clinical standpoint, it is characterized by a cottage-cheese-like appearance of the skin, which can be most commonly found in certain areas of the body (eg, thighs, buttocks, and legs). Although cellulite is generally asymptomatic, the more severe stages can be accompanied by the appearance of painful nodules and increased local temperature, which are suggestive of an inflammatory reaction occurring in the dermis and in the underlying subcutaneous adipose tissue. Whether cellulite is a real disease or only a disturbing aesthetic issue is still a matter of controversy. This debate notwithstanding, it seems clear from market trends that there is considerable commercial interest in developing effective strategies aimed at reducing the cottage-cheese-like appearance of cellulite areas. Quite disturbingly, the majority of treatment attempts to date have been conducted in an empirical manner and without the application of rigorous scientific methodology. This is likely due--at least in part--to the lack of major, evidence-based pathophysiological insights into the nature of this condition. More stringent regulatory control is needed over commercial products aiming at improving the appearance of cellulite.

  10. Combinations of Drugs in the Treatment of Obesity

    PubMed Central

    Halpern, Bruno; Oliveira, Eduardo S. L.; Faria, André M.; Halpern, Alfredo; de Melo, Maria Edna; Cercato, Cintia; Mancini, Marcio C.

    2010-01-01

    Obesity is a chronic disease associated with excess morbidity and mortality. Clinical treatment, however, currently offers disappointing results, with very high rates of weight loss failure or weight regain cycles, and only two drugs (orlistat and sibutramine) approved for long-term use. Drugs combinations can be an option for its treatment but, although widely used in clinical practice, very few data are available in literature for its validation. Our review focuses on the rationale for their use, with advantages and disadvantages; on combinations often used, with or without studies; and on new perspectives of combinations being studied mainly by the pharmaceutical industry.

  11. Recent Advances in Drug Discovery from South African Marine Invertebrates.

    PubMed

    Davies-Coleman, Michael T; Veale, Clinton G L

    2015-10-01

    Recent developments in marine drug discovery from three South African marine invertebrates, the tube worm Cephalodiscus gilchristi, the ascidian Lissoclinum sp. and the sponge Topsentia pachastrelloides, are presented. Recent reports of the bioactivity and synthesis of the anti-cancer secondary metabolites cephalostatin and mandelalides (from C. gilchristi and Lissoclinum sp., respectively) and various analogues are presented. The threat of drug-resistant pathogens, e.g., methicillin-resistant Staphylococcus aureus (MRSA), is assuming greater global significance, and medicinal chemistry strategies to exploit the potent MRSA PK inhibition, first revealed by two marine secondary metabolites, cis-3,4-dihydrohamacanthin B and bromodeoxytopsentin from T. pachastrelloides, are compared. PMID:26473891

  12. Recent Advances in Drug Discovery from South African Marine Invertebrates

    PubMed Central

    Davies-Coleman, Michael T.; Veale, Clinton G. L.

    2015-01-01

    Recent developments in marine drug discovery from three South African marine invertebrates, the tube worm Cephalodiscus gilchristi, the ascidian Lissoclinum sp. and the sponge Topsentia pachastrelloides, are presented. Recent reports of the bioactivity and synthesis of the anti-cancer secondary metabolites cephalostatin and mandelalides (from C. gilchristi and Lissoclinum sp., respectively) and various analogues are presented. The threat of drug-resistant pathogens, e.g., methicillin-resistant Staphylococcus aureus (MRSA), is assuming greater global significance, and medicinal chemistry strategies to exploit the potent MRSA PK inhibition, first revealed by two marine secondary metabolites, cis-3,4-dihydrohamacanthin B and bromodeoxytopsentin from T. pachastrelloides, are compared. PMID:26473891

  13. From club drug to orphan drug: sodium oxybate (Xyrem) for the treatment of cataplexy.

    PubMed

    Fuller, David E; Hornfeldt, Carl S

    2003-09-01

    Narcolepsy, a rare disease with a prevalence of 0.05% in the general population, affects an estimated 140,000 patients in the United States. Patients have been able to lead fuller personal and professional lives since the Food and Drug Administration approved sodium oxybate (Xyrem) in 2002 for treatment of cataplexy in patients with narcolepsy. Previously, gamma-hydroxybutyrate (GHB), the active ingredient of sodium oxybate, had been a substance of abuse, most notoriously as a date-rape drug. Public Law 106-172, the date-rape prohibition act enacted in 2000, was modified to allow the drug to be legally administered for medical purposes. Because of the apprehension regarding the risk of possible drug diversion after the approval of sodium oxybate and concerns about safety, the Xyrem Risk Management Program was created. This program has been successful in satisfying the needs of patients and physicians while ensuring responsible distribution of the drug.

  14. From club drug to orphan drug: sodium oxybate (Xyrem) for the treatment of cataplexy.

    PubMed

    Fuller, David E; Hornfeldt, Carl S

    2003-09-01

    Narcolepsy, a rare disease with a prevalence of 0.05% in the general population, affects an estimated 140,000 patients in the United States. Patients have been able to lead fuller personal and professional lives since the Food and Drug Administration approved sodium oxybate (Xyrem) in 2002 for treatment of cataplexy in patients with narcolepsy. Previously, gamma-hydroxybutyrate (GHB), the active ingredient of sodium oxybate, had been a substance of abuse, most notoriously as a date-rape drug. Public Law 106-172, the date-rape prohibition act enacted in 2000, was modified to allow the drug to be legally administered for medical purposes. Because of the apprehension regarding the risk of possible drug diversion after the approval of sodium oxybate and concerns about safety, the Xyrem Risk Management Program was created. This program has been successful in satisfying the needs of patients and physicians while ensuring responsible distribution of the drug. PMID:14524654

  15. First-Line Treatment for Tuberculosis (TB), Drug Resistant TB -- A Visual Tour

    MedlinePlus

    ... Skip Content Marketing Share this: Main Content Area Tuberculosis Drugs First-Line Treatment of TB for Drug- ... ago. See how these drugs work . Multidrug-Resistant Tuberculosis (MDR TB) and Second-Line Treatments MDR TB ...

  16. Effects of political conflict-induced treatment interruptions on HIV drug resistance.

    PubMed

    Mann, Marita; Lurie, Mark N; Kimaiyo, Sylvester; Kantor, Rami

    2013-01-01

    Thirty-four million people worldwide were living with the HIV by the end of 2010. Despite significant advances in antiretroviral therapy, drug resistance remains a major deterrent to successful, enduring treatment. Unplanned interruptions in antiretroviral therapy have negative effects on HIV treatment outcomes, including increased morbidity and mortality, as well as development of drug resistance. Treatment interruptions due to political conflicts, not infrequent in resource-limited settings, result in disruptions in health care, infrastructure, or treatment facilities and patient displacement. Such circumstances are ideal bases for antiretroviral therapy resistance development, but there is limited awareness of and data available on the association between political conflict and the development of HIV drug resistance. In this review we identify and discuss this association and review how varying antiretroviral therapy half-lives, genetic barriers, different HIV subtypes, and archived resistance can lead to lack of medication effectiveness upon post-conflict resumption of care. Optimized antiretroviral therapy stopping strategies as well as infrastructural concerns and stable HIV treatment systems to ensure continuity of care and rapid resumption of care must be addressed in order to mitigate risks of HIV drug resistance development during and after political conflicts. Increased awareness of such associations by clinicians as well as politicians and stakeholders is essential.

  17. Advances in the treatment of relapsing-remitting multiple sclerosis.

    PubMed

    Tanasescu, Radu; Ionete, Carolina; Chou, I-Jun; Constantinescu, Cris S

    2014-01-01

    This article reviews and discusses the approved and emerging therapies for multiple sclerosis (MS). MS is a chronic and disabling immune-mediated disease of the central nervous system (CNS) that affects mainly young adults. MS imposes a huge economic burden on healthcare systems and the society. Although the last 20 years have brought a continuous expansion in therapeutic options, there are still unmet needs in MS management. Available MS drugs have varying degrees of efficacy in reducing relapse risk. The long-term term effects of these treatments are incompletely known. New therapies, along with variations of currently available treatments, may prove more effective and tolerable than the available drugs. Treatments for MS differ with respect to the mode of administration, tolerability and likelihood of treatment adherence, side effects, and risk of major toxicity. The armamentarium of approved disease-modifying therapies in MS and those in development include: (1) the first approved, moderately effective, injectable interferon-β and glatiramer acetate; (2) oral drugs (fingolimod, laquinimod, teriflunomide, dimethyl fumarate); (3) monoclonal antibodies (rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab); and (4) immunosuppressive agents (e.g. mitoxantrone). The place of each drug in the therapeutic algorithm is dependent on its specific risk-benefit profile. Patients' clinical and paraclinical phenotypes and biomarker profile may help to elucidate disease subtypes and response to therapy in the future, thus allowing treatment individualization. PMID:24732658

  18. Posttreatment victimization and violence among adolescents following residential drug treatment.

    PubMed

    Hawke, Josephine M; Jainchill, Nancy; De Leon, George

    2003-02-01

    This article examines the relationships among experiences of childhood abuse, psychiatric disorders, self-reported victimization, and violent behavior, with a focus on gender differences. Data were obtained from treatment entry and 5-year post-treatment interviews of 446 adolescent clients in therapeutic community (TC) drug treatment programs throughout the United States and Canada. Fifty-eight percent of the sample indicated that they engaged in serious violent behaviors (e.g., beatings, threatening or using weapons against other people, or violent crimes such as assaults, rapes, murders) in the 5 years following their separation from TC treatment. Multivariate logistic regression analyses revealed that victimization in the posttreatment period was the most significant factor associated with violent behavior, and pretreatment childhood abuse experiences and psychiatric disorders were not significantly related to the odds of violent behavior. There were significant gender differences in self-reported victimization and violent behavior. The findings suggest that violence in young adulthood for males is related to increasing involvement in violent lifestyles that include drug trafficking, while violence among females is associated with the social and psychological consequences of drug involvement and victimization. High rates of violent involvement and victimization among former adolescent clients suggests the utility of incorporating interventions such as safety-oriented strategies for females or interventions that address involvement in the drug use lifestyles (i.e., use and dealing) for both males and females into residential treatment to reduce the likelihood of future violence. PMID:12568505

  19. Recent advances in the treatment of colon cancer.

    PubMed

    Xu, R; Zhou, B; Fung, P C W; Li, X

    2006-08-01

    Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Although surgical resection is still the only treatment capable of curing colon cancer, adjuvant therapy continues to play an important role in preventing recurrence and metastasis. In recent years remarkable progress has been made in the treatment of colon cancer. This review discusses recent advances in adjuvant therapy for colon cancer, including chemotherapy, immunotherapy, antiangiogenic therapy and apoptosis induction. In the meantime, molecular therapy is also elucidated in the above methods. All these new advances will provide new promises for patients of colon cancer. PMID:16691539

  20. China's new drug R&D is steadily advancing.

    PubMed

    Xu, W F

    2007-08-01

    China appears to consistently lag behind developed countries like the US, Japan, and the nations of Europe in the development of pharmaceuticals, putting China in an embarrassing situation. In fact, China is still dependent on foreign imports for most highly effective cures to major diseases such as cancer, diabetes, hepatitis, and neurodegenerative disease. There is no denying the fact that governmental support, and especially a signifi cant amount of fi nancial support and political assistance to include government restructuring, is needed for the establishment of new drug Research and Development (R&D). Fortunately, China's authorities have recently recognized the importance of new drug development and have committed to implementing strong measures to help establish new drug R&D. This improvement in the government's status is showing immediate and substantial promise in the field of pharmaceuticals. On January 4, 2007, a research group directed by Wang Ming-Wei, Head of the National Center for Drug Screening, Shanghai Institute of Materia Medica (SIMM), made a breakthrough in the development of novel category I anti-diabetes drugs with the support of the Ministry of Science & Technology of China, the National Natural Science Foundation (NSFC) of China, and the Shanghai municipal government. Taking almost four years, the group finally developed a nonpeptide agonist of small molecule glucagon-like peptide 1 receptors with effi cacy in diabetic db/db mice (Proc Natl Acad Sci U S A 2007;104:943-948). As an antidiabetes drug, a peptide hormone traditionally had to be taken as an injection, which greatly limited its clinical application. In contrast, the new compound can be taken orally. This offers hope for the development of a new field of peptidomimetics for orally-available nonpeptide small molecules. Today, the ever-growing prevalence of major diseases worldwide is driving growth in new drug spending, encouraging the marketing of newly developed and effi cacious

  1. Cost-effectiveness of methadone maintenance treatment for HIV-positive drug users in Vietnam.

    PubMed

    Tran, Bach Xuan; Ohinmaa, Arto; Duong, Anh Thuy; Do, Nhan Thi; Nguyen, Long Thanh; Mills, Steve; Houston, Stan; Jacobs, Philip

    2012-01-01

    Methadone maintenance treatment (MMT) is efficacious in reducing drug use that may improve HIV/AIDS care and treatment outcomes. This study evaluated the incremental cost-effectiveness of MMT for HIV-positive drug users from the perspective of health service providers. A sample of 370 HIV-positive drug users (age: mean ± SD: 29.5 ± 5.9 years; 95.7% male) taking MMT in multi-sites was assessed at baseline, three, six and nine months. Costs of MMT services were analyzed and converted to the year 2009. Quality-adjusted life years (QALYs) were modeled from changes in health-related quality of life of patients using the modified World Health Organization Quality of Life - Brief Version (WHOQOL-BREF). Inverse probability-of-treatment weights, constructed using propensity score of non-responses, were applied to adjust for potential confounding. Over nine months, MMT substantially improved QALYs of HIV/AIDS patients (0.076 QALY [0.066-0.084]). The increments in QALY were large and stabilized in those patients taking antiretroviral treatment and abstinent to drug use. For one QALY gained, the MMT program would cost US$3745.3, approximately 3.2 times Vietnam GDP per capita in 2009. The cost-effectiveness of MMT intervention was robust against HIV advanced status or co-morbidity, e.g., TB treatment, but it might not be cost-effective for those patients who continued to use drug. Findings of this study indicate that providing MMT for HIV-positive drug users is a cost-effective intervention in Vietnam. Integrating MMT to HIV/AIDS care and treatment services would be beneficial in injection-driven HIV epidemics.

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

    PubMed Central

    Macklin, Ruth; Cowan, Ethan

    2013-01-01

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

  3. Eligibility of persons who inject drugs for treatment of hepatitis C virus infection

    PubMed Central

    Arain, Amber; Robaeys, Geert

    2014-01-01

    In this decade, an increase is expected in end-stage liver disease and hepatocellular carcinoma, most commonly caused by hepatitis C virus (HCV) infection. Although people who inject drugs (PWID) are the major source for HCV infection, they were excluded from antiviral treatments until recently. Nowadays there is incontrovertible evidence in favor of treating these patients, and substitution therapy and active substance use are no longer contraindications for antiviral treatment. The viral clearance in PWID after HCV antiviral treatment with interferon or pegylated interferon combined with ribavirin is comparable to the viral clearance in non-substance users. Furthermore, multidisciplinary approaches to delivering treatment to PWID are advised, and their treatment should be considered on an individualized basis. To prevent the spread of HCV in the PWID community, recent active PWID are eligible for treatment in combination with needle exchange programs and substitution therapy. As the rate of HCV reinfection is low after HCV antiviral treatment, there is no need to withhold HCV treatment due to concerns about reinfection alone. Despite the advances in treatment efficacies and data supporting their success, HCV assessment of PWID and initiation of antiviral treatment remains low. However, the proportion of PWID assessed and treated for HCV is increasing, which can be further enhanced by understanding the barriers to and facilitators of HCV care. Removing stigmatization and implementing peer support and group treatment strategies, in conjunction with greater involvement by nurse educators/practitioners, will promote greater treatment seeking and adherence by PWID. Moreover, screening can be facilitated by noninvasive methods for detecting HCV antibodies and assessing liver fibrosis stages. Recently, HCV clearance has become a major endpoint in the war against drugs for the Global Commission on Drug Policy. This review highlights the most recent evidence concerning

  4. Stemming the tide of drug-resistant Neisseria gonorrhoeae: the need for an individualized approach to treatment.

    PubMed

    Buono, Sean A; Watson, Tyler D; Borenstein, Lee A; Klausner, Jeffrey D; Pandori, Mark W; Godwin, Hilary A

    2015-02-01

    Drug-resistant Neisseria gonorrhoeae poses a significant public health challenge. In recent years, gonococci resistant to first- and second-line antibiotics have spread worldwide and new strains have developed that are increasingly resistant to third-generation cephalosporins, which are currently our last line of available treatments. Given the timeline required to develop new drugs or an effective vaccine for N. gonorrhoeae, a top priority is to use the drugs that are available as effectively as possible. Currently, clinical management of gonorrhoea is based upon treatment guidelines informed by international gonococcal antimicrobial susceptibility surveillance programmes. This approach, although currently the most practical, is subject to a number of limitations since surveillance data inherently provide population-level information. As a result, basing treatment guidelines on these data can result in the prescription of more aggressive or broader treatment than is needed by individual patients and hence inadvertently contribute to the development and spread of resistance to important drugs. Clearly, methods are needed that provide patient-specific drug susceptibility information in a time frame that would allow clinicians to prescribe individualized treatment regimens for gonorrhoea. Fortunately, in recent years, there have been a number of advances in the development of rapid methods for characterizing both the genotype and the drug resistance phenotype of N. gonorrhoeae strains. Here, we review these advances and propose additional studies that would help facilitate a transition towards an individualized treatment approach for gonorrhoea.

  5. Illicit Drug Use and Treatment in South Africa

    PubMed Central

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

    2008-01-01

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

  6. Drug rechallenge and treatment beyond progression—implications for drug resistance

    PubMed Central

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

    2015-01-01

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

  7. [Advances in the research of treatment of hydrofluoric acid burn].

    PubMed

    Wang, Xin-gang; Zhang, Yuan-hai; Han, Chun-mao

    2013-08-01

    Hydrofluoric acid (HF) is one of the most common inorganic acids used widely in industrial circle. HF not only causes cutaneous burn, but also induces systemic toxicity by its unique injury mechanism. Accurate and timely diagnosis and treatment are critical after HF burns. To date, the strategies for treating HF burns have been developed, mainly including topical treatments and systematic support. However, there is no standard treatment strategy with wide acceptance in the world. This paper presents a comprehensive overview of the advances in the research of strategies for the treatment of HF burns.

  8. Integrating Multiscale Modeling with Drug Effects for Cancer Treatment

    PubMed Central

    Li, Xiangfang L.; Oduola, Wasiu O.; Qian, Lijun; Dougherty, Edward R.

    2015-01-01

    In this paper, we review multiscale modeling for cancer treatment with the incorporation of drug effects from an applied system’s pharmacology perspective. Both the classical pharmacology and systems biology are inherently quantitative; however, systems biology focuses more on networks and multi factorial controls over biological processes rather than on drugs and targets in isolation, whereas systems pharmacology has a strong focus on studying drugs with regard to the pharmacokinetic (PK) and pharmacodynamic (PD) relations accompanying drug interactions with multiscale physiology as well as the prediction of dosage-exposure responses and economic potentials of drugs. Thus, it requires multiscale methods to address the need for integrating models from the molecular levels to the cellular, tissue, and organism levels. It is a common belief that tumorigenesis and tumor growth can be best understood and tackled by employing and integrating a multifaceted approach that includes in vivo and in vitro experiments, in silico models, multiscale tumor modeling, continuous/discrete modeling, agent-based modeling, and multiscale modeling with PK/PD drug effect inputs. We provide an example application of multiscale modeling employing stochastic hybrid system for a colon cancer cell line HCT-116 with the application of Lapatinib drug. It is observed that the simulation results are similar to those observed from the setup of the wet-lab experiments at the Translational Genomics Research Institute. PMID:26792977

  9. Treatment Approaches for Interoceptive Dysfunctions in Drug Addiction

    PubMed Central

    Paulus, Martin P.; Stewart, Jennifer L.; Haase, Lori

    2013-01-01

    There is emerging evidence that individuals with drug addiction have dysfunctions in brain systems that are important for interoceptive processing, which include, among others, the insular and the anterior cingulate cortices. These individuals may not be expending sufficient neural resources to process perturbations of the interoceptive state but may exert over-activation of these systems when processing drug-related stimuli. As a consequence, insufficient detection and processing of interoceptive state changes may result in inadequate anticipation and preparation to adapt to environmental challenges, e.g., adapt to abstinence in the presence of withdrawal symptoms. Here, we integrate interoceptive dysfunction in drug-addicted individuals, with the neural basis for meditation and exercise to develop a heuristic to target the interoceptive system as potential treatments for drug addiction. First, it is suggested that mindfulness-based approaches can modulate both interoceptive function and insular activation patterns. Second, there is an emerging literature showing that the regulation of physical exercise in the brain involves the insula and anterior cingulate cortex and that intense physical exercise is associated with a insula changes that may provide a window to attenuate the increased interoceptive response to drug-related stimuli. It is concluded that the conceptual framework of interoceptive dysfunctions in drug addiction and the experimental findings in meditation and exercise provide a useful approach to develop new interventions for drug addiction. PMID:24151471

  10. Advances in algal drug research with emphasis on enzyme inhibitors.

    PubMed

    Rengasamy, Kannan R R; Kulkarni, Manoj G; Stirk, Wendy A; Van Staden, Johannes

    2014-12-01

    Enzyme inhibitors are now included in all kinds of drugs essential to treat most of the human diseases including communicable, metabolic, cardiovascular, neurological diseases and cancer. Numerous marine algae have been reported to be a potential source of novel enzyme inhibitors with various pharmaceutical values. Thus, the purpose of this review is to brief the enzyme inhibitors from marine algae of therapeutic potential to treat common diseases. As per our knowledge this is the first review for the potential enzyme inhibitors from marine origin. This review contains 86 algal enzyme inhibitors reported during 1989-2013 and commercial enzyme inhibitors available in the market. Compounds in the review are grouped according to the disease conditions in which they are involved; diabetes, obesity, dementia, inflammation, melanogenesis, AIDS, hypertension and other viral diseases. The structure-activity relationship of most of the compounds are also discussed. In addition, the drug likeness properties of algal inhibitors were evaluated using Lipinski's 'Rule of Five'. PMID:25195189

  11. Drug-Induced Liver Injury during Antidepressant Treatment: Results of AMSP, a Drug Surveillance Program

    PubMed Central

    Friedrich, Michaela-Elena; Akimova, Elena; Huf, Wolfgang; Konstantinidis, Anastasios; Papageorgiou, Konstantinos; Winkler, Dietmar; Toto, Sermin; Greil, Waldemar; Grohmann, Renate; Kasper, Siegfried

    2016-01-01

    Background: Drug-induced liver injury is a common cause of liver damage and the most frequent reason for withdrawal of a drug in the United States. The symptoms of drug-induced liver damage are extremely diverse, with some patients remaining asymptomatic. Methods: This observational study is based on data of Arzneimittelsicherheit in der Psychiatrie, a multicenter drug surveillance program in German-speaking countries (Austria, Germany, and Switzerland) recording severe drug reactions in psychiatric inpatients. Of 184234 psychiatric inpatients treated with antidepressants between 1993 and 2011 in 80 psychiatric hospitals, 149 cases of drug-induced liver injury (0.08%) were reported. Results: The study revealed that incidence rates of drug-induced liver injury were highest during treatment with mianserine (0.36%), agomelatine (0.33%), and clomipramine (0.23%). The lowest probability of drug-induced liver injury occurred during treatment with selective serotonin reuptake inhibitors ([0.03%), especially escitalopram [0.01%], citalopram [0.02%], and fluoxetine [0.02%]). The most common clinical symptoms were nausea, fatigue, loss of appetite, and abdominal pain. In contrast to previous findings, the dosage at the timepoint when DILI occurred was higher in 7 of 9 substances than the median overall dosage. Regarding liver enzymes, duloxetine and clomipramine were associated with increased glutamat-pyruvat-transaminase and glutamat-oxalat-transaminase values, while mirtazapine hardly increased enzyme values. By contrast, duloxetine performed best in terms of gamma-glutamyl-transferase values, and trimipramine, clomipramine, and venlafaxine performed worst. Conclusions: Our findings suggest that selective serotonin reuptake inhibitors are less likely than the other antidepressants, examined in this study, to precipitate drug-induced liver injury, especially in patients with preknown liver dysfunction. PMID:26721950

  12. Recent advances in stealth coating of nanoparticle drug delivery systems

    PubMed Central

    Amoozgar, Zohreh; Yeo, Yoon

    2011-01-01

    Modifying surfaces of nanoparticles (NPs) with polyethylene glycol (PEG), the so called PEGylation, is the most commonly used method for reducing premature clearance of NPs from the circulation. However, several reports point out that PEGylation may negatively influence the performance of NPs as a drug carrier. Alternative surface modification strategies, including substitute polymers, conditional removal of PEG, and biomimetic surface modification, may provide solutions for the limitations of PEG. PMID:22231928

  13. Predicting Drug Court Treatment Completion Using the MMPI-2-RF

    ERIC Educational Resources Information Center

    Mattson, Curtis; Powers, Bradley; Halfaker, Dale; Akeson, Steven; Ben-Porath, Yossef

    2012-01-01

    We examined the ability of the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008) substantive scales to predict Drug Court treatment completion in a sample of individuals identified as being at risk for failure to complete the program. Higher scores on MMPI-2-RF scales Behavior/Externalizing…

  14. Costs of drugs for treatment of rheumatic diseases

    PubMed Central

    Westhovens, Rene; Annemans, Lieven

    2016-01-01

    The cost of drugs is becoming an issue worldwide, in particular for inflammatory rheumatic diseases. In the current review, an overview of the scene is given with a specific emphasis on accessibility for those patients in real need of the available expensive treatments. The authors propose 7 principles for discussion that need to be addressed and are a responsibility for all stakeholders in rheumatology.

  15. New Treatment for Drug-Abusing Women Offenders in Virginia.

    ERIC Educational Resources Information Center

    Clement, Mary

    1997-01-01

    Compares a new approach to treatment using traditional social work. Reports on the therapeutic regimen and Results/Kinesiology (RK), which addresses body-mind control, brain hemispheric integration, energy balancing, and stress elimination. Examination of 40 women addicted to alcohol and/or drugs indicated that RK helped with anxiety,…

  16. Recent advances in combinatorial biosynthesis for drug discovery

    PubMed Central

    Sun, Huihua; Liu, Zihe; Zhao, Huimin; Ang, Ee Lui

    2015-01-01

    Because of extraordinary structural diversity and broad biological activities, natural products have played a significant role in drug discovery. These therapeutically important secondary metabolites are assembled and modified by dedicated biosynthetic pathways in their host living organisms. Traditionally, chemists have attempted to synthesize natural product analogs that are important sources of new drugs. However, the extraordinary structural complexity of natural products sometimes makes it challenging for traditional chemical synthesis, which usually involves multiple steps, harsh conditions, toxic organic solvents, and byproduct wastes. In contrast, combinatorial biosynthesis exploits substrate promiscuity and employs engineered enzymes and pathways to produce novel “unnatural” natural products, substantially expanding the structural diversity of natural products with potential pharmaceutical value. Thus, combinatorial biosynthesis provides an environmentally friendly way to produce natural product analogs. Efficient expression of the combinatorial biosynthetic pathway in genetically tractable heterologous hosts can increase the titer of the compound, eventually resulting in less expensive drugs. In this review, we will discuss three major strategies for combinatorial biosynthesis: 1) precursor-directed biosynthesis; 2) enzyme-level modification, which includes swapping of the entire domains, modules and subunits, site-specific mutagenesis, and directed evolution; 3) pathway-level recombination. Recent examples of combinatorial biosynthesis employing these strategies will also be highlighted in this review. PMID:25709407

  17. Recent advances in combinatorial biosynthesis for drug discovery.

    PubMed

    Sun, Huihua; Liu, Zihe; Zhao, Huimin; Ang, Ee Lui

    2015-01-01

    Because of extraordinary structural diversity and broad biological activities, natural products have played a significant role in drug discovery. These therapeutically important secondary metabolites are assembled and modified by dedicated biosynthetic pathways in their host living organisms. Traditionally, chemists have attempted to synthesize natural product analogs that are important sources of new drugs. However, the extraordinary structural complexity of natural products sometimes makes it challenging for traditional chemical synthesis, which usually involves multiple steps, harsh conditions, toxic organic solvents, and byproduct wastes. In contrast, combinatorial biosynthesis exploits substrate promiscuity and employs engineered enzymes and pathways to produce novel "unnatural" natural products, substantially expanding the structural diversity of natural products with potential pharmaceutical value. Thus, combinatorial biosynthesis provides an environmentally friendly way to produce natural product analogs. Efficient expression of the combinatorial biosynthetic pathway in genetically tractable heterologous hosts can increase the titer of the compound, eventually resulting in less expensive drugs. In this review, we will discuss three major strategies for combinatorial biosynthesis: 1) precursor-directed biosynthesis; 2) enzyme-level modification, which includes swapping of the entire domains, modules and subunits, site-specific mutagenesis, and directed evolution; 3) pathway-level recombination. Recent examples of combinatorial biosynthesis employing these strategies will also be highlighted in this review.

  18. Is immunotherapy an opportunity for effective treatment of drug addiction?

    PubMed

    Zalewska-Kaszubska, Jadwiga

    2015-11-27

    Immunotherapy has a great potential of becoming a new therapeutic strategy in the treatment of addiction to psychoactive drugs. It may be used to treat addiction but also to prevent neurotoxic complications of drug overdose. In preclinical studies two immunological methods have been tested; active immunization, which relies on the administration of vaccines and passive immunization, which relies on the administration of monoclonal antibodies. Until now researchers have succeeded in developing vaccines and/or antibodies against addiction to heroin, cocaine, methamphetamine, nicotine and phencyclidine. Their effectiveness has been confirmed in preclinical studies. At present, clinical studies are being conducted for vaccines against nicotine and cocaine and also anti-methamphetamine monoclonal antibody. These preclinical and clinical studies suggest that immunotherapy may be useful in the treatment of addiction and drug overdose. However, there are a few problems to be solved. One of them is controlling the level of antibodies due to variability between subjects. But even obtaining a suitable antibody titer does not guarantee the effectiveness of the vaccine. Additionally, there is a risk of intentional or unintentional overdose. As vaccines prevent passing of drugs through the blood/brain barrier and thereby prevent their positive reinforcement, some addicted patients may erroneously seek higher doses of psychoactive substances to get "high". Consequently, vaccination should be targeted at persons who have a strong motivation to free themselves from drug dependency. It seems that immunotherapy may be an opportunity for effective treatment of drug addiction if directed to adequate candidates for treatment. For other addicts, immunotherapy may be a very important element supporting psycho- and pharmacotherapy. PMID:26432911

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

    PubMed Central

    Zajdel, Justyna

    2013-01-01

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

  20. Surgical treatment: Myomectomy and hysterectomy; Endoscopy: A major advancement.

    PubMed

    Thubert, Thibault; Foulot, Hervé; Vinchant, Marie; Santulli, Pietro; Marzouk, Paul; Borghese, Bruno; Chapron, Charles

    2016-07-01

    Uterine fibroids affect 25% of women worldwide. Symptomatic women can be treated by either medical or surgical treatment. Development of endoscopic surgery has widely changed the management of myoma. Currently, although laparoscopic or laparoscopic robot-assisted myomectomies or hysterectomies are common, there has been no consensual guideline concerning the surgical techniques, operative route, and usefulness of preoperative treatment. Hysteroscopy management is a major advancement avoiding invasive surgery. This study deals with a literature review concerning surgical management of fibroids. PMID:27400649

  1. Ultrasonic-Activated Micellar Drug Delivery for Cancer Treatment

    PubMed Central

    Husseini, Ghaleb A.; Pitt, William G.

    2008-01-01

    The use of nanoparticles and ultrasound in medicine continues to evolve. Great strides have been made in the areas of producing micelles, nanoemulsions and solid nanoparticles that can be used in drug delivery. An effective nanocarrier allows for the delivery of a high concentration of potent medications to targeted tissue while minimizing the side effect of the agent to the rest of the body. Polymeric micelles have been shown to encapsulate therapeutic agents and maintain their structural integrity at lower concentrations. Ultrasound is currently being used in drug delivery as well as diagnostics, and has many advantages that elevate its importance in drug delivery. The technique is non-invasive, thus no surgery is needed; the ultrasonic waves can be easily controlled by advanced electronic technology so that they can be focused on the desired target volume. Additionally, the physics of ultrasound are widely used and well understood; thus ultrasonic application can be tailored towards a particular drug delivery system. In this article, we review the recent progress made in research that utilizes both polymeric micelles and ultrasonic power in drug delivery. PMID:18506804

  2. Recent Advances in the Treatment of Isosexual Precocious Puberty

    PubMed Central

    Leung, Alexander K.C.; McArthur, Robert G.

    1991-01-01

    In isosexual precocious puberty, the changes that characterize puberty occur in roughly the same order, but at a much earlier age. The causes and clinical features of isosexual precocity and their evaluation and treatment are discussed in this article, the purpose of which is to provide a general review of the disorder, taking into account recent advances in its management. PMID:20469522

  3. Advanced oxidation processes with coke plant wastewater treatment.

    PubMed

    Krzywicka, A; Kwarciak-Kozłowska, A

    2014-01-01

    The aim of this study was to determine the most efficient method of coke wastewater treatment. This research examined two processes - advanced oxidation with Fenton and photo-Fenton reaction. It was observed that the use of ultraviolet radiation with Fenton process had a better result in removal of impurities.

  4. Advanced Waste Treatment. A Field Study Training Program.

    ERIC Educational Resources Information Center

    California State Univ., Sacramento. Dept. of Civil Engineering.

    This operations manual represents a continuation of operator training manuals developed for the United States Environmental Protection Agency (USEPA) in response to the technological advancements of wastewater treatment and the changing needs of the operations profession. It is intended to be used as a home-study course manual (using the concepts…

  5. Advances in developing alternative treatments for postharvest pest control

    Technology Transfer Automated Retrieval System (TEKTRAN)

    USDA-ARS made two significant advances in the last 10 years in the development of alternative treatments for postharvest pest control: oxygenated phosphine fumigation and nitric oxide fumigation. Oxygenated phosphine is phosphine fumigation in an oxygen enriched atmosphere. It is significantly more...

  6. Predictors of drug treatment completion among parole violators.

    PubMed

    Zanis, David A; Coviello, Donna M; Lloyd, Jacqueline J; Nazar, Barry L

    2009-06-01

    This study examined the predictors of treatment completion among 380 state parole violators consecutively admitted to a comprehensive 12-month drug treatment program in lieu of reincarceration. Offenders were placed on intensive parole supervision throughout the 12-month treatment protocol and received three months of residential substance abuse treatment followed by nine months of outpatient counseling. Overall 123 (32.4%) of the offenders completed the 12-month treatment protocol. The primary reason for noncompletion was a positive drug screen. Bivariate analyses were performed to determine independent predictors of program completion. Four variables (age, past 30-day heroin use, total months incarcerated, and significant problems with mother) from the baseline Addiction Severity Index were found to be correlated with treatment completion (p <.10). These factors and other demographics (race, marital status, education) and variables found predictive of program completion in previous studies were entered into a multiple logistic regression model. Overall the final model found that only two factors--older age (p < .03) and no heroin use in the past 30 days (p < .02) significantly predicted treatment completion. These findings suggest that among parolees with moderate to extensive criminal justice histories younger individuals and those with recent heroin use respond less favorably to comprehensive substance abuse treatment services and intensive parole supervision.

  7. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy.

    PubMed

    Pérez-Herrero, Edgar; Fernández-Medarde, Alberto

    2015-06-01

    Cancer is the second worldwide cause of death, exceeded only by cardiovascular diseases. It is characterized by uncontrolled cell proliferation and an absence of cell death that, except for hematological cancers, generates an abnormal cell mass or tumor. This primary tumor grows thanks to new vascularization and, in time, acquires metastatic potential and spreads to other body sites, which causes metastasis and finally death. Cancer is caused by damage or mutations in the genetic material of the cells due to environmental or inherited factors. While surgery and radiotherapy are the primary treatment used for local and non-metastatic cancers, anti-cancer drugs (chemotherapy, hormone and biological therapies) are the choice currently used in metastatic cancers. Chemotherapy is based on the inhibition of the division of rapidly growing cells, which is a characteristic of the cancerous cells, but unfortunately, it also affects normal cells with fast proliferation rates, such as the hair follicles, bone marrow and gastrointestinal tract cells, generating the characteristic side effects of chemotherapy. The indiscriminate destruction of normal cells, the toxicity of conventional chemotherapeutic drugs, as well as the development of multidrug resistance, support the need to find new effective targeted treatments based on the changes in the molecular biology of the tumor cells. These novel targeted therapies, of increasing interest as evidenced by FDA-approved targeted cancer drugs in recent years, block biologic transduction pathways and/or specific cancer proteins to induce the death of cancer cells by means of apoptosis and stimulation of the immune system, or specifically deliver chemotherapeutic agents to cancer cells, minimizing the undesirable side effects. Although targeted therapies can be achieved directly by altering specific cell signaling by means of monoclonal antibodies or small molecules inhibitors, this review focuses on indirect targeted approaches that

  8. Advances in Treatment Integrity Research: Multidisciplinary Perspectives on the Conceptualization, Measurement, and Enhancement of Treatment Integrity

    ERIC Educational Resources Information Center

    Schulte, Ann C.; Easton, Julia E.; Parker, Justin

    2009-01-01

    Documenting treatment integrity is an important issue in research and practice in any discipline concerned with prevention and intervention. However, consensus concerning the dimensions of treatment integrity and how they should be measured has yet to emerge. Advances from three areas in which significant treatment integrity work has taken…

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

    ERIC Educational Resources Information Center

    Beschner, George M., Ed.; And Others

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

  10. Current therapeutic strategies of anti-HER2 treatment in advanced breast cancer patients

    PubMed Central

    Nowara, Elżbieta

    2016-01-01

    The HER2/neu (ERBB2) oncogene is amplified and/or overexpressed in approximately 20% of breast cancers, and is a strong prognostic factor for relapse and poor overall survival, particularly in node-positive patients. It is also an important predictor for response to trastuzumab, which has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. Treatment with the anti-HER2 humanized monoclonal antibody – trastuzumab significantly improves progression-free and overall survival among patients with HER2-positive breast cancer. However, in most patients with HER2-positive metastatic breast cancer, the disease progresses occurred, what cause the need for new targeted therapies for advanced disease. In clinical trials, there are tested new drugs to improve the results of treatment for this group of patients. This paper presents new drugs introduced into clinical practice for treatment of advanced breast cancer, whose molecular target are receptors of the HER2 family. In addition, new therapeutic strategies and drugs that are currently in clinical researches are discussed. PMID:27095932

  11. Variation in drug injection frequency among out-of-treatment drug users in a national sample.

    PubMed

    Singer, M; Himmelgreen, D; Dushay, R; Weeks, M R

    1998-05-01

    This article analyzes data on drug injection frequency in a sample of more than 13,000 out-of-treatment drug injectors interviewed across 21 U.S. cities and Puerto Rico through the National Institute on Drug Abuse (NIDA) Cooperative Agreement for AIDS Community-Based Outreach/Intervention Research Program. The goals of the article are to present findings on injection frequency and to predict variation in terms of a set of variables suggested by previous research, including location, ethnicity, gender, age, educational attainment, years since first use of alcohol and marijuana, income, living arrangement, homelessness, drugs injected, and duration of injection across drugs. Three models were tested. Significant intersite differences were identified in injection frequency, although most of the other predictor variables we tested accounted for little of the variance. Ethnicity and drugs injected, however, were found to be significant. Taken together, location, ethnicity, and type of drug injected provide a configuration that differentiated and (for the variables available for the analysis) best predicted injection frequency. The public health implications of these findings are presented.

  12. Delamanid expanded access novel treatment of drug resistant tuberculosis

    PubMed Central

    Rustomjee, Roxana; Zumla, Alimuddin

    2015-01-01

    Tuberculosis (TB) remains a global emergency and is one of the most common infectious disease causes of death in developing countries. Current treatment regimens for multi-drug resistant TB are associated with low treatment success rates, are toxic, and require long duration of treatment. The need for shorter and more effective treatment regimens is urgent. Delamanid (Deltyba, or formerly known as OPC-67683) is a new dihydro-imidazooxazole anti-TB drug active against resistant forms of pulmonary TB. Delamanid kills Mycobacterium tuberculosis by inhibiting the synthesis of mycolic acids required for cell wall synthesis. Whilst delamanid has been included in the WHO Model List of Essential Medicine by the World Health Organization Expert Committee on Selection and Use of Essential Medicines and in international guidance for the treatment of multi-drug resistant TB since April 2014, its access in countries with the greatest need, has proven challenging. This review provides an update on currently available clinical safety and efficacy data on delamanid and offers a discussion on research priorities and recommendations for expedited, expanded access. PMID:26604805

  13. Cardiovascular impact of drugs used in the treatment of diabetes

    PubMed Central

    Ding, Hong

    2014-01-01

    The International Diabetes Federation predicts that by 2035 10% of the population of the world will have been diagnosed with diabetes, raising serious concerns over the resulting elevated morbidity and mortality as well as the impact on health care budgets. It is also well recognized that cardiovascular disease is the primary cause of the high morbidity and mortality associated with diabetes, raising the concern that appropriate drug therapy should not only correct metabolic dysfunction, but also protect the cardiovascular system from the effects of, in particular, the epigenetic changes that result from hyperglycaemia. A number of new classes of drugs for the treatment of diabetes have been introduced in the past decade, providing the opportunity to optimize treatment; however, comparative information of the cardiovascular benefits, or risks, of the newer drugs versus older therapies such as metformin is variable. This review, in addition to summarizing the cellular basis for the therapeutic action of these drugs, addresses the evidence for their cardiovascular benefits and risks. A particular focus is provided on metformin as it is the first choice drug for most patients with type 2 diabetes. PMID:25364492

  14. Cardiovascular impact of drugs used in the treatment of diabetes.

    PubMed

    Triggle, Chris R; Ding, Hong

    2014-11-01

    The International Diabetes Federation predicts that by 2035 10% of the population of the world will have been diagnosed with diabetes, raising serious concerns over the resulting elevated morbidity and mortality as well as the impact on health care budgets. It is also well recognized that cardiovascular disease is the primary cause of the high morbidity and mortality associated with diabetes, raising the concern that appropriate drug therapy should not only correct metabolic dysfunction, but also protect the cardiovascular system from the effects of, in particular, the epigenetic changes that result from hyperglycaemia. A number of new classes of drugs for the treatment of diabetes have been introduced in the past decade, providing the opportunity to optimize treatment; however, comparative information of the cardiovascular benefits, or risks, of the newer drugs versus older therapies such as metformin is variable. This review, in addition to summarizing the cellular basis for the therapeutic action of these drugs, addresses the evidence for their cardiovascular benefits and risks. A particular focus is provided on metformin as it is the first choice drug for most patients with type 2 diabetes. PMID:25364492

  15. Drug treatment refusal and length of hospitalization of insanity acquittees.

    PubMed

    Williams, M H; Bloom, J D; Faulkner, L R; Rogers, J L; Godard, S L

    1988-01-01

    Thirty-three insanity acquittees who had refused drug treatment were matched to a sample of nonrefusing hospitalized insanity acquittees in an attempt to measure the effect of treatment refusal on length of hospital stay. No measurable effects on the length of hospitalization were found. However, upon comparing the amount of time under court jurisdiction spent in the hospital and on conditional release in the community, it becomes evident that refusers spent significantly greater proportions of time hospitalized than the average hospitalized insanity acquittee, who had less hospitalization and spent more time on conditional release. These differences do not seem to be related to the issue of treatment refusal.

  16. Safety of drugs used in the treatment of osteoporosis.

    PubMed

    McGreevy, Cora; Williams, David

    2011-08-01

    A number of drug classes are licensed for the treatment of osteoporosis including bisphosphonates, recombinant human parathyroid hormone (PTH), strontium, hormone replacement therapy (HRT), selective oestrogen receptor modulators (SERMS) and denosumab. This review discusses the safety of osteoporosis treatments and their efficacies. Recent concerns about the safety of calcium and high-dose vitamin D are discussed. Bisphosphonates have substantial postmarketing experience and a clearer picture of safety issues is emerging. Along with the well recognized effects on the gastrointestinal tract and kidney function, recently described adverse effects such as osteonecrosis of the jaw, oesophageal cancer, atrial fibrillation, subtrochanteric femur fractures and ocular complications of bisphosphonate therapy are discussed. Therapy with PTH is limited to two years' duration because of the development of osteogenic sarcomas in animal studies, which appeared related to dose, duration and timing of therapy. Strontium should be used with caution in patients with renal impairment and its use has been associated with venous thromboembolism. The role of HRT and SERMs in the treatment of postmenopausal osteoporosis is restricted as a result of an increased risk of stroke, venous thromboembolism and breast cancer. Postmarketing experience with denusomab is limited but a number of potential safety concerns including osteonecrosis of the jaw are emerging. All of these drugs have been proven to reduce fractures. The decision to use a drug to reduce fracture risk should be based on risk-benefit analysis of the drug and its suitability for individual patients. PMID:25083210

  17. Psychobiology and the treatment of drug dependence: the biobehavioral interface.

    PubMed

    Meyer, R E

    1986-01-01

    In the past 15 years there has been an explosion of data on the multivariate nature of drug dependence. The complex relationship between addictive disorders and psychopathology has been better clarified. Certain Axis I and II diagnoses in DSM-III appear to occur more commonly in alcohol- and drug-dependent patients than in the general population, suggesting that they may serve as risk factors for the development of addictive disorders. Psychopathological symptoms also result during periods of chronic intoxication and may persist as secondary psychiatric disorders even in the absence of continued substance use. Behavioral research in human and animal models has begun to yield insights into the nature of dependence disorders and the importance of brain mechanisms of reinforcement to the addiction process. Inevitably, neural scientists are beginning to delineate the commonalities and differences in drug reinforcement across drug class. The research has begun to suggest pharmacological approaches to the treatment of drug dependence and withdrawal. This paper provides an overview of research on the psychobiology of drug dependence with implications for the clinician.

  18. Treatment programs in the National Drug Abuse Treatment Clinical Trials Network.

    PubMed

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

    2008-01-01

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

  19. Treatment Programs in the National Drug Abuse Treatment Clinical Trials Network

    PubMed Central

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

    2008-01-01

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

  20. Agonist treatment in opioid use: advances and controversy.

    PubMed

    Viswanath, Biju; Chand, Prabhat; Benegal, Vivek; Murthy, Pratima

    2012-06-01

    Opioid dependence is a chronic relapsing condition which requires comprehensive care; pharmacological agents form the mainstay of its long term treatment. The two most popular approaches are the harm reduction method using agonists and the complete abstinence method using antagonists. Currently, particularly from the harm minimization perspective and the low feasibility of an abstinence based approach, there is an increasing trend toward agonist treatment. The use of buprenorphine has gained popularity in view of its safety profile and the availability of the buprenorphine-naloxone combination has made it popular as a take-home treatment. This review outlines the pharmacological advances and controversies in this area. PMID:22813654

  1. Critical evaluation of ramucirumab in the treatment of advanced gastric and gastroesophageal cancers.

    PubMed

    ElHalawani, Hesham; Abdel-Rahman, Omar

    2015-01-01

    Gastric (GC) and gastroesophageal junction (GEJ) cancers are two global health problems with a relatively high mortality, particularly in the advanced stage. Inhibition of angiogenesis is now contemplated as a classic treatment preference for myriad tumor types encompassing renal cell carcinoma, non-small cell lung cancer, colorectal cancer, glioblastoma, and ovarian cancer, among others. Bevacizumab and ramucirumab have been widely investigated in GC and GEJ cancer, with some controversy about their therapeutic role. Ramucirumab is a monoclonal antibody for vascular endothelial growth factor receptor-2, with demonstrated activity both as a monotherapy and as a part of combination strategy in the management of advanced GC/GEJ cancer. In this review article, we present a critical evaluation of the preclinical and clinical data underlying the use of this drug in this indication. Moreover, we provide a spotlight on the future perspectives in systemic therapy for advanced GC/GEJ cancer.

  2. Critical evaluation of ramucirumab in the treatment of advanced gastric and gastroesophageal cancers

    PubMed Central

    ElHalawani, Hesham; Abdel-Rahman, Omar

    2015-01-01

    Gastric (GC) and gastroesophageal junction (GEJ) cancers are two global health problems with a relatively high mortality, particularly in the advanced stage. Inhibition of angiogenesis is now contemplated as a classic treatment preference for myriad tumor types encompassing renal cell carcinoma, non-small cell lung cancer, colorectal cancer, glioblastoma, and ovarian cancer, among others. Bevacizumab and ramucirumab have been widely investigated in GC and GEJ cancer, with some controversy about their therapeutic role. Ramucirumab is a monoclonal antibody for vascular endothelial growth factor receptor-2, with demonstrated activity both as a monotherapy and as a part of combination strategy in the management of advanced GC/GEJ cancer. In this review article, we present a critical evaluation of the preclinical and clinical data underlying the use of this drug in this indication. Moreover, we provide a spotlight on the future perspectives in systemic therapy for advanced GC/GEJ cancer. PMID:26251608

  3. [New drugs in the treatment of multiple myeloma].

    PubMed

    Oriol, Albert; Motlló, Cristina

    2014-09-15

    Progress in the treatment of multiple myeloma in the last decade has been able to delay, but ultimately not to prevent, the development of resistances and most patients still die of the disease or its related complications. New drugs have been developed including new alkylating agents, proteasome inhibitors and immunomodulators but also monoclonal antibodies and drugs with new mechanisms of action. Hopefully, this new generation of targeted agents will improve the results of the initial therapy, avoid relapses and development of resistances and provide better and less toxic options for the relapsed and refractory patient. PMID:24342015

  4. [New drugs for the treatment of human parasitic protozoa].

    PubMed

    Dupouy-Camet, J

    2004-06-01

    Whereas parasitic diseases are always a heavy burden for humanity, few are the new antiparasitic molecules marketed during the last 25 years. Thus on the 1393 new molecules marketed between 1975 and 1999, only 7 have antiprotozoan properties. This talk will detail the progress made in the treatment of the intestinal protozoa, malaria, visceral leishmaniasis and toxoplasmosis, problems with which are especially confronted the European parasitologists. The treatment of Giardia and intestinal amoebas is based on 5-nitro-imidazoles derivatives. Single-dose treatments can be used with tinidazole or secnidazole. Resistance to these compounds of Giardia were described and in these cases, treatment by quinacrine or nitazoxanide are possible alternatives. Nitazoxanide is marketed in the United States and in Australia. It seems to be a well tolerated antiparasitic agent with a broad spectrum because it is active on a lot of intestinal protozoa and helminths. It acts on the same metabolic way as the 5-nitro-imidazoles (inhibition of the ferredoxine reductase) but without synthesis of free radicals and DNA deterioration of the target cell. It is thus neither teratogenic nor mutagenic. Artemisinin derivatives allowed considerable progress in the treatment of malaria. They have short half-lifes, allowing a fast parasitic clearance and these derivatives do no provoke resistance. They are first line drugs for the treatment of malaria in areas of drug resistance. The arthemeter-lumefantrine association (Riamet, Coartem) ensures a rapid disappearance of the circulating parasites and is well tolerated. Atovaquone-proguanil (Malarone) is usable in the treatment of acute malaria but also in disease prevention with the advantage of continuing drug intake for only 7 days after having left the infected area. The treatment of leishmaniasis is always delicate and is characterized by the worrying development of antimony resistances, probably related in the European zones to the treatment of

  5. Advances in the treatment of inherited coagulation disorders.

    PubMed

    Escobar, M A

    2013-09-01

    Inherited coagulation disorders constitute a broad spectrum of coagulation factor deficiencies that include X-linked factor (F)VIII or FIX deficiency that causes haemophilia, and autosomal recessive disorders producing heterogeneous deficiencies in fibrinogen (FI), prothrombin (FII), FV, FVII, FX, FXI, FXIII and combined FV+FVIII. Significant advances in treatments for patients with congenital haemophilia A (FVIII deficiency) and B (FIX deficiency) over the last two decades have resulted from improvements in the production, availability and patient access to factor replacement products. Translation of advances in biotechnology, namely recombinant protein technology, targeted protein modifications to improve function and potentially reduce immunogenicity, and advanced formulations to optimize bioavailability and sustain activity offer promisingly new treatments for haemophilia as well as recessively inherited bleeding disorders in patients who otherwise have few therapeutic options. Though a theoretical risk remains for blood-borne viral infections with pooled plasma-derived products, this concern has diminished with breakthroughs in purification and viral inactivation methods. Development of inhibitory antibodies is still the most daunting problem for patients with inherited bleeding disorders, complicating treatment approaches to control and prevent bleeding, and posing risks for allergic and anaphylactic reactions in susceptible patients. The objectives of this review are to (i) highlight emerging advances in hemostatic therapies that are bioengineered to improve pharmacokinetic properties and bioavailability, sustain functional activity, and possibly eliminate immunogenicity of recombinant factor proteins; and (ii) present an overview of key clinical trials of novel factor products currently in the development pipeline.

  6. Reassessing the Role of Intra-Arterial Drug Delivery for Glioblastoma Multiforme Treatment

    PubMed Central

    Ellis, Jason A.; Banu, Matei; Hossain, Shaolie S.; Singh-Moon, Rajinder; Lavine, Sean D.; Bruce, Jeffrey N.; Joshi, Shailendra

    2015-01-01

    Effective treatment for glioblastoma (GBM) will likely require targeted delivery of several specific pharmacological agents simultaneously. Intra-arterial (IA) delivery is one technique for targeting the tumor site with multiple agents. Although IA chemotherapy for glioblastoma (GBM) has been attempted since the 1950s, the predicted benefits remain unproven in clinical practice. This review focuses on innovative approaches to IA drug delivery in treating GBM. Guided by novel in vitro and in vivo optical measurements, newer pharmacokinetic models promise to better define the complex relationship between background cerebral blood flow and drug injection parameters. Advanced optical technologies and tracers, unique nanoparticles designs, new cellular targets, and rational drug formulations are continuously modifying the therapeutic landscape for GBM. Personalized treatment approaches are emerging; however, such tailored approaches will largely depend on effective drug delivery techniques and on the ability to simultaneously deliver multidrug regimens. These new paradigms for tumor-selective drug delivery herald dramatic improvements in the effectiveness of IA chemotherapy for GBM. Therefore, within this context of so-called “precision medicine,” the role of IA delivery for GBM is thoroughly reassessed. PMID:26819758

  7. Basics and recent advances in peptide and protein drug delivery

    PubMed Central

    Bruno, Benjamin J; Miller, Geoffrey D; Lim, Carol S

    2014-01-01

    While the peptide and protein therapeutic market has developed significantly in the past decades, delivery has limited their use. Although oral delivery is preferred, most are currently delivered intravenously or subcutaneously due to degradation and limited absorption in the gastrointestinal tract. Therefore, absorption enhancers, enzyme inhibitors, carrier systems and stability enhancers are being studied to facilitate oral peptide delivery. Additionally, transdermal peptide delivery avoids the issues of the gastrointestinal tract, but also faces absorption limitations. Due to proteases, opsonization and agglutination, free peptides are not systemically stable without modifications. This review discusses oral and transdermal peptide drug delivery, focusing on barriers and solutions to absorption and stability issues. Methods to increase systemic stability and site-specific delivery are also discussed. PMID:24228993

  8. Romidepsin: a new drug for the treatment of cutaneous T-cell lymphoma.

    PubMed

    Frye, Robin; Myers, Mary; Axelrod, Karen C; Ness, Elizabeth A; Piekarz, Richard L; Bates, Susan E; Booher, Susan

    2012-04-01

    Patients with cutaneous T-cell lymphoma (CTCL) have a rare, disfiguring, and life-threatening subtype of non-Hodgkin lymphoma primarily localized to the skin. Their immune systems are altered and their skin is compromised. In addition, they are highly prone to infections-the most common cause of death in patients with this disease. Patients presenting with early-stage disease involvement typically are treated with topical therapies; patients with advanced-stage and recurrent disease require systemic treatment. Specialized knowledge is required by oncology healthcare providers to manage the wide array of symptoms experienced by these patients as a part of the natural course of this disease. A new drug, romidepsin, approved by the U.S. Food and Drug Administration, is indicated in the treatment of relapsed CTCL. The authors discuss use of romidepsin in the context of CTCL and the information needed to safely administer romidepsin and manage its side effects.

  9. Adolescent drug misuse treatment and use of medical care services.

    PubMed

    Freeborn, D K; Polen, M R; Mullooly, J P

    1995-05-01

    Research on adults has documented that use of medical services decreases after initiation of treatment for alcohol problems, but little is known about this relationship among adolescents. We studied utilization and costs of care following participation in the Adolescent Chemical Health Program (ACHP) of Kaiser Permanente, Northwest Region, in 1986-88. Three groups of adolescents (and their parents) were identified: adolescents who were assessed and initiated treatment in ACHP (n = 561), adolescents who were assessed and recommended for treatment but did not return for treatment (n = 278), and adolescents with no known substance use problems (n = 381). Medical records were reviewed for 1 year pre- and 1.5 years postassessment. After adjusting for preassessment medical visits, severity of alcohol and drug use, gender, and age, analyses suggested that substance user treatment was not associated with reduced use of medical services or costs by either adolescents or parents. PMID:7558471

  10. Oral health behavior of drug addicts in withdrawal treatment

    PubMed Central

    2013-01-01

    Background Oral health behavior (OHB), one major factor contributing to proper oral health status, has been addressed insufficiently in addiction literature. The aim of our study was to investigate OHB and its determinants among drug addicts in withdrawal treatment. Methods Through a stratified cluster sampling method, we collected the data from 685 patients in withdrawal treatment in Tehran using self-administered questionnaires on OHB components and conducting interviews about patients’ characteristics and addiction history. The T-test, ANOVA, and a linear regression model served for statistical analysis. Results Of the patients, 48% reported brushing their teeth less than once a day, more than 90% used fluoride toothpaste almost or always, and 81% flossed their teeth rarely or never. Eating sugary products twice a day or more was reported by 57% of the patients and 85% of them were current smokers. Poor OHB was associated with male gender, lower education, being addicted mainly to crystalline heroin, starting drug abuse at a younger age, and having a longer history of addiction (p < .05). Conclusion Poor OHB was found among the participants in drug withdrawal treatment. Preventive strategies on oral health should be planned and be integrated into other health promotion programs for addicts along with their withdrawal treatment taking into account special groups at higher risk. PMID:23368406

  11. Advances in device and formulation technologies for pulmonary drug delivery.

    PubMed

    Chan, John Gar Yan; Wong, Jennifer; Zhou, Qi Tony; Leung, Sharon Shui Yee; Chan, Hak-Kim

    2014-08-01

    Inhaled pharmaceuticals are formulated and delivered differently according to the therapeutic indication. However, specific device-formulation coupling is often fickle, and new medications or indications also demand new strategies. The discontinuation of chlorofluorocarbon propellants has seen replacement of older metered dose inhalers with dry powder inhaler formulations. High-dose dry powder inhalers are increasingly seen as an alternative dosage form for nebulised medications. In other cases, new medications have completely bypassed conventional inhalers and been formulated for use with unique inhalers such as the Staccato® device. Among these different devices, integration of software and electronic assistance has become a shared trend. This review covers recent device and formulation advances that are forming the current landscape of inhaled therapeutics. PMID:24728868

  12. The XIIth International Symposium on Recent Advances in Drug Delivery Systems.

    PubMed

    Vivès, Eric

    2005-05-01

    The XIIth International Symposium on Recent Advances in Drug Delivery Systems was held from 21-24 February 2005 in Salt Lake City, UT, USA. Approximately 250 people attended this symposium dedicated to a broad variety of topics, ranging from recent advances in drug delivery systems to biomaterials and novel concepts in macromolecular therapeutics. A total of 33 people, all recognised specialists in the aforementioned fields, presented 30-min up-to-date reviews of these topics, as well as discussing recent results. In addition, the symposium included a poster session with approximately 100 displays highlighting various interesting data. PMID:16296778

  13. Liposome-based drug delivery in breast cancer treatment

    PubMed Central

    Park, John W

    2002-01-01

    Drug delivery systems can in principle provide enhanced efficacy and/or reduced toxicity for anticancer agents. Long circulating macromolecular carriers such as liposomes can exploit the 'enhanced permeability and retention' effect for preferential extravasation from tumor vessels. Liposomal anthracyclines have achieved highly efficient drug encapsulation, resulting in significant anticancer activity with reduced cardiotoxicity, and include versions with greatly prolonged circulation such as liposomal daunorubicin and pegylated liposomal doxorubicin. Pegylated liposomal doxorubucin has shown substantial efficacy in breast cancer treatment both as monotherapy and in combination with other chemotherapeutics. Additional liposome constructs are being developed for the delivery of other drugs. The next generation of delivery systems will include true molecular targeting; immunoliposomes and other ligand-directed constructs represent an integration of biological components capable of tumor recognition with delivery technologies. PMID:12052251

  14. Modeling mass drug treatment and resistant filaria disease transmission

    NASA Astrophysics Data System (ADS)

    Fuady, A. M.; Nuraini, N.; Soewono, E.; Tasman, H.; Supriatna, A. K.

    2014-03-01

    It has been indicated that a long term application of combined mass drug treatment may contribute to the development of drug resistance in lymphatic filariasis. This phenomenon is not well understood due to the complexity of filaria life cycle. In this paper we formulate a mathematical model for the spread of mass drug resistant in a filaria endemic region. The model is represented in a 13-dimensional Host-Vector system. The basic reproductive ratio of the system which is obtained from the next generation matrix, and analysis of stability of both the disease free equilibrium and the coexistence equilibria are shown. Numerical simulation for long term dynamics for possible field conditions is also shown.

  15. MRI-detectable polymeric micelles incorporating platinum anticancer drugs enhance survival in an advanced hepatocellular carcinoma model

    PubMed Central

    Vinh, Nguyen Quoc; Naka, Shigeyuki; Cabral, Horacio; Murayama, Hiroyuki; Kaida, Sachiko; Kataoka, Kazunori; Morikawa, Shigehiro; Tani, Tohru

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most intractable and lethal cancers; most cases are diagnosed at advanced stages with underlying liver dysfunction and are frequently resistant to conventional chemotherapy and radiotherapy. The development of tumor-targeting systems may improve treatment outcomes. Nanomedicine platforms are of particular interest for enhancing chemotherapeutic efficiency, and they include polymeric micelles, which enable targeting of multiple drugs to solid tumors, including imaging and therapeutic agents. This allows concurrent diagnosis, targeting strategy validation, and efficacy assessment. We used polymeric micelles containing the T1-weighted magnetic resonance imaging contrast agent gadolinium-diethylenetriaminpentaacetic acid (Gd-DTPA) and the parent complex of the anticancer drug oxaliplatin [(1,2-diaminocyclohexane)platinum(II) (DACHPt)] for simultaneous imaging and therapy in an orthotopic rat model of HCC. The Gd-DTPA/DACHPt-loaded micelles were injected into the hepatic artery, and magnetic resonance imaging performance and antitumor activity against HCC, as well as adverse drug reactions were assessed. After a single administration, the micelles achieved strong and specific tumor contrast enhancement, induced high levels of tumor apoptosis, and significantly suppressed tumor size and growth. Moreover, the micelles did not induce severe adverse reactions and significantly improved survival outcomes in comparison to oxaliplatin or saline controls. Our results suggest that Gd-DTPA/DACHPt-loaded micelles are a promising approach for effective diagnosis and treatment of advanced HCC. PMID:26203241

  16. [Recent advances in medical and surgical treatment of ulcerative colitis].

    PubMed

    Sugita, Akira; Koganei, Kazutaka; Tatsumi, Kenji; Futatsuki, Ryo; Kuroki, Hirosuke; Yamada, Kyoko; Arai, Katsuhiko; Fukushima, Tsuneo

    2015-03-01

    Recent advances in both medical and surgical treatment of ulcerative colitis have been remarkable. Changes in medical treatment are mainly good results of therapy with the anti-TNF-α antibody, tacrolimus, and those in surgical treatment are an expansion of the surgical indications to include patients with intractable disease, such as treatment refractoriness and chronic corticosteroid dependence, by a better postoperative clinical course after pouch surgery, improred selection of surgical procedures and the timing of surgery in elderly patients. To offer the optimal treatment for patients with ulcerative colitis, new medical therapies should be analyzed from the standpoint of the efficacy and limitations of effect. Long postoperative clinical course of surgical patients including colitic cancer, prevention of postoperative complications should be also analyzed.

  17. Sequence of treatment in locally advanced and metastatic renal cell carcinoma

    PubMed Central

    Fischer, Stefanie; Gillessen, Silke

    2015-01-01

    The spectrum of drugs that have shown activity in advanced or metastatic renal cell carcinoma (RCC) has led to a debate on the optimal sequence of treatments. There is agreement on recommending targeted agents as the standard of care in this disease. Uncertainty, however, remains on the best first-line drug choice. Physicians and patients may select sunitinib, bevacizumab in combination with interferon-alpha (IFN-α), pazopanib, or—in poor risk patients—temsirolimus. There are also a variety of therapies with proven efficacy on hand in the second-line setting: sorafenib, pazopanib, axitinib, and everolimus. While most randomized RCC trials assessed progression free survival (PFS) as primary endpoint, some agents were shown to improve median overall survival (OS), and given in sequence they have extended the life expectancy of RCC patients from 13 months in the cytokine era to over 30 months. Despite the progress made, there are sobering aspects to the oncologic success story in RCC, as the new treatments do not obtain an objective response or disease stabilization (SD) in all patients. There are also as yet no predictors to select patients who might benefit and those who are primary resistant to specific drugs, and ultimately almost all patients will experience disease progression. Bearing inevitable treatment failure in mind, availability of further drugs and switching therapy while the patient is in a condition to continue pharmacotherapy is essential. Of note, depending on the setting, only 33-59% of patients receive second-line treatment. In this review we present data on first-, second-, and third-line treatment in RCC, and discuss the difficulties in their interpretation in the context of treatment sequence. We summarize biological aspects and discuss mechanisms of resistance to anti-angiogenic therapy and their implications for treatment selection. PMID:26816832

  18. Treatment for hepatitis B in patients with drug resistance

    PubMed Central

    Kroy, Daniela C.

    2016-01-01

    Persistent hepatitis B virus (HBV) infections affect about 240 million patients worldwide that are at risk of developing liver cirrhosis or hepatocellular carcinoma. HBV is a small, partially double stranded DNA virus with four overlapping genes and a unique life cycle, which involves the generation of an RNA template for replication via reverse transcription. Mutations occur frequently during chronic infection, and particular selection pressures select distinct mutants. Nucleoside and nucleotide analogues like lamivudine (LMV), entecavir (ETV), telbivudine (LdT), adefovir dipivoxil (ADV) and tenofovir (TDF) are used to achieve long-term suppression of viral replication. Importantly, these drugs have different barriers to resistance, explaining the higher incidence of treatment failure in the past due to drug resistant viral strains for the older compounds LMV, LdT and ADV. On a molecular level, drug resistant mutations usually affect the reverse transcriptase domain of the HBV polymerase protein. Secondary compensatory mutations restore the replication fitness of the mutant virus. From a clinical point of view, patients undergoing antiviral therapy require regular testing for HBV DNA (every 3–6 months). In case of insufficient viral suppression or viral breakthrough (>1 log increase in HBV DNA above nadir), strict adherence to therapy needs to be ensured. If drug resistance is suspected or even molecularly confirmed, rescue therapy strategies exist, usually switching to a noncross-resistant antiviral drug. LMV, LdT and ETV resistant HBV can be treated with TDF monotherapy, ADV resistance with ETV or TDF, and insufficient responses to TDF may require ETV either as mono- or combination therapy. Complex treatment histories with many antivirals may sometimes necessitate the combination of highly effective antivirals like ETV and TDF. Novel treatment targets such as core (capsid) inhibitors, siRNA targeting protein translation, entry inhibitors or immune modulators

  19. Advances in the treatment of varicella-zoster virus infections.

    PubMed

    Andrei, G; Snoeck, R

    2013-01-01

    Varicella-zoster virus (VZV) causes two distinct diseases, varicella (chickenpox) and shingles (herpes zoster). Chickenpox occurs subsequent to primary infection, while herpes zoster (usually associated with aging and immunosuppression) appears as a consequence of reactivation of latent virus. The major complication of shingles is postherpetic neuralgia. Vaccination strategies to prevent varicella or shingles and the current status of antivirals against VZV will be discussed in this chapter. Varivax®, a live-attenuated vaccine, is available for pediatric varicella. Zostavax® is used to boost VZV-specific cell-mediated immunity in adults older than 50 years, which results in a decrease in the burden of herpes zoster and pain related to postherpetic neuralgia. Regardless of the availability of a vaccine, new antiviral agents are necessary for treatment of VZV infections. Current drugs approved for therapy of VZV infections include nucleoside analogues that target the viral DNA polymerase and depend on the viral thymidine kinase for their activation. Novel anti-VZV drugs have recently been evaluated in clinical trials, including the bicyclic nucleoside analogue FV-100, the helicase-primase inhibitor ASP2151, and valomaciclovir (prodrug of the acyclic guanosine derivative H2G). Different candidate VZV drugs have been described in recent years. New anti-VZV drugs should be as safe as and more effective than current gold standards for the treatment of VZV, that is, acyclovir and its prodrug valacyclovir.

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

    PubMed Central

    Fecher, Leslie A; Sharfman, William H

    2015-01-01

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

  1. Virus Reduction during Advanced Bardenpho and Conventional Wastewater Treatment Processes.

    PubMed

    Schmitz, Bradley W; Kitajima, Masaaki; Campillo, Maria E; Gerba, Charles P; Pepper, Ian L

    2016-09-01

    The present study investigated wastewater treatment for the removal of 11 different virus types (pepper mild mottle virus; Aichi virus; genogroup I, II, and IV noroviruses; enterovirus; sapovirus; group-A rotavirus; adenovirus; and JC and BK polyomaviruses) by two wastewater treatment facilities utilizing advanced Bardenpho technology and compared the results with conventional treatment processes. To our knowledge, this is the first study comparing full-scale treatment processes that all received sewage influent from the same region. The incidence of viruses in wastewater was assessed with respect to absolute abundance, occurrence, and reduction in monthly samples collected throughout a 12 month period in southern Arizona. Samples were concentrated via an electronegative filter method and quantified using TaqMan-based quantitative polymerase chain reaction (qPCR). Results suggest that Plant D, utilizing an advanced Bardenpho process as secondary treatment, effectively reduced pathogenic viruses better than facilities using conventional processes. However, the absence of cell-culture assays did not allow an accurate assessment of infective viruses. On the basis of these data, the Aichi virus is suggested as a conservative viral marker for adequate wastewater treatment, as it most often showed the best correlation coefficients to viral pathogens, was always detected at higher concentrations, and may overestimate the potential virus risk. PMID:27447291

  2. Advanced drug delivery systems of curcumin for cancer chemoprevention.

    PubMed

    Bansal, Shyam S; Goel, Mehak; Aqil, Farrukh; Vadhanam, Manicka V; Gupta, Ramesh C

    2011-08-01

    Since ancient times, chemopreventive agents have been used to treat/prevent several diseases including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, antioxidant, antiproliferative, anticarcinogenic, and antiangiogenic activity in various cell cultures and some animal studies. Research over the past 4 decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been shown to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician's armamentarium. PMID:21546540

  3. Advanced Drug-Delivery Systems of Curcumin for Cancer Chemoprevention

    PubMed Central

    Bansal, Shyam S.; Goel, Mehak; Aqil, Farrukh; Vadhanam, Manicka V.; Gupta, Ramesh C.

    2011-01-01

    From ancient times, chemopreventive agents have been used to treat/prevent several diseases, including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, anti-oxidant, anti-proliferative, anti-carcinogenic, and anti-angiogenic activity in various cell culture and some animal studies. Research over the past four decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell-culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been demonstrated to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician’s armamentarium. PMID:21546540

  4. Emerging drugs for the treatment of chronic obstructive pulmonary disease.

    PubMed

    Malhotra, Samir; Man, S F Paul; Sin, Don D

    2006-05-01

    By 2020 chronic obstructive pulmonary disease (COPD) will be the third leading cause of mortality and fifth leading cause of morbidity. Research over the past two decades has shed important insights on the pathobiology of COPD, leading to the development of novel drugs. In the past, symptomatic treatment with bronchodilators was the predominant focus of COPD management. With increased awareness of the importance of airway inflammation in COPD progression, there has been a shift in emphasis to drugs that attack various targets in the inflammatory cascade. These drugs include phosphodiesterase 4 inhibitors, leukotriene modifiers and TNF antagonists, which are poised to enter the COPD market in the very near future. Tyrosine kinase antagonists, inhibitors of NF-kappaB, neutrophil elastase inhibitors, chemokine antagonists, mucolytics and novel antibiotics are being evaluated for possible effectiveness in COPD. Many of these drugs may enter the COPD market within the next decade. This paper reviews the molecular rationale for these emerging drugs and their potential efficacy in COPD.

  5. Costs of drugs for treatment of rheumatic diseases.

    PubMed

    Westhovens, Rene; Annemans, Lieven

    2016-01-01

    The cost of drugs is becoming an issue worldwide, in particular for inflammatory rheumatic diseases. In the current review, an overview of the scene is given with a specific emphasis on accessibility for those patients in real need of the available expensive treatments. The authors propose 7 principles for discussion that need to be addressed and are a responsibility for all stakeholders in rheumatology. PMID:27651923

  6. Costs of drugs for treatment of rheumatic diseases

    PubMed Central

    Westhovens, Rene; Annemans, Lieven

    2016-01-01

    The cost of drugs is becoming an issue worldwide, in particular for inflammatory rheumatic diseases. In the current review, an overview of the scene is given with a specific emphasis on accessibility for those patients in real need of the available expensive treatments. The authors propose 7 principles for discussion that need to be addressed and are a responsibility for all stakeholders in rheumatology. PMID:27651923

  7. Clinical use of cabozantinib in the treatment of advanced kidney cancer: efficacy, safety, and patient selection

    PubMed Central

    Yu, Steven S; Quinn, David I; Dorff, Tanya B

    2016-01-01

    Clear cell (cc) renal cell carcinoma (RCC) is the most common type of cancer found in the kidney accounting for ~90% of all kidney cancers. In 2012, there were ~337,000 new cases of RCC diagnosed worldwide with an estimated 143,000 deaths, with the highest incidence and mortality in Western countries. Despite improvements in cancer control achieved with VEGF- and mTOR-targeted therapy for RCC, progression remains virtually universal and additional therapies are needed. The pivotal results of the METEOR trial led to cabozantinib’s designation as a breakthrough drug by the US Food and Drug Administration and its approval for treatment of advanced RCC in 2016. Subsequent data from the CABOSUN trial, where caboxantinib is compared with sunitinib, will provide information on the relative activity of cabozantinib as first-line therapy for ccRCC. We review the development of cabozantinib in advanced RCC and its role in the treatment landscape for advanced RCC. PMID:27713636

  8. Drug Treatment within the U.S. Federal Prison System: Are Treatment Needs Being Met?

    ERIC Educational Resources Information Center

    van Wormer, Katherine; Persson, Lance Edwards

    2010-01-01

    A large percentage of inmates in the U.S. federal prison system have serious drug problems and are in need of treatment before they return to society. Accordingly, the Federal Bureau of Prisons has revamped substance abuse programming consistent with the latest research and expanded treatment services throughout its institutions. This article…

  9. Spotlight on pembrolizumab in the treatment of advanced melanoma.

    PubMed

    Rajakulendran, Thanashan; Adam, David N

    2015-01-01

    Metastatic melanoma is an aggressive cancer with a poor prognosis. Many approved therapies often do not achieve durable responses in patients. This underscores the need for novel therapeutic strategies. Recruiting a robust immune response is an important antineoplastic treatment strategy. Immune checkpoints offer a molecular target for modulating the immune response and a promising therapeutic target in metastatic melanoma. Here we discuss the recent approval of pembrolizumab by the US Food and Drug Administration for the treatment of metastatic melanoma and its impact on future management of the disease.

  10. Warm autoimmune hemolytic anemia: advances in pathophysiology and treatment.

    PubMed

    Michel, M

    2014-04-01

    Autoimmune hemolytic anemia due to warm antibodies (wAIHA) accounts for approximately 70% to 80% of all AIHAs in adults. The pathogenesis of wAIHA is a complex multistep process, the last step of which being the abnormal production of auto-antibodies directed towards red blood cells' membrane antigens. The recent advances in the understanding of the underlying mechanisms leading to the breakdown of self-tolerance in wAIHA, mainly thanks to the study of animal models are discussed in this review. Treatment of wAIHA has long been empirical and mainly based on corticosteroids. In the last decade however, the efficacy of rituximab as second-line treatment has been demonstrated first in retrospective and more recently throughout prospective studies. Based on these advances, an algorithm for the management of primary adult's wAIHA is proposed in this review.

  11. Locally Advanced Gastroesophageal Junction Tumor: A Treatment Dilemma

    PubMed Central

    Ashraf, Noman; Hoffe, Sarah

    2015-01-01

    Over the last several decades, the incidence of adenocarcinoma of the gastroesophageal junction (GEJ) has been increasing in developed countries. Although complete surgical resection remains the cornerstone of treatment for resectable disease, long-term outcomes are poor and recurrence rates are high with surgery alone in patients presenting with locally advanced disease. Multimodal therapy has been shown to improve survival; however, the optimal therapeutic approach remains controversial, and practices vary across the world. Preoperative chemoradiotherapy is generally used in the U.S., whereas perioperative chemotherapy without radiation is favored in most European countries. In this review, we discuss why the treatment of locally advanced GEJ tumors remains controversial, examine the evidence for various multimodal approaches, discuss their respective pros and cons, evaluate the role of radiation therapy, highlight some ongoing and planned clinical trials, and suggest areas that need further research. PMID:25561508

  12. Advancing drug discovery for neuropsychiatric disorders using patient-specific stem cell models.

    PubMed

    Haggarty, Stephen J; Silva, M Catarina; Cross, Alan; Brandon, Nicholas J; Perlis, Roy H

    2016-06-01

    Compelling clinical, social, and economic reasons exist to innovate in the process of drug discovery for neuropsychiatric disorders. The use of patient-specific, induced pluripotent stem cells (iPSCs) now affords the ability to generate neuronal cell-based models that recapitulate key aspects of human disease. In the context of neuropsychiatric disorders, where access to physiologically active and relevant cell types of the central nervous system for research is extremely limiting, iPSC-derived in vitro culture of human neurons and glial cells is transformative. Potential applications relevant to early stage drug discovery, include support of quantitative biochemistry, functional genomics, proteomics, and perhaps most notably, high-throughput and high-content chemical screening. While many phenotypes in human iPSC-derived culture systems may prove adaptable to screening formats, addressing the question of which in vitro phenotypes are ultimately relevant to disease pathophysiology and therefore more likely to yield effective pharmacological agents that are disease-modifying treatments requires careful consideration. Here, we review recent examples of studies of neuropsychiatric disorders using human stem cell models where cellular phenotypes linked to disease and functional assays have been reported. We also highlight technical advances using genome-editing technologies in iPSCs to support drug discovery efforts, including the interpretation of the functional significance of rare genetic variants of unknown significance and for the purpose of creating cell type- and pathway-selective functional reporter assays. Additionally, we evaluate the potential of in vitro stem cell models to investigate early events of disease pathogenesis, in an effort to understand the underlying molecular mechanism, including the basis of selective cell-type vulnerability, and the potential to create new cell-based diagnostics to aid in the classification of patients and subsequent

  13. Advancing drug discovery for neuropsychiatric disorders using patient-specific stem cell models.

    PubMed

    Haggarty, Stephen J; Silva, M Catarina; Cross, Alan; Brandon, Nicholas J; Perlis, Roy H

    2016-06-01

    Compelling clinical, social, and economic reasons exist to innovate in the process of drug discovery for neuropsychiatric disorders. The use of patient-specific, induced pluripotent stem cells (iPSCs) now affords the ability to generate neuronal cell-based models that recapitulate key aspects of human disease. In the context of neuropsychiatric disorders, where access to physiologically active and relevant cell types of the central nervous system for research is extremely limiting, iPSC-derived in vitro culture of human neurons and glial cells is transformative. Potential applications relevant to early stage drug discovery, include support of quantitative biochemistry, functional genomics, proteomics, and perhaps most notably, high-throughput and high-content chemical screening. While many phenotypes in human iPSC-derived culture systems may prove adaptable to screening formats, addressing the question of which in vitro phenotypes are ultimately relevant to disease pathophysiology and therefore more likely to yield effective pharmacological agents that are disease-modifying treatments requires careful consideration. Here, we review recent examples of studies of neuropsychiatric disorders using human stem cell models where cellular phenotypes linked to disease and functional assays have been reported. We also highlight technical advances using genome-editing technologies in iPSCs to support drug discovery efforts, including the interpretation of the functional significance of rare genetic variants of unknown significance and for the purpose of creating cell type- and pathway-selective functional reporter assays. Additionally, we evaluate the potential of in vitro stem cell models to investigate early events of disease pathogenesis, in an effort to understand the underlying molecular mechanism, including the basis of selective cell-type vulnerability, and the potential to create new cell-based diagnostics to aid in the classification of patients and subsequent

  14. Surgical adjuvant treatment of locally advanced breast cancer.

    PubMed Central

    Townsend, C M; Abston, S; Fish, J C

    1985-01-01

    The reported incidence of local recurrence after mastectomy for locally advanced breast cancer (TNM Stage III and IV) is between 30% and 50%. The purpose of this study was to evaluate the effect of radiation therapy (XRT) followed by total mastectomy on the incidence of local recurrence in patients with locally advanced breast cancer. Fifty-three patients who presented with locally advanced breast cancer, without distant metastases, were treated with XRT (4500-5000 R) to the breast, chest wall, and regional lymph nodes. Five weeks after completion of XRT, total mastectomy was performed. There were no operative deaths. The complications that occurred in 22 patients after surgery were flap necrosis, wound infection, and seroma. Patients have been followed from 3 to 134 months. Twenty-five patients are alive (3-134 months), 12 free of disease; 28 patients have died with distant metastases (6-67 months). Isolated local recurrence occurred in only two patients. Four patients had local and distant recurrence (total local recurrence is 6/53). The remaining patients all developed distant metastases. We have devised a treatment strategy which significantly decreases the incidence of local recurrence in patients with locally advanced breast cancer. However, the rapid appearance of distant metastases emphasizes the need for systemically active therapy in patients with locally advanced breast cancer. PMID:3994434

  15. Advancement in treatment and diagnosis of pancreatic cancer with radiopharmaceuticals

    PubMed Central

    Xu, Yu-Ping; Yang, Min

    2016-01-01

    Pancreatic cancer (PC) is a major health problem. Conventional imaging modalities show limited accuracy for reliable assessment of the tumor. Recent researches suggest that molecular imaging techniques with tracers provide more biologically relevant information and are benefit for the diagnosis of the cancer. In addition, radiopharmaceuticals also play more important roles in treatment of the disease. This review summaries the advancement of the radiolabeled compounds in the theranostics of PC. PMID:26909131

  16. Evaluation of advanced oxidation process for the treatment of groundwater

    SciTech Connect

    Garland, S.B. II ); Peyton, G.R. ); Rice, L.E. . Kansas City Div.)

    1990-01-01

    An advanced oxidation process utilizing ozone, ultraviolet radiation, and hydrogen peroxide was selected for the removal of chlorinated hydrocarbons, particularly trichlorethene and 1,2-dichlorethene, from groundwater underlying the US Department of Energy Kansas City Plant. Since the performance of this process for the removal of organics from groundwater is not well-documented, an evaluation was initiated to determine the performance of the treatment plant, document the operation and maintenance costs experience, and evaluate contaminant removal mechanisms. 11 refs., 3 figs.

  17. Early Gastric Cancer: Current Advances of Endoscopic Diagnosis and Treatment.

    PubMed

    Zhu, Linlin; Qin, Jinyu; Wang, Jin; Guo, Tianjiao; Wang, Zijing; Yang, Jinlin

    2016-01-01

    Endoscopy is a major method for early gastric cancer screening because of its high detection rate, but its diagnostic accuracy depends heavily on the availability of endoscopic instruments. Many novel endoscopic techniques have been shown to increase the diagnostic yield of early gastric cancer. With the improved detection rate of EGC, the endoscopic treatment has become widespread due to advances in the instruments available and endoscopist's experience. The aim of this review is to summarize frequently-used endoscopic diagnosis and treatment in early gastric cancer (EGC). PMID:26884753

  18. Drug insight: Recent advances in male hormonal contraception.

    PubMed

    Amory, John K; Page, Stephanie T; Bremner, William J

    2006-01-01

    As there are limitations to current methods of male contraception, research has been undertaken to develop hormonal contraceptives for men, analogous to the methods for women based on estrogen and progestogens. When testosterone is administered to a man, it functions as a contraceptive by suppressing the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland. Since these hormones are the main stimulatory signals for spermatogenesis, low levels of LH and FSH markedly impair sperm production. After 3-4 months of testosterone treatment, 60-70% of men no longer have sperm in their ejaculate, and most other men exhibit markedly diminished sperm counts. Male hormonal contraception is well tolerated, free of serious adverse side effects, and 95% effective in the prevention of pregnancy. Importantly, male hormonal contraception is reversible, with sperm counts usually recovering within 4 months of the discontinuation of hormone treatment. Because exogenous testosterone administration alone does not completely suppress sperm production in all men, researchers have combined testosterone with second agents, such as progestogens or gonadotropin-releasing-hormone antagonists, to further suppress secretion of LH and FSH and improve suppression of spermatogenesis. Recent trials have used combinations of long-acting injectable or implantable forms of testosterone with progestogens, which can be administered orally, by injection or by a long-acting implant. Such combinations suppress spermatogenesis to zero without severe side effects in 80-90% of men, with near-complete suppression in the remainder of individuals. One of these testosterone and progestogen combination regimens might soon bring the promise of male hormonal contraception to fruition. PMID:16932251

  19. Drug treatments for schizophrenia: pragmatism in trial design shows lack of progress in drug design.

    PubMed

    Cheng, F; Jones, P B

    2013-09-01

    Aims. The introduction of second generation antipsychotic (SGA) medication over a decade ago led to changes in prescribing practices; these drugs have eclipsed their predecessors as treatments for schizophrenia. However, the metabolic side effects of these newer antipsychotics have been marked and there are increasing concerns as to whether these novel drugs really are superior to their predecessors in terms of the balance between risks and benefits. In this article, we review the literature regarding comparisons between first generation antipsychotic (FGA) and SGA in terms of clinical effectiveness. Methods. Large (n > 150) randomized-controlled trials (RCTs) comparing the effectiveness (efficacy and side effects) of FGA and SGA medications other than clozapine were reviewed, as were meta-analyses that included smaller studies. Results. The superiority in efficacy and reduced extrapyramidal side effects (EPSE) of SGAs is modest, especially when compared with low-dose FGAs. However, the high risk of weight gain and other metabolic disturbances associated with certain SGAs such as olanzapine is markedly higher than the risk with FGAs at the doses used in the trials. Conclusions. The efficacy profiles of various FGAs and SGAs are relatively similar, but their side effects vary between and within classes. Overall, large pragmatic trials of clinical effectiveness indicate that the care used in prescribing and managing drug treatments to ensure tolerability may be more important than the class of drug used.

  20. [Prevention and treatment of hepatitis C in illicit drug users].

    PubMed

    Sakoman, Slavko

    2009-12-01

    Drug use is a complex behavior with multidimensional determinants, including social, psychological, cultural, economic, and biological factors. Blood borne viral infections including hepatitis C virus are transmitted when an uninfected intravenous drug user (IVDU) uses injection equipment, especially syringes, that have previously been used by an infected person. The transmission can also result from sharing other injection equipment such as 'cookers' and 'cottons'. Recent studies have shown that the prevalence and incidence of drug abuse have declined substantially since the introduction of needle exchange. Infection with hepatitis C may spontaneously resolve during the acute stage and never progress to chronic infection, or the infection may become chronic without medical complications, or the infection may become chronic with progressive medical complications. Regular testing for infection is an important strategy for secondary prevention of chronic hepatitis C infection. Care for hepatitis C is a vital component of a comprehensive health program for persons using illicit drugs. Such care includes screening for transmission risk behavior, prevention counseling and education, testing for HCV antibody and RNA. IDUs found to have chronic HCV infection should be assessed for the presence and degree of liver disease and evaluated for treatment for HCV Hepatitis C care also requires providing access to treatment for substance use and abuse. Therapy with opioid agonists, including methadone maintenance treatment, has been shown to diminish and often eliminate opioid use and reduce transmission of infection. Approval of buprenorphine makes office-based pharmacotherapy for opioid addiction possible. When considering treatment for hepatitis C, particular attention must be paid to mental health conditions. As a group, IDUs exhibit higher rates of comorbid psychiatric disorders than the general population. IFN-based regimens for hepatitis C are often complicated by

  1. Targeted treatment of advanced and metastaticbreast cancer with lapatinib

    PubMed Central

    Corkery, Brendan; O’Donovan, Norma; Crown, John

    2008-01-01

    Improved molecular understanding of breast cancer in recent years has led to the discovery of important drug targets such as HER-2 and EGFR. Lapatinib is a potent dual inhibitor of HER-2 and EGFR. Preclinical and phase I studies have shown activity with lapatinib in a number of cancers, including breast cancer, and the drug is well tolerated. The main known drug interactions are with paclitaxel and irinotecan. The most significant side-effects of lapatinib are diarrhea and adverse skin events. Rates of cardiotoxicity compare favorably with trastuzumab, a monoclonal antibody against HER-2. This paper focuses on lapatinib in advanced and metastatic breast cancer, which remains an important therapeutic challenge. Phase II and III studies show activity as monotherapy, and in combination with chemotherapy or hormonal agents. Results from these studies suggest that the main benefit from lapatinib is in the HER-2 positive breast cancer population. Combinations of lapatinib and trastuzumab are also being studied and show encouraging results, particularly in trastuzumab-refractory metastatic breast cancer. Lapatinib may have a specific role in treating HER-2 positive CNS metastases. The role of lapatinib as neoadjuvant therapy and in early breast cancer is also being evaluated. PMID:21127749

  2. ADVANCED TOOLS FOR ASSESSING SELECTED PRESCRIPTION AND ILLICIT DRUGS IN TREATED SEWAGE EFFLUENTS AND SOURCE WATERS

    EPA Science Inventory

    The purpose of this poster is to present the application and assessment of advanced state-of-the-art technologies in a real-world environment - wastewater effluent and source waters - for detecting six drugs [azithromycin, fluoxetine, omeprazole, levothyroxine, methamphetamine, m...

  3. Advancing Alzheimer's disease diagnosis, treatment, and care: recommendations from the Ware Invitational Summit.

    PubMed

    Naylor, Mary D; Karlawish, Jason H; Arnold, Steven E; Khachaturian, Ara S; Khachaturian, Zaven S; Lee, Virginia M-Y; Baumgart, Matthew; Banerjee, Sube; Beck, Cornelia; Blennow, Kaj; Brookmeyer, Ron; Brunden, Kurt R; Buckwalter, Kathleen C; Comer, Meryl; Covinsky, Kenneth; Feinberg, Lynn Friss; Frisoni, Giovanni; Green, Colin; Guimaraes, Renato Maia; Gwyther, Lisa P; Hefti, Franz F; Hutton, Michael; Kawas, Claudia; Kent, David M; Kuller, Lewis; Langa, Kenneth M; Mahley, Robert W; Maslow, Katie; Masters, Colin L; Meier, Diane E; Neumann, Peter J; Paul, Steven M; Petersen, Ronald C; Sager, Mark A; Sano, Mary; Schenk, Dale; Soares, Holly; Sperling, Reisa A; Stahl, Sidney M; van Deerlin, Vivianna; Stern, Yaakov; Weir, David; Wolk, David A; Trojanowski, John Q

    2012-09-01

    To address the pending public health crisis due to Alzheimer's disease (AD) and related neurodegenerative disorders, the Marian S. Ware Alzheimer Program at the University of Pennsylvania held a meeting entitled "State of the Science Conference on the Advancement of Alzheimer's Diagnosis, Treatment and Care," on June 21-22, 2012. The meeting comprised four workgroups focusing on Biomarkers; Clinical Care and Health Services Research; Drug Development; and Health Economics, Policy, and Ethics. The workgroups shared, discussed, and compiled an integrated set of priorities, recommendations, and action plans, which are presented in this article. PMID:22959699

  4. Prosthodontic treatment for a patient with advanced hydantoin-associated gingival hyperplasia: a case report.

    PubMed

    Hayakawa, I; Osada, E; Morisawa, M; Nakagawa, Y; Watanabe, I

    1996-04-01

    A patient in whom gingival hyperplasia was caused by prolonged use of an anticonvulsant drug (hydantoin) is described. Advanced gingival hyperplasia and significant displacement of the remaining teeth caused severe damage, especially to the patient's appearance. It was not possible to cure the problems completely with routine periodontal treatment. It was decided to extract all the remaining teeth and restore function and esthetics early with complete dentures. Cephalometric analysis was used to determine the degree to which the teeth had drifted. During fabrication of the dentures, the analysis was very useful in deciding the position of the anterior teeth and checking the vertical dimension of occlusion.

  5. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2008.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2009-02-01

    This review highlights some of the research advances in anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects and in allergic skin disease that were reported in the Journal in 2008. Key epidemiologic observations include a rise in anaphylaxis in a population-based study and lower rates of peanut allergy in Israel, where infants consume peanut early compared with the United Kingdom, where dietary introduction is generally delayed. Advances in food allergy diagnosis include IgE epitope mapping that discloses the likelihood and severity of allergy; studies correlating likelihood of clinical reactivity on the basis of food-specific IgE to sesame, peanut, milk, and tree nuts; and an observation that a low baseline angiotensin-converting enzyme level may be associated with having pharyngeal edema during a reaction. Molecular, immunologic, and genetic studies are discerning pathways that are key in development of food allergy, identifying new modalities to interrupt mast cell degranulation, and elucidating risks associated with penicillin allergy. Regarding treatment, clinical studies show a majority of children with milk and egg allergy tolerate these proteins in modest amounts when they are extensively heated in baked goods, and studies show promise for oral immunotherapy to treat milk allergy and sublingual immunotherapy for honey bee venom hypersensitivity. The importance of skin barrier dysfunction has continued to be highlighted in the pathophysiology of atopic dermatitis (AD). Research has also continued to identify immunologic defects that contribute to the propensity of patients with AD to develop viral and bacterial infection. New therapeutic approaches to AD, urticaria, and angioedema have been reported including use of probiotics, biologics, vitamin D, and skin barrier creams.

  6. New drugs for the treatment of experimental alcoholism.

    PubMed

    Myers, R D

    1994-01-01

    This article presents a current overview of the efforts to suppress pharmacologically the craving, dependence, or other factors associated with the self-selection of alcohol in an experimental animal. The contemporary status of the pharmacotherapy of experimental alcoholism similarly is described for different animal models of alcohol drinking. An evaluation is presented of several classes of drug for their efficacy in ameliorating the volitional ingestion of alcohol in the presence of an alternative fluid. Currently, two main experimental animal models of alcoholism are being used in this endeavor: (a) genetic lines or substrains of high alcohol preferring or high drinking rats; and (b) strains of nondrinking or low alcohol preferring rats which are induced chemically to prefer alcohol. Because of technical, methodological, and other issues surrounding the procedures used to assess the efficacy of a drug in reducing alcohol intake, several of the newer findings remain controversial. For example, serious side effects on the intake of food, caloric regulation, motor activity, or other functions would preclude the clinical utility of the drug. However, several drugs which affect monoaminergic neurons as well as opioid systems in the brain now seem to offer promise as agents which do possess clinical benefits. Two of these drugs, FG5606 (amperozide) and FG 5893 are essentially "antialcoholic" or anticraving and are without any significant side effects on cerebral mechanisms responsible for hunger, caloric intake, motor activity, or other physiological process. Amperozide, a 5-HT2 receptor antagonist with dopamine releasing properties, is particularly notable because of its irreversible nature in attenuating alcohol preference for months after its administration. It is concluded that future pharmacological research on presently available and newly developed compounds will provide exciting opportunities to the clinician who can utilize a particular drug as an adjunctive

  7. In-silico simulations of advanced drug delivery systems: what will the future offer?

    PubMed

    Siepmann, Juergen

    2013-09-15

    This commentary enlarges on some of the topics addressed in the Position Paper "Towards more effective advanced drug delivery systems" by Crommelin and Florence (2013). Inter alia, the role of mathematical modeling and computer-assisted device design is briefly addressed in the Position Paper. This emerging and particularly promising field is considered in more depth in this commentary. In fact, in-silico simulations have become of fundamental importance in numerous scientific and related domains, allowing for a better understanding of various phenomena and for facilitated device design. The development of novel prototypes of space shuttles, nuclear power plants and automobiles are just a few examples. In-silico simulations are nowadays also well established in the field of pharmacokinetics/pharmacodynamics (PK/PD) and have become an integral part of the discovery and development process of novel drug products. Since Takeru Higuchi published his seminal equation in 1961 the use of mathematical models for the analysis and optimization of drug delivery systems in vitro has also become more and more popular. However, applying in-silico simulations for facilitated optimization of advanced drug delivery systems is not yet common practice. One of the reasons is the gap between in vitro and in vivo (PK/PD) simulations. In the future it can be expected that this gap will be closed and that computer assisted device design will play a central role in the research on, and development of advanced drug delivery systems.

  8. Drug treatment for obesity in the post-sibutramine era.

    PubMed

    Cheung, Bernard M Y

    2011-08-01

    Obesity is a major health problem worldwide. It is associated with cardiovascular diseases, diabetes mellitus and decreased longevity. In managing obesity, diet and exercise are essential; pharmacological therapy may be added for obese patients or overweight patients with cardiovascular risk factors. Sibutramine is a serotonergic and adrenergic drug that reduces food intake and increases thermogenesis. It reduces bodyweight by about 4.2 kg after 12 months, and improves blood glucose and lipids; however, it can increase heart rate and blood pressure. In the SCOUT (Sibutramine Cardiovascular OUTcomes) study, sibutramine increased serious cardiovascular events, such as stroke or myocardial infarction, compared with placebo, and was consequently withdrawn from the market. The lesson learnt from this is the importance of patient selection, limiting the duration of treatment and stopping treatment in non-responders. Currently, phentermine and amfepramone (diethylpropion) are approved for short-term treatment of obesity (up to 3 months) and orlistat is approved for longer-term treatment; however, the gastrointestinal adverse effects of orlistat may be intolerable for some patients. There is now a clear need to find anti-obesity drugs that are effective and safe in the long term.

  9. Clinical management of advanced gastric cancer: The role of new molecular drugs

    PubMed Central

    De Vita, Ferdinando; Di Martino, Natale; Fabozzi, Alessio; Laterza, Maria Maddalena; Ventriglia, Jole; Savastano, Beatrice; Petrillo, Angelica; Gambardella, Valentina; Sforza, Vincenzo; Marano, Luigi; Auricchio, Annamaria; Galizia, Gennaro; Ciardiello, Fortunato; Orditura, Michele

    2014-01-01

    Gastric cancer is the fourth most common malignant neoplasm and the second leading cause of death for cancer in Western countries with more than 20000 new cases yearly diagnosed in the United States. Surgery represents the main approach for this disease but, notwithstanding the advances in surgical techniques, we observed a minimal improvement in terms of overall survival with a significant increasing of relapsing disease rates. Despite the development of new drugs has significantly improved the effectiveness of chemotherapy, the prognosis of patients with unresectable or metastatic gastric adenocarcinoma remains poor. Recently, several molecular target agents have been investigated; in particular, trastuzumab represents the first target molecule showing improvements in overall survival in human epithelial growth factor 2-positive gastric cancer patients. New molecules targeting vascular epithelial growth factor, mammalian target of rapamycin, and anti hepatocyte growth factor-c-Met pathway are also under investigation, with interesting results. Anyway, it seems necessary to select more accurately the population to treat with new agents by the identification of new biomarkers in order to optimize the results. In this paper we review the actual “scenario” of targeted treatments, also focusing on the new agents in development for gastric cancer and gastro-esophageal carcinoma, discussing their efficacy and potential applications in clinical practice. PMID:25356019

  10. New applications of old metal-binding drugs in the treatment of human cancer

    PubMed Central

    Schmitt, Sara M.; Frezza, Michael; Dou, Qing Ping

    2013-01-01

    Significant advances in the use of metal complexes, precipitated by platinum, have fostered a renewed interest in harnessing their rich potential in the treatment of cancer. In addition to platinum-based complexes, the anticancer properties of other metals such as ruthenium have been realized, and ruthenium-based compounds are currently being investigated in clinical trials. Since the process of drug development can be expensive and cumbersome, finding new applications of existing drugs may provide effective means to expedite the regulatory process in bringing new drugs to the clinical setting. Encouraging findings from laboratory studies reveal significant anticancer activity from different classes of metal-chelating compounds, such as disulfiram, clioquinol, and dithiocarbamate derivatives that are currently approved for the treatment of various pathological disorders. Their use as coordination complexes with metals such as copper, zinc, and gold that target the ubiquitin-proteasome pathway have shown significant promise as potential anticancer agents. This review discusses the unique role of several selected metals in relation to their anti-cancer properties as well as the new therapeutic potential of several previously approved metal-chelating drugs. In vitro and in vivo experimental evidence along with mechanisms of action (e.g., via targeting the tumor proteasome) will also be discussed with anticipation of strengthening this exciting new concept. PMID:22202066

  11. 28 CFR 550.56 - Community Transitional Drug Abuse Treatment Program (TDAT).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  12. 28 CFR 550.56 - Community Transitional Drug Abuse Treatment Program (TDAT).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  13. 28 CFR 550.56 - Community Transitional Drug Abuse Treatment Program (TDAT).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  14. Investigational new drugs for the treatment of resistant pneumococcal infections.

    PubMed

    Hoffman-Roberts, Holly L; C Babcock, Emily; Mitropoulos, Isaac F

    2005-08-01

    Antibiotic resistance in Streptococcus pneumoniae is not only increasing with penicillin but also with other antimicrobial classes including the macrolides, tetracyclines and sulfonamides. This trend with antibiotic resistance has highlighted the need for the further development of new anti-infectives for the treatment of pneumococcal infections, particularly against multi-drug resistant pneumococci. Several new drugs with anti-pneumococcal activity are at various stages of development and will be discussed in this review. Two new cephalosporins with activity against S. pneumoniae include ceftobiprole and RWJ-54428. Faropenem is in a new class of beta-lactam antibiotics called the penems. Structurally, the penems are a hybrid between the penicillins and cephalosporins. Sitafloxacin and garenoxacin are two new quinolones that are likely to have a role in treating pneumococcal infections. Oritavancin and dalbavancin are glycopeptides with activity against methicillin-resistant S. aureus and vancomycin-resistant Enterococcus spp. as well as multi-drug resistant pneumococci. Tigecycline is the first drug in a new class of anti-infectives called the glycycyclines that has activity against penicillin-resistant pneumococci. PMID:16050791

  15. Technological advances in the surgical treatment of movement disorders.

    PubMed

    Gross, Robert E; McDougal, Margaret E

    2013-08-01

    Technological innovations have driven the advancement of the surgical treatment of movement disorders, from the invention of the stereotactic frame to the adaptation of deep brain stimulation (DBS). Along these lines, this review will describe recent advances in inserting neuromodulation modalities, including DBS, to the target, and in the delivery of therapy at the target. Recent radiological advances are altering the way that DBS leads are targeted and inserted, by refining the ability to visualize the subcortical targets using high-field strength magnetic resonance imaging and other innovations, such as diffusion tensor imaging, and the development of novel targeting devices enabling purely anatomical implantations without the need for neurophysiological monitoring. New portable computed tomography scanners also are facilitating lead implantation without monitoring, as well as improving radiological verification of DBS lead location. Advances in neurophysiological mapping include efforts to develop automatic target verification algorithms, and probabilistic maps to guide target selection. The delivery of therapy at the target is being improved by the development of the next generation of internal pulse generators (IPGs). These include constant current devices that mitigate the variability introduced by impedance changes of the stimulated tissue and, in the near future, devices that deliver novel stimulation patterns with improved efficiency. Closed-loop adaptive IPGs are being tested, which may tailor stimulation to ongoing changes in the nervous system, reflected in biomarkers continuously recorded by the devices. Finer-grained DBS leads, in conjunction with new IPGs and advanced programming tools, may offer improved outcomes via current steering algorithms. Finally, even thermocoagulation-essentially replaced by DBS-is being advanced by new minimally-invasive approaches that may improve this therapy for selected patients in whom it may be preferred. Functional

  16. Technological advances in the surgical treatment of movement disorders.

    PubMed

    Gross, Robert E; McDougal, Margaret E

    2013-08-01

    Technological innovations have driven the advancement of the surgical treatment of movement disorders, from the invention of the stereotactic frame to the adaptation of deep brain stimulation (DBS). Along these lines, this review will describe recent advances in inserting neuromodulation modalities, including DBS, to the target, and in the delivery of therapy at the target. Recent radiological advances are altering the way that DBS leads are targeted and inserted, by refining the ability to visualize the subcortical targets using high-field strength magnetic resonance imaging and other innovations, such as diffusion tensor imaging, and the development of novel targeting devices enabling purely anatomical implantations without the need for neurophysiological monitoring. New portable computed tomography scanners also are facilitating lead implantation without monitoring, as well as improving radiological verification of DBS lead location. Advances in neurophysiological mapping include efforts to develop automatic target verification algorithms, and probabilistic maps to guide target selection. The delivery of therapy at the target is being improved by the development of the next generation of internal pulse generators (IPGs). These include constant current devices that mitigate the variability introduced by impedance changes of the stimulated tissue and, in the near future, devices that deliver novel stimulation patterns with improved efficiency. Closed-loop adaptive IPGs are being tested, which may tailor stimulation to ongoing changes in the nervous system, reflected in biomarkers continuously recorded by the devices. Finer-grained DBS leads, in conjunction with new IPGs and advanced programming tools, may offer improved outcomes via current steering algorithms. Finally, even thermocoagulation-essentially replaced by DBS-is being advanced by new minimally-invasive approaches that may improve this therapy for selected patients in whom it may be preferred. Functional

  17. Alcohol and Drug Treatment: How It Works, and How It Can Help You

    MedlinePlus

    Alcohol and Drug Treatment How It Works, And How It Can Help You With the Criminal Justice ... positive change. Why get treatment? Using drugs or alcohol may have contributed to your arrest or re- ...

  18. Nanotechnology-based intelligent drug design for cancer metastasis treatment.

    PubMed

    Gao, Yu; Xie, Jingjing; Chen, Haijun; Gu, Songen; Zhao, Rongli; Shao, Jingwei; Jia, Lee

    2014-01-01

    Traditional chemotherapy used today at clinics is mainly inherited from the thinking and designs made four decades ago when the Cancer War was declared. The potency of those chemotherapy drugs on in-vitro cancer cells is clearly demonstrated at even nanomolar levels. However, due to their non-specific effects in the body on normal tissues, these drugs cause toxicity, deteriorate patient's life quality, weaken the host immunosurveillance system, and result in an irreversible damage to human's own recovery power. Owing to their unique physical and biological properties, nanotechnology-based chemotherapies seem to have an ability to specifically and safely reach tumor foci with enhanced efficacy and low toxicity. Herein, we comprehensively examine the current nanotechnology-based pharmaceutical platforms and strategies for intelligent design of new nanomedicines based on targeted drug delivery system (TDDS) for cancer metastasis treatment, analyze the pros and cons of nanomedicines versus traditional chemotherapy, and evaluate the importance that nanomaterials can bring in to significantly improve cancer metastasis treatment.

  19. Pancreatic neuroendocrine tumors: clinical features, diagnosis and medical treatment: advances

    PubMed Central

    Ito, Tetsuhide; Igarashi, Hisato; Jensen, Robert T.

    2013-01-01

    Pancreatic neuroendocrine tumors (pNETs) comprise with gastrointestinal carcinoids, the main groups of gastrointestinal neuroendocrine tumors (GI-NETs). Although these two groups of GI-NETs share many features including histological aspects; over-/ectopic expression of somatostatin receptors; the ability to ectopically secrete hormones/peptides/amines which can result in distinct functional syndromes; similar approaches used for tumor localization and some aspects of treatment, it is now generally agreed they should be considered separate. They differ in their pathogenesis, hormonal syndromes produced, many aspects of biological behavior and most important, in their response to certain anti-tumor treatment (chemotherapy, molecular targeted therapies). In this chapter the clinical features of the different types of pNETs will be considered as well as aspects of their diagnosis and medical treatment of the hormone-excess state. Emphasis will be on controversial areas or recent advances. The other aspects of the management of these tumors (surgery, treatment of advanced disease, tumor localization) are not dealt with here, because they are covered in other chapters in this volume. PMID:23582916

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

    PubMed Central

    Polireddy, Kishore; Chen, Qi

    2016-01-01

    Pancreatic cancer is one of the most lethal cancers among all malignances, with a median overall survival of <1 year and a 5-year survival of ~5%. The dismal survival rate and prognosis are likely due to lack of early diagnosis, fulminant disease course, high metastasis rate, and disappointing treatment outcome. Pancreatic cancers harbor a variety of genetic alternations that render it difficult to treat even with targeted therapy. Recent studies revealed that pancreatic cancers are highly enriched with a cancer stem cell (CSC) population, which is resistant to chemotherapeutic drugs, and therefore escapes chemotherapy and promotes tumor recurrence. Cancer cell epithelial to mesenchymal transition (EMT) is highly associated with metastasis, generation of CSCs, and treatment resistance in pancreatic cancer. Reviewed here are the molecular biology of pancreatic cancer, the major signaling pathways regulating pancreatic cancer EMT and CSCs, and the advancement in current clinical and experimental treatments for pancreatic cancer. PMID:27471566

  1. Recent Advances in Diagnosis, Prevention, and Treatment of Human Respiratory Syncytial Virus

    PubMed Central

    Bawage, Swapnil Subhash; Tiwari, Pooja Munnilal; Singh, Shree Ram

    2013-01-01

    Human respiratory syncytial virus (RSV) is a common cause of respiratory infection in infants and the elderly, leading to significant morbidity and mortality. The interdisciplinary fields, especially biotechnology and nanotechnology, have facilitated the development of modern detection systems for RSV. Many anti-RSV compounds like fusion inhibitors and RNAi molecules have been successful in laboratory and clinical trials. But, currently, there are no effective drugs for RSV infection even after decades of research. Effective diagnosis can result in effective treatment, but the progress in both of these facets must be concurrent. The development in prevention and treatment measures for RSV is at appreciable pace, but the implementation into clinical practice still seems a challenge. This review attempts to present the promising diverse research approaches and advancements in the area of diagnosis, prevention, and treatment that contribute to RSV management. PMID:24382964

  2. Recent advances in lipid nanoparticle formulations with solid matrix for oral drug delivery.

    PubMed

    Das, Surajit; Chaudhury, Anumita

    2011-03-01

    Lipid nanoparticles based on solid matrix have emerged as potential drug carriers to improve gastrointestinal (GI) absorption and oral bioavailability of several drugs, especially lipophilic compounds. These formulations may also be used for sustained drug release. Solid lipid nanoparticle (SLN) and the newer generation lipid nanoparticle, nanostructured lipid carrier (NLC), have been studied for their capability as oral drug carriers. Biodegradable, biocompatible, and physiological lipids are generally used to prepare these nanoparticles. Hence, toxicity problems related with the polymeric nanoparticles can be minimized. Furthermore, stability of the formulations might increase than other liquid nano-carriers due to the solid matrix of these lipid nanoparticles. These nanoparticles can be produced by different formulation techniques. Scaling up of the production process from lab scale to industrial scale can be easily achieved. Reasonably high drug encapsulation efficiency of the nanoparticles was documented. Oral absorption and bioavailability of several drugs were improved after oral administration of the drug-loaded SLNs or NLCs. In this review, pros and cons, different formulation and characterization techniques, drug incorporation models, GI absorption and oral bioavailability enhancement mechanisms, stability and storage condition of the formulations, and recent advances in oral delivery of the lipid nanoparticles based on solid matrix will be discussed. PMID:21174180

  3. Behaviour therapy for obesity treatment considering approved drug therapy

    PubMed Central

    Kossmann, Beate; Ulle, Tanja; Kahl, Kai G.; Wasem, Jürgen; Aidelsburger, Pamela

    2008-01-01

    Introduction Obesity is a worldwide health problem whose prevalence is on the increase. Many obesity-associated diseases require intensive medical treatment and are the cause of a large proportion of health-related expenditures in Germany. Treatment of obesity includes nutritional, exercise and behaviour therapy, usually in combination. The goal of behaviour therapy for obesity is to bring about a long-term alteration in the eating and exercise habits of overweight and obese individuals. Under certain circumstances, drug treatment may be indicated. Objectives What is the effectiveness of behaviour therapy for obesity considering approved drugs reduce weight under medical, economic, ethical-social and legal aspects? Methods A systematic review was conducted using relevant electronic literature databases. Publications chosen according to predefined criteria are evaluated by approved methodical standards of the evidence-based medicine systematically and qualitatively. Results In total 18 studies, included one HTA and one meta-analysis could be identified according to the predefined inclusion criteria. Three studies compare behaviour therapy to other therapy forms (advice or instruction on nutritional changes, physical activity or a combination of the two), six studies evaluate different forms of behaviour therapy, four studies and four studies compare behaviour therapies mediated by Internet or telephone. Three studies could be identified examining the effect of the combination of behaviour and drug therapy. Furthermore one HTA and one meta-analysis could be included in the evaluation. The behaviour therapy in comparison with other therapy forms reveals a higher effectiveness. In comparison of the different therapeutic approaches of the behaviour therapy intensive behaviour therapy forms and group therapy show a higher effectiveness. Studies related to behaviour therapy based on media support demonstrate a weight reduction both through the interventions of media alone

  4. Advances in mechanisms, diagnosis, and treatment of pernicious anemia.

    PubMed

    Rojas Hernandez, Cristhiam M; Oo, Thein Hlaing

    2015-03-01

    Pernicious anemia (PA) is an entity initially described in 1849 as a condition that consisted of pallor, weakness, and progressive health decline. Since then several advances led to the conclusion that PA is an autoimmune disease characterized by the deficient absorption of dietary cobalamin. It is currently recognized as the most common cause of cobalamin deficiency worldwide. We hereby review the current understanding of the disease and its neurological, hematological, and biochemical manifestations with emphasis on the diagnostic approach, treatment, and monitoring strategies. We propose an algorithm for the diagnostic approach considering the current performance and limitations of the available diagnostic tools for evaluation of cobalamin status and the presence of autoimmune chronic atrophic gastritis (CAG). Patients with PA require lifelong treatment with cobalamin replacement therapy. The current widely available treatment can be provided through enteral or parenteral cobalamin supplements, with comparable efficacy and tolerability. PMID:25828519

  5. CAP--advancing the evaluation of preclinical Alzheimer disease treatments.

    PubMed

    Reiman, Eric M; Langbaum, Jessica B; Tariot, Pierre N; Lopera, Francisco; Bateman, Randall J; Morris, John C; Sperling, Reisa A; Aisen, Paul S; Roses, Allen D; Welsh-Bohmer, Kathleen A; Carrillo, Maria C; Weninger, Stacie

    2016-01-01

    If we are to find treatments to postpone, reduce the risk of, or completely prevent the clinical onset of Alzheimer disease (AD), we need faster methods to evaluate promising preclinical AD treatments, new ways to work together in support of common goals, and a determination to expedite the initiation and performance of preclinical AD trials. In this article, we note some of the current challenges, opportunities and emerging strategies in preclinical AD treatment. We describe the Collaboration for Alzheimer's Prevention (CAP)-a convening, harmonizing and consensus-building initiative to help stakeholders advance AD prevention research with rigour, care and maximal impact-and we demonstrate the impact of CAP on the goals and design of new preclinical AD trials.

  6. High-Intensity Focused Ultrasound Treatment for Advanced Pancreatic Cancer

    PubMed Central

    Zhou, Yufeng

    2014-01-01

    Pancreatic cancer is under high mortality but has few effective treatment modalities. High-intensity focused ultrasound (HIFU) is becoming an emerging approach of noninvasively ablating solid tumor in clinics. A variety of solid tumors have been tried on thousands of patients in the last fifteen years with great success. The principle, mechanism, and clinical outcome of HIFU were introduced first. All 3022 clinical cases of HIFU treatment for the advanced pancreatic cancer alone or in combination with chemotherapy or radiotherapy in 241 published papers were reviewed and summarized for its efficacy, pain relief, clinical benefit rate, survival, Karnofsky performance scale (KPS) score, changes in tumor size, occurrence of echogenicity, serum level, diagnostic assessment of outcome, and associated complications. Immune response induced by HIFU ablation may become an effective way of cancer treatment. Comments for a better outcome and current challenges of HIFU technology are also covered. PMID:25053938

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

    PubMed Central

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

    2015-01-01

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

  8. Managing Mental Health Problems in Everyday Life: Drug Treatment Client's Self-Care Strategies

    ERIC Educational Resources Information Center

    Holt, Martin; Treloar, Carla

    2008-01-01

    Little is understood about the self-care activities undertaken by drug treatment clients. Using data from a qualitative study of drug treatment and mental health we identify the self-care practices of drug treatment clients diagnosed with anxiety and depression. Seventy-seven participants were interviewed in four sites across Australia.…

  9. The Effectiveness of Drug Abuse Treatment: Implications for Controlling AIDS/HIV Infection. Background Paper 3.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Office of Technology Assessment.

    This background paper examines evidence for the effectiveness of treatment for drug abuse and evaluates the role of drug abuse treatment as a strategy to prevent Human Immunodeficiency Virus (HIV) spread. Because most intravenous (IV) drug users are not in treatment, the study also examines other approaches to HIV prevention. The remainder of the…

  10. And if the discovery of new drugs for the treatment of brain diseases depends on Asian countries?

    PubMed Central

    Kraus, Jean-Louis

    2014-01-01

    At the present time, developed countries are making a huge financial effort to support neuroscience research programs, particularly in the fields of advanced research and treatment of brain diseases and mental disorders. A part of this financial support is devoted to drug discovery programs. The purpose of this communication is to focus on the different parameters (economic, social, and scientific) allowing for the prominent belief that the discovery of new efficient drugs to treat brain disease to an increasing extent is likely to emanate from the Asian countries. A special focus on drug research and discovery in France reveals that, due to the current social context, the lack of small pharmaceutical ventures, the Mediator drug scandal, and the economic situation, the potential for discovering and developing new drugs is dramatically declining. PMID:27226835

  11. Development of an advanced water treatment system for wastewater reuse.

    PubMed

    Chung, H; Ku, B; Gregory, J

    2008-09-01

    The aim of this research was to develop an optimal reuse system applying various types of advanced oxidation processes such as titanium dioxide (TiO2), ozone (O3) and electro-coagulation/oxidation methods. This system is suitable for improving the treatment efficiency of difficult wastewaters, and for the efficient reuse of wastewater. The connecting systems were divided into various types to investigate the stability and treatment efficiency according to the kinds of waste load. Different treatment sequences were examined taking into consideration the characteristics and economical efficiency. In the case of electro-coagulation/oxidation + ozone system, the mean treatment efficiency in terms of BOD5, CODCr and SS removal was 98.7%. The effluent concentration was 50.2 mg l(-1), 38.3 mg l(-1), 30.4 mg l(-1), respectively. In considering the economical efficiency and commercial use, around an eighth of the treatment expenses and around a fifth of the maintenance expenses could be saved compared with existing water treatment systems. The initial construction expenses could be reduced by a third to a fifth. Therefore, if a proper implementation of this research is carried out in relation to site conditions and the purpose of the water reuse, the water reuse rate will be higher and water resources can be protected. PMID:18844120

  12. Development of an advanced water treatment system for wastewater reuse.

    PubMed

    Chung, H; Ku, B; Gregory, J

    2008-09-01

    The aim of this research was to develop an optimal reuse system applying various types of advanced oxidation processes such as titanium dioxide (TiO2), ozone (O3) and electro-coagulation/oxidation methods. This system is suitable for improving the treatment efficiency of difficult wastewaters, and for the efficient reuse of wastewater. The connecting systems were divided into various types to investigate the stability and treatment efficiency according to the kinds of waste load. Different treatment sequences were examined taking into consideration the characteristics and economical efficiency. In the case of electro-coagulation/oxidation + ozone system, the mean treatment efficiency in terms of BOD5, CODCr and SS removal was 98.7%. The effluent concentration was 50.2 mg l(-1), 38.3 mg l(-1), 30.4 mg l(-1), respectively. In considering the economical efficiency and commercial use, around an eighth of the treatment expenses and around a fifth of the maintenance expenses could be saved compared with existing water treatment systems. The initial construction expenses could be reduced by a third to a fifth. Therefore, if a proper implementation of this research is carried out in relation to site conditions and the purpose of the water reuse, the water reuse rate will be higher and water resources can be protected.

  13. Advances in Diagnosis and Treatment of Fetal Alcohol Spectrum Disorders

    PubMed Central

    Murawski, Nathen J.; Moore, Eileen M.; Thomas, Jennifer D.; Riley, Edward P.

    2015-01-01

    Prenatal alcohol exposure can cause a number of physical, behavioral, cognitive, and neural impairments, collectively known as fetal alcohol spectrum disorders (FASD). This article examines basic research that has been or could be translated into practical applications for the diagnosis or treatment of FASD. Diagnosing FASD continues to be a challenge, but advances are being made at both basic science and clinical levels. These include identification of biomarkers, recognition of subtle facial characteristics of exposure, and examination of the relation between face, brain, and behavior. Basic research also is pointing toward potential new interventions for FASD involving pharmacotherapies, nutritional therapies, and exercise interventions. Although researchers have assessed the majority of these treatments in animal models of FASD, a limited number of recent clinical studies exist. An assessment of this literature suggests that targeted interventions can improve some impairments resulting from developmental alcohol exposure. However, combining interventions may prove more efficacious. Ultimately, advances in basic and clinical sciences may translate to clinical care, improving both diagnosis and treatment. PMID:26259091

  14. Current and potential future drug treatments for osteoporosis.

    PubMed Central

    Patel, S

    1996-01-01

    There has been a major interest in the drug treatment of osteoporosis and an increase in the number of drugs available in most countries. The ideal drug (one which increases or restores bone density and trabecular connectivity) is still not available. However, in patients with relatively preserved trabecular connectivity and moderately reduced bone density, several agents have shown substantial clinical benefit. Oestrogens are still the mainstay of drug treatment, but the risks of breast cancer versus the cardiovascular and skeletal benefits with long term use have to be assessed in the individual. Newer tissue specific oestrogens show some promise in this respect. The bisphosphonates and possibly fluoride are likely to be the major alternatives to oestrogens in the medium term. The newer bisphosphonates, alendronate and in the future risedronate, are likely to supersede etidronate. Calcitriol probably has a limited role, confined to those patients in whom HRT or bisphosphonates are not appropriate. Calcium supplementation, or an increase in dietary intake if deficient, irrespective of which agent is used, is also of benefit. In older patients there is considerable support for using a combination of calcium and vitamin D. Whether combination treatment, for example oestrogens, bisphosphonates, and calcium together, will result in greater efficacy remains to be conclusively shown, but may be an attractive option in younger patients with higher bone turnover. Apart from fluoride, bone formation stimulators are unlikely to have a major role until the next century, although it may be possible to use growth factors as part of an ADFR regimen (A = activate remodelling, D = depress resorption, F = free formation, and R = repeat). This is still an important theoretical approach and needs further work with newer agents to see if increased efficacy can be found. In addition sequential treatment may be necessary in view of the limited time periods over which particular agents

  15. Multi-Target Directed Drugs: A Modern Approach for Design of New Drugs for the treatment of Alzheimer's Disease.

    PubMed

    Dias, Kris Simone Tranches; Viegas, Claudio

    2014-05-01

    Alzheimer's disease (AD) is a complex neurodegenerative disorder with a multi-faceted pathogenesis. So far, the therapeutic paradigm "one-compound-one-target" has failed and despite enormous efforts to elucidate the pathophysiology of AD, the disease is still incurable. The multiple factors involved in AD include amyloid aggregation to form insoluble neurotoxic plaques of Aβ, hyperphosphorylation of tau protein, oxidative stress, calcium imbalance, mitochondrial dysfunction and deterioration of synaptic transmission. These factors together, accentuate changes in the CNS homeostasis, starting a complex process of interconnected physiological damage, leading to cognitive and memory impairment and neuronal death. A recent approach for the rational design of new drug candidates, also called multitarget-directed ligand (MTDL) approach, has gained increasing attention by many research groups, which have developed a variety of hybrid compounds acting simultaneously on diverse biological targets. This review aims to show some recent advances and examples of the exploitation of MTDL approach in the rational design of novel drug candidate prototypes for the treatment of AD.

  16. Current and emerging options for the drug treatment of narcolepsy.

    PubMed

    De la Herrán-Arita, Alberto K; García-García, Fabio

    2013-11-01

    Narcolepsy/hypocretin deficiency (now called type 1 narcolepsy) is a lifelong neurologic disorder with well-established diagnostic criteria and etiology. Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness (EDS) and symptoms of dissociated rapid eye movement sleep such as cataplexy (sudden loss of muscle tone), hypnagogic hallucinations (sensory events that occur at the transition from wakefulness to sleep), sleep paralysis (inability to perform movements upon wakening or sleep onset), and nocturnal sleep disruption. As these symptoms are often disabling, most patients need life-long treatment. The treatment of narcolepsy is well defined, and, traditionally, amphetamine-like stimulants (i.e., dopaminergic release enhancers) have been used for clinical management to improve EDS and sleep attacks, whereas tricyclic antidepressants have been used as anticataplectics. However, treatments have evolved to better-tolerated compounds such as modafinil or armodafinil (for EDS) and adrenergic/serotonergic selective reuptake inhibitors (as anticataplectics). In addition, night-time administration of a short-acting sedative, c-hydroxybutyrate (sodium oxybate), has been used for the treatment for EDS and cataplexy. These therapies are almost always needed in combination with non-pharmacologic treatments (i.e., behavioral modification). A series of new drugs is currently being tested in animal models and in humans. These include a wide variety of hypocretin agonists, melanin- concentrating hormone receptor antagonists, antigenspecific immunopharmacology, and histamine H3 receptor antagonists/inverse agonists (e.g., pitolisant), which have been proposed for specific therapeutic applications, including the treatment of Alzheimer's disease, attention-deficit hyperactivity disorder, epilepsy, and more recently, narcolepsy. Even though current treatment is strictly symptomatic, based on the present state of knowledge of the pathophysiology of

  17. Current and emerging options for the drug treatment of narcolepsy.

    PubMed

    De la Herrán-Arita, Alberto K; García-García, Fabio

    2013-11-01

    Narcolepsy/hypocretin deficiency (now called type 1 narcolepsy) is a lifelong neurologic disorder with well-established diagnostic criteria and etiology. Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness (EDS) and symptoms of dissociated rapid eye movement sleep such as cataplexy (sudden loss of muscle tone), hypnagogic hallucinations (sensory events that occur at the transition from wakefulness to sleep), sleep paralysis (inability to perform movements upon wakening or sleep onset), and nocturnal sleep disruption. As these symptoms are often disabling, most patients need life-long treatment. The treatment of narcolepsy is well defined, and, traditionally, amphetamine-like stimulants (i.e., dopaminergic release enhancers) have been used for clinical management to improve EDS and sleep attacks, whereas tricyclic antidepressants have been used as anticataplectics. However, treatments have evolved to better-tolerated compounds such as modafinil or armodafinil (for EDS) and adrenergic/serotonergic selective reuptake inhibitors (as anticataplectics). In addition, night-time administration of a short-acting sedative, c-hydroxybutyrate (sodium oxybate), has been used for the treatment for EDS and cataplexy. These therapies are almost always needed in combination with non-pharmacologic treatments (i.e., behavioral modification). A series of new drugs is currently being tested in animal models and in humans. These include a wide variety of hypocretin agonists, melanin- concentrating hormone receptor antagonists, antigenspecific immunopharmacology, and histamine H3 receptor antagonists/inverse agonists (e.g., pitolisant), which have been proposed for specific therapeutic applications, including the treatment of Alzheimer's disease, attention-deficit hyperactivity disorder, epilepsy, and more recently, narcolepsy. Even though current treatment is strictly symptomatic, based on the present state of knowledge of the pathophysiology of

  18. Advances in Diagnosis and Treatments for Immune Thrombocytopenia

    PubMed Central

    Nomura, Shosaku

    2016-01-01

    Immune thrombocytopenia (ITP) is an acquired hemorrhagic condition characterized by the accelerated clearance of platelets caused by antiplatelet autoantibodies. A platelet count in peripheral blood <100 × 109/L is the most important criterion for the diagnosis of ITP. However, the platelet count is not the sole diagnostic criterion, and the diagnosis of ITP is dependent on additional findings. ITP can be classified into three types, namely, acute, subchronic, and persistent, based on disease duration. Conventional therapy includes corticosteroids, intravenous immunoglobulin, splenectomy, and watch-and-wait. Second-line treatments for ITP include immunosuppressive therapy [eg, anti-CD20 (rituximab)], with international guidelines, including rituximab as a second-line option. The most recently licensed drugs for ITP are the thrombopoietin receptor agonists (TRAs), such as romiplostim and eltrombopag. TRAs are associated with increased platelet counts and reductions in the number of bleeding events. TRAs are usually considered safe, effective treatments for patients with chronic ITP at risk of bleeding after failure of first-line therapies. Due to the high costs of TRAs, however, it is unclear if patients prefer these agents. In addition, some new agents are under development now. This manuscript summarizes the pathophysiology, diagnosis, and treatment of ITP. The goal of all treatment strategies for ITP is to achieve a platelet count that is associated with adequate hemostasis, rather than a normal platelet count. The decision to treat should be based on the bleeding severity, bleeding risk, activity level, likely side effects of treatment, and patient preferences. PMID:27441004

  19. Childhood Sexual Abuse Patterns, Psychosocial Correlates, and Treatment Outcomes among Adults in Drug Abuse Treatment

    ERIC Educational Resources Information Center

    Boles, Sharon M.; Joshi, Vandana; Grella, Christine; Wellisch, Jean

    2005-01-01

    This study reports on the effects of having a history of childhood sexual abuse (CSA) on treatment outcomes among substance abusing men and women (N = 2,434) in a national, multisite study of drug treatment outcomes. A history of CSA was reported by 27.2% of the women and 9.2% of the men. Controlling for gender, compared to patients without CSA,…

  20. Symptomatic treatment of multiple sclerosis using cannabinoids: recent advances.

    PubMed

    Smith, Paul F

    2007-09-01

    Recent years have seen a dramatic increase in the number of clinical trials investigating the potential efficacy of medicinal cannabinoids for the symptomatic treatment of chronic pain and spasticity in multiple sclerosis (MS). A number of different cannabinoids have been used, including: delta9-tetrahydrocannabinol (THC) itself; the synthetic delta9-THC, dronabinol; a 1:1 ratio of delta9-THC:cannabidiol (Sativex); and the synthetic delta9-THC metabolites CT-3 and nabilone. Other Cannabis extracts have also been tested. While 2-3 years ago there was little consensus in the literature, now the majority of studies are beginning to suggest that cannabinoids are useful in the treatment of MS in at least a subset of individuals. Their adverse side-effect profile has generally been mild compared with other drugs used for pain and spasticity; nonetheless, there is still concern about potential long-term side effects, particularly psychiatric side effects and effects on fetal development. PMID:17868014

  1. Neoadjuvant treatment for locally advanced rectal cancer: a systematic review.

    PubMed

    Uehara, Keisuke; Nagino, Masato

    2016-02-01

    We reviewed the history and the current status of neoadjuvant treatment for locally advanced rectal cancer (LARC) in Western countries and Japan. The introduction of total mesorectal excision (TME) and preoperative radiotherapy (RT) were treatment revolutions that resulted in improved local control after curative resection for rectal cancer. However, local relapses still occur, even in the era of TME, and remain a cause of recurrence worldwide. The high rate of distant metastasis after curative resection remains a problem. Furthermore, the introduction of newly developed cytotoxic agents into the LARC treatment strategy continues to be an ongoing challenge. Shifting part of an adjuvant chemotherapy (CTx) regimen to the preoperative period is a promising strategy. Currently, various novel methods, such as induction CTx, consolidation CTx, concomitant administration with RT, and neoadjuvant CTx without RT, have been attempted worldwide. Although some strategies have shown favorable short-term outcomes, the long-term efficacy of the treatments needs be evaluated. At the same time, we must investigate clinical and/or molecular biomarkers to predict the therapeutic effects of each treatment, which is the fastest route to providing ideal personalized therapy for patients with LARC.

  2. JCL roundtable: drug treatment of severe forms of familial hypercholesterolemia.

    PubMed

    Brown, W Virgil; Rader, Daniel J; Goldberg, Anne C

    2014-01-01

    Clinical lipidologists are often asked to manage patients with severely elevated low-density lipoprotein cholesterol (LDL-C) and other apolipoprotein B-containing lipoproteins. Statins at maximum doses and in combination with other drugs may not achieve adequate reductions in LDL-C in such patients. The most dramatic elevations are usually in patients with genetic abnormalities in the LDL receptor gene on both chromosome pairs. LDL-C values well in excess of 400 mg/dL are not fully responsive to current treatments. In the past few months, the Food and Drug Administration has approved 2 new drugs for special use in such patients; these are mipomersen and lomitapide. During the National Lipid Association's Scientific Sessions, 2 highly experienced clinician scientists who have completed research studies with these agents agreed to answer questions pertinent to the prescription use of these agents. These scientists are Dr Anne Goldberg from Washington University in St. Louis and Dr Daniel Rader from the University of Pennsylvania.

  3. Advances in methodology and current prospects for primary drug therapies for Alzheimer's disease.

    PubMed

    Knopman, D S

    2000-01-01

    There has been gratifying progress in the development of drugs for Alzheimer's disease (AD). Even though the current generation of medications, the cholinesterase inhibitors (CEIs), has produced only modest benefits, our concept of an "effective" therapy has matured considerably over this time. A less visible but equally important advance has been a quantum leap in expertise in clinical trial methodology. This chapter reviews the methodological underpinnings of clinical trials in AD: patient selection issues, key design issues, and an overview of currently available agents and the prospects for drugs of the future.

  4. Clozapine combined with different antipsychotic drugs for treatment resistant schizophrenia

    PubMed Central

    Cipriani, Andrea; Boso, Marianna; Barbui, Corrado

    2014-01-01

    Background Although clozapine has been shown to be the treatment of choice in people with schizophrenia that are resistant to treatment, one third to two thirds of people still have persistent positive symptoms despite clozapine monotherapy of adequate dosage and duration. The need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine is the most common reason for simultaneously prescribing a second antipsychotic drug in combination with clozapine. Objectives To determine the efficacy and tolerability of various clozapine combination strategies with antipsychotics in people with treatment resistant schizophrenia. Search methods We searched the Cochrane Schizophrenia Group Trials Register (March 2008) and MEDLINE (up to November 2008). We checked reference lists of all identified randomised controlled trials and requested pharmaceutical companies marketing investigational products to provide relevant published and unpublished data. Selection criteria We included only randomised controlled trials recruiting people of both sexes, aged 18 years or more, with a diagnosis of treatment-resistant schizophrenia (or related disorders) and comparing clozapine plus another antipsychotic drug with clozapine plus a different antipsychotic drug. Data collection and analysis Two review authors independently extracted data and resolved disagreement by discussion with third member of the team. When insufficient data were provided, we contacted the study authors. Main results Three small (range of number of participants 28 to 60) randomised controlled trials were included in the review. Even though results from individual studies did not find that one combination strategy is better than the others, the methodological quality of included studies was too low to allow authors to use the collected data to answer the research question correctly. Authors’ conclusions In this review we considered the risk of bias too high because of

  5. The urgent need for HIV and hepatitis prevention in drug treatment programs in Hungary

    PubMed Central

    Rácz, József; Neaigus, Alan; Ujhelyi, Eszter

    2008-01-01

    We assess HIV and hepatitis testing and counseling in drug treatment programs in Hungary, a country with low rates of HIV but high rates of HCV among injecting drug users. The official context of drug treatment programs is described, and, using key informants from representative drug treatment programs, the practice of HIV and hepatitis testing and counseling in such programs is assessed. While HIV testing and counseling occurs, testing and counseling for HBV and HCV are rare, especially in outpatient settings; and sexual risk in the drug use context is ineffectively addressed by treatment programs. Drug treatment centers are not adequately addressing the need to provide either HIV or hepatitis prevention services. There is an urgent need for preventing HIV and related infections among drug users by integrating HIV and hepatitis B and C prevention with drug treatment. PMID:15237056

  6. Antiepileptic drugs in the treatment of psychiatric disorders.

    PubMed

    Kaufman, Kenneth R

    2011-05-01

    The clinical interface between psychiatry and neurology is epilepsy; the pharmacological expression of this interface is antiepileptic drugs (AEDs), as they are used to treat both epilepsy and psychiatric disorders, especially bipolar disorders. The prevalence of psychiatric comorbidity and the risk of suicidal behavior/ideation/suicide are markedly increased in patients with epilepsy (PWE). Though AEDs receive initial indications for the treatment of epilepsy, currently the majority of AEDs are used to treat pain and psychiatric disorders. Thus in selecting the appropriate AEDs for treatment of PWE, consideration should be given to which AEDs best treat the epileptic disorder and the psychiatric comorbidity. This review is an overview of 21 AEDs in which negative psychotropic properties, approved indications in psychiatry, off-label studied uses in psychiatry, and principal uses in psychiatry are presented with literature review. A total of 40 psychiatric uses have been identified. Of the 21 AEDs reviewed, only 5 have U.S. Food and Drug Administration and/or European Medicines Agency psychiatric approval for limited uses; the majority of AEDs are used off-label. Many of these off-label uses are based on case reports, open-label studies, and poorly controlled or small-sample-size studies. In some instances, off-label use persists in the face of negative pivotal trials. Further placebo-controlled (augmentation and monotherapy) parallel-arm research with active comparators is required in the complex field of AED treatment of psychiatric disorders to minimize the treatment gap not only for PWE with psychiatric disorders, but also for psychiatric patients who would benefit from properly studied AEDs while minimizing adverse effects.

  7. Advances in the treatment of relapsing—remitting multiple sclerosis — critical appraisal of fingolimod

    PubMed Central

    Gasperini, Claudio; Ruggieri, Serena; Mancinelli, Chiara Rosa; Pozzilli, Carlo

    2013-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, traditionally considered to be an autoimmune, demyelinating disease. Based on this understanding, initial therapeutic strategies were directed at immune modulation and inflammation control. At present, there are five licensed first-line disease-modifying drugs for MS in Europe, and two second-line treatments. Currently available MS therapies have shown significant efficacy throughout many trials, but they produce different side effects. Despite disease-modifying drugs being well known and safe, they require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Therefore, the development of new therapeutic strategies is warranted. Several oral compounds are in late stages of development for treating MS. fingolimod is an oral sphingosine-1-phosphate receptor modulator that has demonstrated superior efficacy compared with placebo and interferon β-1a in phase III studies. It has already been approved in the treatment of MS. This review focuses on advances in current and novel oral treatment approaches in MS. We summarily review the oral compounds in this study, focusing on the recent development, approval, and the clinical experience with fingolimod. PMID:23483794

  8. New directions in cancer research 2003: technological advances in biology, drug resistance, and molecular pharmacology.

    PubMed

    Franks, Michael E; Macpherson, Gordon R; Lepper, Erin R; Figg, William D; Sparreboom, Alex

    2003-12-01

    The 94th Annual Meeting of the American Association for Cancer Research (AACR) was held from July 11 to 14, 2003 in Washington, DC, and provided an overview of the latest developments in the field of cancer. This report provides highlights of presentations on array-based and RNA-interference technologies to study cancer biology and molecular pharmacology of anticancer drugs, mechanisms and modulation of drug resistance patterns, recent developments in the treatment of prostate cancer, and the medicinal chemistry of established and novel anticancer drugs.

  9. Recent advancements of bortezomib in acute lymphocytic leukemia treatment.

    PubMed

    Du, Xiao-Li; Chen, Qi

    2013-01-01

    Although survival rates for acute lymphocytic leukemia (ALL), especially in children, have shown dramatic improvement over time, poor outcomes are still observed in patients who have refractory or relapsed disease after conventional chemotherapy. New therapeutic options are urgently needed. Bortezomib (Velcade, formerly PS-341) is the first proteasome inhibitor approved by the US FDA for the treatment of newly diagnosed multiple myeloma and relapsed/refractory multiple myeloma and mantle cell lymphoma. Although the mechanisms of bortezomib anticancer activity are still not completely understood, it is a new treatment option for patients with refractory or relapsed ALL, particularly when used in combination with conventional chemotherapy or targeted agents. This review summarizes recent advancements in the understanding of the bortezomib molecular mechanism of action in ALL. Understanding of the molecular approaches might help customize cancer chemotherapy for each individual patient, directing the field towards rational therapeutics.

  10. [Modern aspects of surgical treatment of locally advanced pelvic cancer].

    PubMed

    Solovyov, I A; Vasilchenko, M V; Lychev, A B; Ambartsumyan, S V; Alekseev, V V

    2015-09-01

    The aim of investigation is to improve surgical treatment of patients with locally advanced pelvic cancer. The basis of investigation is 186 patients with locally advanced pelvic cancer. The average age of patients is 65.2 ± 5.2 years (from 43.7 to 88.4 years). Among them are 112 women and 74 men. In the period from 2007 to 2015 they were carried out combined (101 patients) and expanded (85 patients) surgical intervention in the department of naval surgery of the Military medical academy after S.M.Kirov. Pelvic evisceration was performed in 63 cases. Both patients were performed isolated vascular hyperthermic chemical pelvic perfusion. Indications for plastic surgery of peritoneum pelvic were: total infralitoral pelvic evisceration (9 patients), dorsal infralitoral pelvic evisceration (11 cases) and expanded abdominoperineal rectum extirpation (34 patients). Plastic surgery with autogenouse tissues was performed to 43 patients, with reticulate explants--to 11 patients. The rate of postoperative complications was 40.2%. The rate of postoperative lethality was 8%. Expanded and combined operations of pelvic at patients with locally advanced cancer without absolute contra-indications can be performed irrespective of age. Plastic surgery of peritoneum pelvic after total and dorsal infralitoral pelvic evisceration and expanded abdominoperineal rectum extirpation indicated in all cases. The easiest method is plastic surgery with greater omentum or peritoneum pelvic. Plastic surgery with reticulate explants is performed when autoplastic is impossible. PMID:26827515

  11. Nursing Care in Alcohol and Drug User Treatment Facilities.

    PubMed

    Naegle, Madeline A

    2015-01-01

    Registered and advanced practice nurses are employed in substance user treatment facilities across the US and in most industrialized countries. Patterns of employment and job descriptions for nurses, however, are highly inconsistent and seriously flawed. Many regulatory system, legislative and government agency factors and to some degree, the nursing profession itself, sustain the flaws and limit the delivery of comprehensive care. Competencies linked to addictions nursing best practices are often underutilized because of narrow job descriptions. This results in limited health and nursing service delivery to vulnerable populations receiving treatment in these government funded programs. This article highlights the increasing demand for the delivery of integrated care to psychiatric and substance using populations. The author considers factors which stake holders can influence to change flawed employment patterns and limited access to comprehensive care for substance users.

  12. [Possibilities of non-drug treatment for Parkinson's disease].

    PubMed

    Pokhabov, D V; Abramov, V G; Pokhabov, D D

    2016-01-01

    In this article, non-drug methods of treatment of Parkinson's disease are reviewed. Particular attention is given to the motor symptoms of disease, specifically to gait disorders. Information about objective methods of gait impairment is presented. Own results that confirm the effect of a method of tempo-rhythmical correction of walk in patients with Parkinson's disease (PD) and vascular parkinsonism as well as a device for assessment of gait parameters developed by the authors are analyzed. The efficacy of other methods of gait correction using external cues, study design and level of evidence are analyzed as well. Information about possibilities of physical therapy and ergotherapy for correction of different symptoms of Parkinson's disease is presented. Positive and negative results of transcranial magnetic stimulation, light therapy and transcranial micropolarization in PD are analyzed. Basis non-drug methods of PD treatment, which currently have insufficient level of evidence (methods of mental relaxation and auditory training, methods of whole body vibration (vibromassage), laser therapy (photoacoustic therapy), acupuncture), are described in brief. Perspectives of the method of gait recovery in PD using tempo-rhythmic correction are emphasized.

  13. [Possibilities of non-drug treatment for Parkinson's disease].

    PubMed

    Pokhabov, D V; Abramov, V G; Pokhabov, D D

    2016-01-01

    In this article, non-drug methods of treatment of Parkinson's disease are reviewed. Particular attention is given to the motor symptoms of disease, specifically to gait disorders. Information about objective methods of gait impairment is presented. Own results that confirm the effect of a method of tempo-rhythmical correction of walk in patients with Parkinson's disease (PD) and vascular parkinsonism as well as a device for assessment of gait parameters developed by the authors are analyzed. The efficacy of other methods of gait correction using external cues, study design and level of evidence are analyzed as well. Information about possibilities of physical therapy and ergotherapy for correction of different symptoms of Parkinson's disease is presented. Positive and negative results of transcranial magnetic stimulation, light therapy and transcranial micropolarization in PD are analyzed. Basis non-drug methods of PD treatment, which currently have insufficient level of evidence (methods of mental relaxation and auditory training, methods of whole body vibration (vibromassage), laser therapy (photoacoustic therapy), acupuncture), are described in brief. Perspectives of the method of gait recovery in PD using tempo-rhythmic correction are emphasized. PMID:27635607

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

    PubMed Central

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

    2012-01-01

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

  15. Remembrance of conversations past: oral advance statements about medical treatment.

    PubMed Central

    Sommerville, A.

    1995-01-01

    Polls show increasing public interest in advance statements or directives about medical treatment ("living wills") but that few people, apart from Jehovah's Witnesses, carry such documents. Patients' firm, witnessed oral decisions are often sufficient to aid clinical decision making but should still be recorded in medical notes. Without documentation, dilemmas arise when others claim to know patients' views on the basis of past unrecorded conversations and demand withdrawal of treatment when patients are not terminally ill and cannot speak for themselves. Legal and ethical considerations oblige doctors to act in the best interests of an incapacitated patient; these considerations are now formally defined in draft legislation as including consideration of the patient's past wishes. The practicalities of ascertaining the strength and validity of such wishes from conversations reported second hand are complex. The paucity of legal and ethical guidance on reported oral advance statements makes debate imperative and renders the alternative of having designated surrogate decision makers increasingly attractive. Images p1664-a PMID:7795460

  16. Recovery among adolescents: models for post-treatment gains in drug abuse treatments.

    PubMed

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

    2014-03-01

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

  17. Glioblastoma multiforme: emerging treatments and stratification markers beyond new drugs

    PubMed Central

    Seidlitz, A; Kitzler, H H; Beuthien-Baumann, B; Krause, M

    2015-01-01

    Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults. The standard therapy for GBM is maximal surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide (TMZ). In spite of the extensive treatment, the disease is associated with poor clinical outcome. Further intensification of the standard treatment is limited by the infiltrating growth of the GBM in normal brain areas, the expected neurological toxicities with radiation doses >60 Gy and the dose-limiting toxicities induced by systemic therapy. To improve the outcome of patients with GBM, alternative treatment modalities which add low or no additional toxicities to the standard treatment are needed. Many Phase II trials on new chemotherapeutics or targeted drugs have indicated potential efficacy but failed to improve the overall or progression-free survival in Phase III clinical trials. In this review, we will discuss contemporary issues related to recent technical developments and new metabolic strategies for patients with GBM including MR (spectroscopy) imaging, (amino acid) positron emission tomography (PET), amino acid PET, surgery, radiogenomics, particle therapy, radioimmunotherapy and diets. PMID:26159214

  18. Glioblastoma multiforme: emerging treatments and stratification markers beyond new drugs.

    PubMed

    von Neubeck, C; Seidlitz, A; Kitzler, H H; Beuthien-Baumann, B; Krause, M

    2015-09-01

    Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults. The standard therapy for GBM is maximal surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide (TMZ). In spite of the extensive treatment, the disease is associated with poor clinical outcome. Further intensification of the standard treatment is limited by the infiltrating growth of the GBM in normal brain areas, the expected neurological toxicities with radiation doses >60 Gy and the dose-limiting toxicities induced by systemic therapy. To improve the outcome of patients with GBM, alternative treatment modalities which add low or no additional toxicities to the standard treatment are needed. Many Phase II trials on new chemotherapeutics or targeted drugs have indicated potential efficacy but failed to improve the overall or progression-free survival in Phase III clinical trials. In this review, we will discuss contemporary issues related to recent technical developments and new metabolic strategies for patients with GBM including MR (spectroscopy) imaging, (amino acid) positron emission tomography (PET), amino acid PET, surgery, radiogenomics, particle therapy, radioimmunotherapy and diets. PMID:26159214

  19. Treatment outcomes of micropulse transscleral cyclophotocoagulation in advanced glaucoma.

    PubMed

    Kuchar, Sarah; Moster, Marlene R; Reamer, Courtney B; Waisbourd, Michael

    2016-02-01

    Glaucoma is the leading cause of irreversible blindness worldwide. The goal of this study was to describe our experience with the novel micropulse transscleral cyclophotocoagulation (MP-TSCPC; IRIDEX IQ810 Laser Systems, CA) in patients with advanced glaucoma. Patients with advanced glaucoma who underwent MP-TSCPC were included in our study. Laser settings were 2000 mW of 810 nm infrared diode laser set on micropulse delivery mode. The laser was delivered over 360° for 100-240 s. The duty cycle was 31.3 %, which translated to 0.5 ms of "on time" and 1.1 ms of "off time." Surgical success was defined as an intraocular pressure (IOP) of 6-21 mmHg or a reduction of IOP by 20 % at the last follow-up visit. Failure was defined as an inability to meet the criteria for success or a need for incisional glaucoma surgery. Nineteen patients underwent MP-TSCPC with mean follow-up of 60.3 days. Mean IOP dropped from 37.9 mmHg preoperatively to 22.7 mmHg at last follow-up, representing a 40.1 % decrease. The success rate for initial treatment was 73.7 % (n = 14). Three patients underwent a second treatment, increasing the overall success rate to 89.5 % (n = 17). Four patients gained one line of vision, and four patients lost one line of vision. The novel MP-TSCPC laser had a high rate of surgical success after a short follow-up period in patients with advanced glaucoma. Further long-term evaluation and comparison to the traditional transscleral cyclophotocoagulation are warranted.

  20. Treatment outcomes of micropulse transscleral cyclophotocoagulation in advanced glaucoma.

    PubMed

    Kuchar, Sarah; Moster, Marlene R; Reamer, Courtney B; Waisbourd, Michael

    2016-02-01

    Glaucoma is the leading cause of irreversible blindness worldwide. The goal of this study was to describe our experience with the novel micropulse transscleral cyclophotocoagulation (MP-TSCPC; IRIDEX IQ810 Laser Systems, CA) in patients with advanced glaucoma. Patients with advanced glaucoma who underwent MP-TSCPC were included in our study. Laser settings were 2000 mW of 810 nm infrared diode laser set on micropulse delivery mode. The laser was delivered over 360° for 100-240 s. The duty cycle was 31.3 %, which translated to 0.5 ms of "on time" and 1.1 ms of "off time." Surgical success was defined as an intraocular pressure (IOP) of 6-21 mmHg or a reduction of IOP by 20 % at the last follow-up visit. Failure was defined as an inability to meet the criteria for success or a need for incisional glaucoma surgery. Nineteen patients underwent MP-TSCPC with mean follow-up of 60.3 days. Mean IOP dropped from 37.9 mmHg preoperatively to 22.7 mmHg at last follow-up, representing a 40.1 % decrease. The success rate for initial treatment was 73.7 % (n = 14). Three patients underwent a second treatment, increasing the overall success rate to 89.5 % (n = 17). Four patients gained one line of vision, and four patients lost one line of vision. The novel MP-TSCPC laser had a high rate of surgical success after a short follow-up period in patients with advanced glaucoma. Further long-term evaluation and comparison to the traditional transscleral cyclophotocoagulation are warranted. PMID:26714976

  1. ANALYSIS ON EFFLUENT WATER QUALITY AND ELECTRICITY CONSUMPTION AFTER INTRODUCING ADVANCED SEWAGE TREATMENT

    NASA Astrophysics Data System (ADS)

    Shiojiri, Yasuo; Maekawa, Shunich

    We analyze effluent water quality and electricity consumption after in troducing advanced treatment in sewage treatment plant. We define 'advanced treatment ratio' as volume of treated water through advanced treatment processes divided by total volume of treated water in plant. Advanced treatment ratio represents degree of introducing advanced treatment. We build two types of equation. One represents relation between effluent water quality and advanced treatment ratio, the other between electricity consumption and advanced treatment ratio. Each equation is fitted by least squares on 808 samples: 8 fiscal years operation data of 101 plants working in Kanagawa, Tokyo, Saitama and Chiba areas, and coefficient of advanced treatment ratio is estimated. The result is as follows. (1) After introducing advanced treatment aimed at nitrogen removal, T-N in effluent water decreases by 51.3% and electricity consum ption increases by 52.2%. (2) After introducing advanced treatment aimed at phosphorus removal, T-P in effluent water decreases by 27.8%. Using the above result, we try prioritizing 71 plants in Tokyo Bay watershed about raising advanced treatment ratio, so that, in total, pollutant in effluent water decreases with minimized increase of electricity consumption.

  2. The Efficacy of Coerced Treatment for Offenders: An Evaluation of Two Residential Forensic Drug and Alcohol Treatment Programs.

    ERIC Educational Resources Information Center

    Baird, Francis X.; Frankel, Arthur J.

    2001-01-01

    Reviews the history of community-based treatment for offenders with drug and alcohol addiction. Describes the treatment regimen in two residential programs for offenders with drug and alcohol problems, including a description of the components of the residential treatment model utilized in these two programs. Findings support the efficacy of…

  3. Role of excipients and polymeric advancements in preparation of floating drug delivery systems

    PubMed Central

    Kaushik, Avinash Y; Tiwari, Ajay K; Gaur, Ajay

    2015-01-01

    Since decade or two, the development of floating drug delivery systems becomes a significant and novel tool as having low density than gastric content. There are various advanced polymers including chitosan, eudragit, etc., and excipients such as; pore forming agent, surfactants, etc. All of them are discussed briefly, and results are concluded from various reputed researches. We have discussed all natural and synthetic systems with their effect on the release and other parameters which are essential for the floating formulation development. PMID:25599027

  4. The role of big data and advanced analytics in drug discovery, development, and commercialization.

    PubMed

    Szlezák, N; Evers, M; Wang, J; Pérez, L

    2014-05-01

    In recent years, few ideas have captured the imagination of health-care practitioners as much as the advent of "big data" and the advanced analytical methods and technologies used to interpret it-it is a trend seen as having the potential to revolutionize biology, medicine, and health care.(1,2,3) As new types of data and tools become available, a unique opportunity is emerging for smarter and more effective discovery, development, and commercialization of innovative biopharmaceutical drugs.

  5. Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment

    PubMed Central

    Tzvetkov, Mladen V.

    2008-01-01

    Variation in the human genome is a most important cause of variable response to drugs and other xenobiotics. Susceptibility to almost all diseases is determined to some extent by genetic variation. Driven by the advances in molecular biology, pharmacogenetics has evolved within the past 40 years from a niche discipline to a major driving force of clinical pharmacology, and it is currently one of the most actively pursued disciplines in applied biomedical research in general. Nowadays we can assess more than 1,000,000 polymorphisms or the expression of more than 25,000 genes in each participant of a clinical study – at affordable costs. This has not yet significantly changed common therapeutic practices, but a number of physicians are starting to consider polymorphisms, such as those in CYP2C9, CYP2C19, CYP2D6, TPMT and VKORC1, in daily medical practice. More obviously, pharmacogenetics has changed the practices and requirements in preclinical and clinical drug research; large clinical trials without a pharmacogenomic add-on appear to have become the minority. This review is about how the discipline of pharmacogenetics has evolved from the analysis of single proteins to current approaches involving the broad analyses of the entire genome and of all mRNA species or all metabolites and other approaches aimed at trying to understand the entire biological system. Pharmacogenetics and genomics are becoming substantially integrated fields of the profession of clinical pharmacology, and education in the relevant methods, knowledge and concepts form an indispensable part of the clinical pharmacology curriculum and the professional life of pharmacologists from early drug discovery to pharmacovigilance. PMID:18224312

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

    PubMed Central

    2015-01-01

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

  7. Advances in Risk Classification and Treatment Strategies for Neuroblastoma.

    PubMed

    Pinto, Navin R; Applebaum, Mark A; Volchenboum, Samuel L; Matthay, Katherine K; London, Wendy B; Ambros, Peter F; Nakagawara, Akira; Berthold, Frank; Schleiermacher, Gudrun; Park, Julie R; Valteau-Couanet, Dominique; Pearson, Andrew D J; Cohn, Susan L

    2015-09-20

    Risk-based treatment approaches for neuroblastoma have been ongoing for decades. However, the criteria used to define risk in various institutional and cooperative groups were disparate, limiting the ability to compare clinical trial results. To mitigate this problem and enhance collaborative research, homogenous pretreatment patient cohorts have been defined by the International Neuroblastoma Risk Group classification system. During the past 30 years, increasingly intensive, multimodality approaches have been developed to treat patients who are classified as high risk, whereas patients with low- or intermediate-risk neuroblastoma have received reduced therapy. This treatment approach has resulted in improved outcome, although survival for high-risk patients remains poor, emphasizing the need for more effective treatments. Increased knowledge regarding the biology and genetic basis of neuroblastoma has led to the discovery of druggable targets and promising, new therapeutic approaches. Collaborative efforts of institutions and international cooperative groups have led to advances in our understanding of neuroblastoma biology, refinements in risk classification, and stratified treatment strategies, resulting in improved outcome. International collaboration will be even more critical when evaluating therapies designed to treat small cohorts of patients with rare actionable mutations. PMID:26304901

  8. Advances in Risk Classification and Treatment Strategies for Neuroblastoma

    PubMed Central

    Pinto, Navin R.; Applebaum, Mark A.; Volchenboum, Samuel L.; Matthay, Katherine K.; London, Wendy B.; Ambros, Peter F.; Nakagawara, Akira; Berthold, Frank; Schleiermacher, Gudrun; Park, Julie R.; Valteau-Couanet, Dominique; Pearson, Andrew D.J.

    2015-01-01

    Risk-based treatment approaches for neuroblastoma have been ongoing for decades. However, the criteria used to define risk in various institutional and cooperative groups were disparate, limiting the ability to compare clinical trial results. To mitigate this problem and enhance collaborative research, homogenous pretreatment patient cohorts have been defined by the International Neuroblastoma Risk Group classification system. During the past 30 years, increasingly intensive, multimodality approaches have been developed to treat patients who are classified as high risk, whereas patients with low- or intermediate-risk neuroblastoma have received reduced therapy. This treatment approach has resulted in improved outcome, although survival for high-risk patients remains poor, emphasizing the need for more effective treatments. Increased knowledge regarding the biology and genetic basis of neuroblastoma has led to the discovery of druggable targets and promising, new therapeutic approaches. Collaborative efforts of institutions and international cooperative groups have led to advances in our understanding of neuroblastoma biology, refinements in risk classification, and stratified treatment strategies, resulting in improved outcome. International collaboration will be even more critical when evaluating therapies designed to treat small cohorts of patients with rare actionable mutations. PMID:26304901

  9. Advances in the topical treatment of diabetic foot ulcers.

    PubMed

    Papanas, N; Eleftheriadou, I; Tentolouris, N; Maltezos, E

    2012-05-01

    The diabetic foot remains a major cause of morbidity worldwide. Even though considerable progress has been achieved over the past years, there is still an urgent need for improvement. While established therapeutic modalities (revascularization, casting and debridement) remain the mainstay of management, there is, therefore, continuous development of new treatment options. This review provides an outlook of advances in topical treatment, including bioengineered skin substitutes (such as Dermagraft, Apligraf, HYAFF, OASIS and Graftjacket), extracellular matrix proteins (such as Hyalofill and E-matrix), as well as miscellaneous further therapeutic adjuncts. Although promising, new therapies should not, for the time being, constitute the basis of management, since clinical experience has not yet confirmed their effectiveness in hard-to-heal diabetic foot ulcers. Furthermore, their cost-effectiveness merits further investigation. Instead, they should only be considered in combination with established treatments or be attempted when these have not been successful. Moreover, we should not be oblivious to the fact that established and emerging treatments need to be practised in the setting of multidisciplinary foot clinics to reduce the number of amputations.

  10. Advances in Risk Classification and Treatment Strategies for Neuroblastoma.

    PubMed

    Pinto, Navin R; Applebaum, Mark A; Volchenboum, Samuel L; Matthay, Katherine K; London, Wendy B; Ambros, Peter F; Nakagawara, Akira; Berthold, Frank; Schleiermacher, Gudrun; Park, Julie R; Valteau-Couanet, Dominique; Pearson, Andrew D J; Cohn, Susan L

    2015-09-20

    Risk-based treatment approaches for neuroblastoma have been ongoing for decades. However, the criteria used to define risk in various institutional and cooperative groups were disparate, limiting the ability to compare clinical trial results. To mitigate this problem and enhance collaborative research, homogenous pretreatment patient cohorts have been defined by the International Neuroblastoma Risk Group classification system. During the past 30 years, increasingly intensive, multimodality approaches have been developed to treat patients who are classified as high risk, whereas patients with low- or intermediate-risk neuroblastoma have received reduced therapy. This treatment approach has resulted in improved outcome, although survival for high-risk patients remains poor, emphasizing the need for more effective treatments. Increased knowledge regarding the biology and genetic basis of neuroblastoma has led to the discovery of druggable targets and promising, new therapeutic approaches. Collaborative efforts of institutions and international cooperative groups have led to advances in our understanding of neuroblastoma biology, refinements in risk classification, and stratified treatment strategies, resulting in improved outcome. International collaboration will be even more critical when evaluating therapies designed to treat small cohorts of patients with rare actionable mutations.

  11. Vismodegib: A smoothened inhibitor for the treatment of advanced basal cell carcinoma.

    PubMed

    Aditya, Suruchi; Rattan, Aditya

    2013-10-01

    Incidence of basal cell carcinoma (BCC), the most common skin cancer in humans, is rising. Surgery is the mainstay of treatment but there is no standard of care for locally advanced or metastatic disease. Hedgehog signaling proteins are critical for cell growth and differentiation during embryogenesis; Hh pathway is silenced in adults. Dysregulated or aberrant Hh signaling has been implicated in the pathogenesis of BCC. This hyperactive pathway can be inhibited by use of smoothened inhibitors such as vismodegib. Food and drug administration approved this oral, once-daily medication in 2012 to treat adults with metastatic BCC or locally advanced, recurrent BCC after surgery and also for patients with locally advanced BCC who are not candidates for surgery or radiation treatment. Clinical studies have shown it to be highly efficacious and the most common adverse effects include, muscle spasms, alopecia and dysgeusia. Use of targeted biologic modifiers, exemplified by Hh directed therapeutics offer a new hope to patients with high-surgical morbidity or inoperable tumors.

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

    PubMed Central

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

    2014-01-01

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

  13. Recent advances in the surgical treatment of hepatocellular carcinoma.

    PubMed

    Morise, Zenichi; Kawabe, Norihiko; Tomishige, Hirokazu; Nagata, Hidetoshi; Kawase, Jin; Arakawa, Satoshi; Yoshida, Rie; Isetani, Masashi

    2014-10-21

    Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The treatment of HCC is complex and complicated by the severity of associated chronic liver disease, the stage of HCC, and the clinical condition of the patient. Liver resection (LR) is one of the most efficient treatments for patients with HCC, with an expected 5-year survival of 38%-61% depending on the stage of the disease. Improved liver function assessment, increased understanding of segmental liver anatomy from advanced imaging studies, and surgical technical progress are important factors that have led to reduced mortality in patients with HCC. The indication for LR may be expanded due to emerging evidences from laparoscopic hepatectomies and combined treatments with newly developed chemotherapies. Liver transplantation (LT) is considered as an ideal treatment for removal of existing tumors and the injured/preneoplastic underlying liver tissue with impaired liver function and the risk of multicentric carcinogenesis that results from chronically injured liver. However, LT is restricted to patients with minimal risk of tumor recurrence under immunosuppression. The expansion of criteria for LT in HCC patients is still under trial and discussion. Limited availability of grafts, as well as the risk and the cost of transplantation have led to considerable interest in expansion of the donor pool, living donor-related transplantation, and combined treatment involving LR and LT. This highlight presents evidence concerning recent studies evaluating LR and LT in HCC patients. In addition, alternative therapies for the treatment of early stage tumors and the management of patients on transplant waiting lists are discussed. PMID:25339825

  14. Drug-conjugated antibodies for the treatment of cancer

    PubMed Central

    Lambert, John M

    2013-01-01

    Despite considerable effort, application of monoclonal antibody technology has had only modest success in improving treatment outcomes in patients with solid tumours. Enhancing the cancer cell-killing activity of antibodies through conjugation to highly potent cytotoxic ‘payloads’ to create antibody–drug conjuates (ADCs) offers a strategy for developing anti-cancer drugs of great promise. Early ADCs exhibited side-effect profiles similar to those of ‘classical’ chemotherapeutic agents and their performance in clinical trials in cancer patients was generally poor. However, the recent clinical development of ADCs that have highly potent tubulin-acting agents as their payloads have profoundly changed the outlook for ADC technology. Twenty-five such ADCs are in clinical development and one, brentuximab vedotin, was approved by the FDA in August, 2011, for the treatment of patients with Hodgkin's lymphoma and patients with anaplastic large cell lymphoma, based on a high rate of durable responses in single arm phase II clinical trials. More recently, a second ADC, trastuzumab emtansine, has shown excellent anti-tumour activity with the presentation of results of a 991-patient randomized phase III trial in patients with HER2-positive metastatic breast cancer. Treatment with this ADC (single agent) resulted in a significantly improved progression-free survival of 9.6 months compared with 6.4 months for lapatinib plus capecitabine in the comparator arm and significantly prolonged overall survival. Besides demonstrating excellent efficacy, these ADCs were remarkably well tolerated. Thus these, and other ADCs in development, promise to achieve the long sought goal of ADC technology, that is, of having compounds with high anti-tumour activity at doses where adverse effects are generally mild. PMID:23173552

  15. Drug utilization of clarithromycin for gastrointestinal disease treatment

    PubMed Central

    Zhou, Quan; Zhu, Ling-Ling; Yan, Xiao-Feng; Pan, Wen-Sheng; Zeng, Su

    2008-01-01

    AIM: To evaluate the patterns of use of clarithromycin for gastrointestinal disease treatment and promote its rational use. METHODS: Using a structured pro forma, we conducted a two-month survey of the electronic prescriptions containing immediate-release (IR) or sustained-release (SR) product of clarithromycin for outpatients with gastrointestinal diseases in a 2200-bed general hospital. Suitability of the prescription was audited retrospectively. RESULTS: One hundred and sixty-four prescriptions of SR product and 110 prescriptions of IR product were prescribed for gastrointestinal disease treatment. Among prescriptions for anti-Helicobacter pylori (H pylori) therapy, triple therapy take the dominant position (91.8%), followed by quadruple therapy (4.3%) and dual therapy (3.9%). Amoxicillin was the most frequently co-prescribed antibiotic. Furazolidone and levofloxacin are used more widely than metronidazole or tinidazole. Clarithromycin SR was administered at inappropriate time points in all prescriptions. Fifty percent of all prescriptions of clarithromycin SR, and 6.4% of prescriptions of clarithromycin IR, were prescribed at inappropriate dosing intervals. Surprisingly, disconcordance between diagnoses and indications was observed in all prescriptions of clarithromycin SR which has not been approved for treating H pylori infection although off-label use for this purpose was reported in literature. On the contrary, only one prescription (0.9%) of clarithromycin IR was prescribed for unapproved indication (i.e. gastro-oesophageal reflux disease). 1.4% of prescriptions for chronic gastritis or peptic ulcer treatment were irrational in that clarithromycin was not co-prescribed with gastric acid inhibitors. Clinical significant CYP3A based drug interactions with clarithromycin were identified. CONCLUSION: There is a great scope to improve the quality of clarithromycin prescribing in patients with gastrointestinal disease, especially with regard to administration

  16. A latent class analysis of external barriers to drug treatment in China.

    PubMed

    Qi, Chang; Kelly, Brian C; Liu, Tieqiao; Liao, Yanhui; Hao, Wei; Wang, Jichuan

    2013-10-01

    Drug treatment services of varying types have been scaled up in China over the past decade. Yet, barriers to treatment remain among the population of drug users in China. In this paper, we use a person-centered approach to examine external barriers to drug treatment among a sample of Chinese drug users. Specifically, we used a latent class analysis to determine a typology of external barriers to treatment among a sample of 262 drug users. The results of the analyses suggest three-classes of drug users with respect to their perceptions of external barriers to treatment--Major Barriers, Low Barriers, and Systems-level Barriers--indicating that drug users are a heterogeneous population on this matter. Age and types of drugs used were predictors of class membership. In this regard, different tactics must be utilized in order to successfully reach this wide ranging group of individuals. PMID:23827260

  17. A latent class analysis of external barriers to drug treatment in China

    PubMed Central

    Qi, Chang; Kelly, Brian C; Liu, Tieqiao; Liao, Yanhui; Hao, Wei; Wang, Jichuan

    2013-01-01

    Drug treatment services of varying types have been scaled up in China over the past decade. Yet, barriers to treatment remain among the population of drug users in China. In this paper, we use a person-centered approach to examine external barriers to drug treatment among a sample of Chinese drug users. Specifically, we used a latent class analysis to determine a typology of external barriers to treatment among a sample of 262 drug users. The results of the analyses suggest three-classes of drug users with respect to their perceptions of external barriers to treatment – Major Barriers, Low Barriers, and Systems-level Barriers – indicating that drug users are a heterogeneous population on this matter. Age and types of drugs used were predictors of class membership. In this regard, different tactics must be utilized in order to successfully reach this wide ranging group of individuals. PMID:23827260

  18. Application of hot melt extrusion for poorly water-soluble drugs: limitations, advances and future prospects.

    PubMed

    Lu, Ming; Guo, Zhefei; Li, Yongcheng; Pang, Huishi; Lin, Ling; Liu, Xu; Pan, Xin; Wu, Chuanbin

    2014-01-01

    Hot melt extrusion (HME) is a powerful technology to enhance the solubility and bioavailability of poorly water-soluble drugs by producing amorphous solid dispersions. Although the number of articles and patents about HME increased dramatically in the past twenty years, there are very few commercial products by far. The three main obstacles limiting the commercial application of HME are summarized as thermal degradation of heat-sensitive drugs at high process temperature, recrystallization of amorphous drugs during storage and dissolving process, and difficulty to obtain products with reproducible physicochemical properties. Many efforts have been taken in recent years to understand the basic mechanism underlying these obstacles and then to overcome them. This article reviewed and summarized the limitations, recent advances, and future prospects of HME. PMID:23651401

  19. Training the Staff of a Drug Addiction Treatment Facility: A Case Study of Hogar De Encuentro

    ERIC Educational Resources Information Center

    Sorensen, Andrew A.; Leske, M. Cristina

    1977-01-01

    This paper, presented at the American Public Health Association meeting; Chicago, November 1975, discusses a staff training program at a drug addiction treatment facility established for Spanish-speaking (and other) drug addicts. Staff improved counseling skills and knowledge of drug addiction, but changed little in attitudes toward drug use and…

  20. Advances in Diagnosis and Treatments for Immune Thrombocytopenia.

    PubMed

    Nomura, Shosaku

    2016-01-01

    Immune thrombocytopenia (ITP) is an acquired hemorrhagic condition characterized by the accelerated clearance of platelets caused by antiplatelet autoantibodies. A platelet count in peripheral blood <100 × 10(9)/L is the most important criterion for the diagnosis of ITP. However, the platelet count is not the sole diagnostic criterion, and the diagnosis of ITP is dependent on additional findings. ITP can be classified into three types, namely, acute, subchronic, and persistent, based on disease duration. Conventional therapy includes corticosteroids, intravenous immunoglobulin, splenectomy, and watch-and-wait. Second-line treatments for ITP include immunosuppressive therapy [eg, anti-CD20 (rituximab)], with international guidelines, including rituximab as a second-line option. The most recently licensed drugs for ITP are the thrombopoietin receptor agonists (TRAs), such as romiplostim and eltrombopag. TRAs are associated with increased platelet counts and reductions in the number of bleeding events. TRAs are usually considered safe, effective treatments for patients with chronic ITP at risk of bleeding after failure of first-line therapies. Due to the high costs of TRAs, however, it is unclear if patients prefer these agents. In addition, some new agents are under development now. This manuscript summarizes the pathophysiology, diagnosis, and treatment of ITP. The goal of all treatment strategies for ITP is to achieve a platelet count that is associated with adequate hemostasis, rather than a normal platelet count. The decision to treat should be based on the bleeding severity, bleeding risk, activity level, likely side effects of treatment, and patient preferences. PMID:27441004

  1. Advances in the treatment of cutaneous lupus erythematosus.

    PubMed

    Kuhn, A; Landmann, A; Wenzel, J

    2016-07-01

    Lupus erythematosus (LE) is a multifactorial autoimmune disease with clinical manifestations of differing severity which may present with skin manifestations as primary sign of the disease (cutaneous lupus erythematosus, CLE) or as part of a disease spectrum (systemic lupus erythematosus, SLE). To date, no drugs are approved specifically for the treatment of CLE and only single agents have been applied in randomized controlled trials. Therefore, topical and systemic agents are used "off-label", primarily based on open-label studies, case series, retrospective analyses, and expert opinions. In contrast, several agents, such as hydroxychloroquine, chloroquine, cyclophosphamide, azathioprine, and belimumab, are approved for the treatment of SLE. Recent approaches in the understanding of the molecular pathogenesis of LE enabled the development of further new agents, which target molecules such as interleukin 6 (IL-6) and interferon (IFN). Only single trials, however, applied these new agents in patients with cutaneous involvement of the disease and/or included endpoints which evaluated the efficacy of these agents on skin manifestations. This article provides an updated review on new and recent approaches in the treatment of CLE. PMID:27252259

  2. Advances in the treatment of cutaneous lupus erythematosus.

    PubMed

    Kuhn, A; Landmann, A; Wenzel, J

    2016-07-01

    Lupus erythematosus (LE) is a multifactorial autoimmune disease with clinical manifestations of differing severity which may present with skin manifestations as primary sign of the disease (cutaneous lupus erythematosus, CLE) or as part of a disease spectrum (systemic lupus erythematosus, SLE). To date, no drugs are approved specifically for the treatment of CLE and only single agents have been applied in randomized controlled trials. Therefore, topical and systemic agents are used "off-label", primarily based on open-label studies, case series, retrospective analyses, and expert opinions. In contrast, several agents, such as hydroxychloroquine, chloroquine, cyclophosphamide, azathioprine, and belimumab, are approved for the treatment of SLE. Recent approaches in the understanding of the molecular pathogenesis of LE enabled the development of further new agents, which target molecules such as interleukin 6 (IL-6) and interferon (IFN). Only single trials, however, applied these new agents in patients with cutaneous involvement of the disease and/or included endpoints which evaluated the efficacy of these agents on skin manifestations. This article provides an updated review on new and recent approaches in the treatment of CLE.

  3. Targeted treatments in advanced renal cell carcinoma: focus on axitinib

    PubMed Central

    Verzoni, Elena; Grassi, Paolo; Testa, Isabella; Iacovelli, Roberto; Biondani, Pamela; Garanzini, Enrico; De Braud, Filippo; Procopio, Giuseppe

    2014-01-01

    Antiangiogenesis options have evolved rapidly in the last few years, with an increasing number of agents currently approved by the US Food and Drug Administration and European Medicines Agency. Angiogenesis inhibitors have been shown to be very effective for the treatment of metastatic renal cancer cell. Axitinib is a third-generation inhibitor of vascular endothelial growth factor receptor and is currently being developed for the treatment of various malignancies. The pharmacokinetic properties of axitinib may have a selective therapeutic effect, with minimal adverse reactions and enhanced safety. In a large Phase III study of previously treated patients with metastatic renal cell carcinoma, axitinib achieved a longer progression-free survival than sorafenib with an acceptable safety profile and good quality of life. This review focuses on the pharmacology, pharmacokinetics, and clinical activity of axitinib in the current treatment of renal cell carcinoma. The role of axitinib in the adjuvant and/or neoadjuvant setting needs to be evaluated in further clinical trials. PMID:24715765

  4. Treatment of childhood hypophosphatasia with nonsteroidal antiinflammatory drugs.

    PubMed

    Girschick, H J; Seyberth, H W; Huppertz, H I

    1999-11-01

    Hypophosphatasia (HP) is an inborn error of metabolism that is characterized by reduced bone mineralization. The aim of this investigation was to evaluate treatment of incapacitating lower limb pain in patients with childhood HP using nonsteroidal antiinflammatory drugs (NSAID). All patients (seven boys; age 32 months to 16 years) presented with delayed walking, the typical waddling gait, muscular weakness of the lower limbs, and a limited walking distance. Six patients had severe diffuse lower limb pain following physical activity and were therefore treated with NSAID. The benefit of this treatment was evaluated clinically and by measurement of renally (PGE2) and systemically (PGE-M) derived prostaglandins (PG) in urine before and during therapy. After treatment with NSAID all six patients showed marked clinical improvement with reduced pain, increased muscle strength, and a normalized walking distance. Levels of PGE-M, which had been elevated in four patients prior to therapy, returned to normal. The use of NSAID in childhood HP should be considered as a possible therapeutic approach because the quality of life in these patients is markedly impaired by pain of the limbs. Elevated PG might play a role in the bone metabolism of HP patients. PMID:10574582

  5. Current drugs for the treatment of dry cough.

    PubMed

    Padma, L

    2013-05-01

    Cough is one of the commonest symptoms of respiratory tract infections and is a frequent problem encountered in general practice as well as in hospital practice. A wide range of disease processes may present with cough and definitive treatment depends on identifying the cause and diagnosis. Specific treatment of the cause should control the cough, but this may not occur in all cases and in a sizeable proportion of patients, no associated cause can be found. An increased sensitivity of the cough reflex can be observed in patients with dry cough. Symptomatic relief must be considered when the cough interferes with the patient's daily activities and this is effectively treated with antitussive preparations which are available as combinations of codeine or dextromethorphan with antihistamines, decongestants and expectorants Antitussives are used for effective symptomatic relief of dry or non-productive cough. First generation antihistamines like chlorpheniramine and centrally acting opioid derivatives like codeine are often used alone or in combination in the management of nonspecific cough. Sedation caused by these is valuable, particularly if the cough is disturbing the sleep. Although there is extensive experimental data on single agent antitussives and antitussive combinations, there is a major paucity of published literature on these combinations in nonspecific cough. Treatment of dry cough remains a challenge in some patients and this article reviews the scope of the current drugs and combination of Codeine and Chlorpheniramine in the effective management of dry cough.

  6. Treatment of Drug Abuse: An Overview. National Clearinghouse for Drug Abuse Information Report Series 34, Number 1.

    ERIC Educational Resources Information Center

    National Inst. on Drug Abuse (DHEW/PHS), Rockville, MD. National Clearinghouse for Drug Abuse Information.

    This report presents a brief review of the development of methods and programs for treatment of drug abusers in the United States. In order to limit the scope of the report, discussion of the treatment of alcohol abuse and alcoholism is excluded. The report focuses primarily on the treatment of opiate dependence, since most of the experience on…

  7. Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma

    PubMed Central

    Kato, Hiroyuki; Yoshida, Hideo; Taniguch, Hiroyoshi; Nomura, Ryutaro; Sato, Kengo; Suzuki, Ichiro; Nakata, Ryo

    2015-01-01

    AIM: To investigate the safety and efficacy of the Cyberknife treatment for patients with advanced or terminal stage hepatocellular carcinoma (HCC). METHODS: Patients with HCC with extrahepatic metastasis or vascular or bile duct invasion were enrolled between May 2011 and June 2015. The Cyberknife was used to treat each lesion. Treatment response scores were based on Response Evaluation Criteria in Solid Tumors v1.1. The trends of tumor markers, including alpha fetoprotein (AFP) and proteins induced by vitamin K absence II (PIVKA II) were assessed. Prognostic factors for tumor response and tumor markers were evaluated with Fisher’s exact test and a logistic regression model. Survival was evaluated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Sixty-five patients with 95 lesions were enrolled. Based on the Barcelona Clinic Liver Cancer classification, all patients were either in the advanced or terminal stage of the disease. The target lesions were as follows: 52 were bone metastasis; 9, lung metastasis; 7, brain metastasis; 9, portal vein invasion; 4, hepatic vein invasion; 4, bile duct invasion; and 10 other lesion types. The response rate and disease control rate were 34% and 53%, respectively. None of the clinical factors correlated significantly with tumor response. Fiducial marker implantation was associated with better control of both AFP (HR = 0.152; 95%CI: 0.026-0.887; P = 0.036) and PIVKA II (HR = 0.035; 95%CI: 0.003-0.342; P = 0.004). The median survival time was 9 mo (95%CI: 5-15 mo). Terminal stage disease (HR = 9.809; 95%CI: 2.589-37.17, P < 0.001) and an AFP of more than 400 ng/mL (HR = 2.548; 95%CI: 1.070-6.068, P = 0.035) were associated with worse survival. A radiation dose higher than 30 Gy (HR = 0.274; 95%CI: 0.093-0.7541, P = 0.012) was associated with better survival. In the 52 cases of bone metastasis, 36 patients (69%) achieved pain relief. One patient had cerebral

  8. [Research advances in gene polymorphisms in biological pathways of drugs for asthma].

    PubMed

    Guo, Dan-Dan; Zheng, Xiang-Rong

    2016-06-01

    The studies on gene polymorphisms in biological pathways of the drugs for the treatment of asthma refer to the studies in which pharmacogenetic methods, such as genome-wide association studies, candidate gene studies, genome sequencing, admixture mapping analysis, and linkage disequilibrium, are used to identify, determine, and repeatedly validate the effect of one or more single nucleotide polymorphisms on the efficacy of drugs. This can provide therapeutic strategies with optimal benefits, least side effects, and lowest costs to patients with asthma, and thus realize individualized medicine. The common drugs for asthma are β2 receptor agonists, glucocorticoids, and leukotriene modifiers. This article reviews the research achievements in polymorphisms in biological pathways of the common drugs for asthma, hoping to provide guidance for pharmacogenetic studies on asthma in future and realize individualized medicine for patients with asthma soon.

  9. Treatment approaches in patients with advanced non-small cell lung cancer and poor performance status.

    PubMed

    Govindan, Ramaswamy; Garfield, David H

    2004-12-01

    It is estimated that 30% to 40% of patients with advanced non-small cell lung cancer (NSCLC) have a poor performance status (PS)-defined as a score of 2 or higher on the Eastern Cooperative Oncology Group scale-because of their disease burden, comorbidities, or both. Survival is shorter in these patients than in those with a better PS, and they do not tolerate chemotherapy as well. There is now evidence that PS2 patients with advanced NSCLC can benefit from single-agent chemotherapy with drugs such as vinorelbine, gemcitabine, paclitaxel, pemetrexed, and docetaxel and that combination chemotherapy may have additional advantages. The optimal treatment for PS2 patients with NSCLC, however, has yet to be determined. The case histories in this article demonstrate that PS2 patients are a heterogeneous group and that selecting the chemotherapy for each patient must take into consideration comorbidities and disease-related symptoms, as well as the potential toxicity of treatment. Large prospective clinical trials are needed to determine whether, and in which patients, combination chemotherapy or novel agents, such as the epidermal growth factor receptor inhibitors or paclitaxel poliglumex, have advantages. Three large phase III trials-Selective Targeting for Efficacy in Lung Cancer, Lower Adverse Reactions trials (STELLAR)-are now being conducted in PS2 patients with NSCLC. It is hoped that their findings will aid in determining the best treatment options for these patients.

  10. An Advanced Leakage Scheme for Neutrino Treatment in Astrophysical Simulations

    NASA Astrophysics Data System (ADS)

    Perego, A.; Cabezón, R. M.; Käppeli, R.

    2016-04-01

    We present an Advanced Spectral Leakage (ASL) scheme to model neutrinos in the context of core-collapse supernovae (CCSNe) and compact binary mergers. Based on previous gray leakage schemes, the ASL scheme computes the neutrino cooling rates by interpolating local production and diffusion rates (relevant in optically thin and thick regimes, respectively) separately for discretized values of the neutrino energy. Neutrino trapped components are also modeled, based on equilibrium and timescale arguments. The better accuracy achieved by the spectral treatment allows a more reliable computation of neutrino heating rates in optically thin conditions. The scheme has been calibrated and tested against Boltzmann transport in the context of Newtonian spherically symmetric models of CCSNe. ASL shows a very good qualitative and a partial quantitative agreement for key quantities from collapse to a few hundreds of milliseconds after core bounce. We have proved the adaptability and flexibility of our ASL scheme, coupling it to an axisymmetric Eulerian and to a three-dimensional smoothed particle hydrodynamics code to simulate core collapse. Therefore, the neutrino treatment presented here is ideal for large parameter-space explorations, parametric studies, high-resolution tests, code developments, and long-term modeling of asymmetric configurations, where more detailed neutrino treatments are not available or are currently computationally too expensive.

  11. Advances in Medications and Tailoring Treatment for Alcohol Use Disorder

    PubMed Central

    Seneviratne, Chamindi; Johnson, Bankole A.

    2015-01-01

    Alcohol use disorder (AUD) is a chronic heritable brain disorder with a variable clinical presentation. This variability, or heterogeneity, in clinical presentation suggests complex interactions between environmental and biological factors, resulting in several underlying pathophysiological mechanisms in the development and progression of AUD. Classifying AUD into subgroups of common clinical or pathological characteristics would ease the complexity of teasing apart underlying molecular mechanisms. Genetic association analyses have revealed several polymorphisms—small differences in DNA—that increase a person’s vulnerability to develop AUD and other alcohol-related intermediate characteristics, such as severity of drinking, age of AUD onset, or measures of craving. They also have identified polymorphisms associated with reduced drinking. Researchers have begun utilizing these genetic polymorphisms to identify alcoholics who might respond best to various treatments, thereby enhancing the effectiveness of currently tested medications for treating AUD. This review compares the efficacy of medications tested for treatment of AUD with and without incorporating genetics. It then discusses advances in pre-clinical genetic and genomic studies that potentially could be adapted to clinical trials to improve treatment efficacy. Although a pharmacogenetic approach is promising, it is relatively new and will need to overcome many challenges, including inadequate scientific knowledge and social and logistic constraints, to be utilized in clinical practice. PMID:26259086

  12. Advances in the Understanding and Treatment of Male Urethritis.

    PubMed

    Bachmann, Laura H; Manhart, Lisa E; Martin, David H; Seña, Arlene C; Dimitrakoff, Jordan; Jensen, Jørgen Skov; Gaydos, Charlotte A

    2015-12-15

    Neisseria gonorrhoeae and Chlamydia trachomatis are well-documented urethral pathogens, and the literature supporting Mycoplasma genitalium as an etiology of urethritis is growing. Trichomonas vaginalis and viral pathogens (herpes simplex virus types 1 and 2 and adenovirus) can cause urethritis, particularly in specific subpopulations. New data are emerging regarding the potential role of bacterial vaginosis-associated bacteria in urethritis, although results are inconsistent regarding the pathogenic role of Ureaplasma urealyticum in men. Mycoplasma hominis and Ureaplasma parvum do not appear to be pathogens. Men with suspected urethritis should undergo evaluation to confirm urethral inflammation and etiologic cause. Although nucleic acid amplification testing would detect N. gonorrhoeae and C. trachomatis (or T. vaginalis if utilized), there is no US Food and Drug Administration-approved clinical test for M. genitalium available in the United States at this time. The varied etiologies of urethritis and lack of diagnostic options for some organisms present treatment challenges in the clinical setting.

  13. Novel targeted agents for the treatment of advanced breast cancer.

    PubMed

    de la Vega, Máximo; Díaz-Cantón, Enrique; Alvarez, Ricardo H

    2012-05-01

    The discovery of the molecular processes involved in cancer development has led to the design of an array of targeted agents. These agents, directed to specific proteins in the machinery of cancer cells, interfere with vital cascades involved in cell invasion, metastasis, apoptosis, cell-cycle control and angiogenesis. In breast cancer, the main pathways studied and targeted by drugs are the HER2 pathway, EGFR, VEGF, PI3K/Akt/mammalian target of rapamycin (PI3K-M-Tor), IGF/IGFR, poly(ADP ribose) polymerase 1, HDAC and many others. In this review, we present the most promising studies of these new targeted therapies and novel combination of targeted therapies with cytotoxic agents for the treatment of breast cancer patients. PMID:22571614

  14. Advances in the Understanding and Treatment of Male Urethritis.

    PubMed

    Bachmann, Laura H; Manhart, Lisa E; Martin, David H; Seña, Arlene C; Dimitrakoff, Jordan; Jensen, Jørgen Skov; Gaydos, Charlotte A

    2015-12-15

    Neisseria gonorrhoeae and Chlamydia trachomatis are well-documented urethral pathogens, and the literature supporting Mycoplasma genitalium as an etiology of urethritis is growing. Trichomonas vaginalis and viral pathogens (herpes simplex virus types 1 and 2 and adenovirus) can cause urethritis, particularly in specific subpopulations. New data are emerging regarding the potential role of bacterial vaginosis-associated bacteria in urethritis, although results are inconsistent regarding the pathogenic role of Ureaplasma urealyticum in men. Mycoplasma hominis and Ureaplasma parvum do not appear to be pathogens. Men with suspected urethritis should undergo evaluation to confirm urethral inflammation and etiologic cause. Although nucleic acid amplification testing would detect N. gonorrhoeae and C. trachomatis (or T. vaginalis if utilized), there is no US Food and Drug Administration-approved clinical test for M. genitalium available in the United States at this time. The varied etiologies of urethritis and lack of diagnostic options for some organisms present treatment challenges in the clinical setting. PMID:26602615

  15. Emerging Drugs for the Treatment of Diabetic Ulcers

    PubMed Central

    Tecilazich, Francesco; Dinh, Thanh L.; Veves, Aristidis

    2013-01-01

    Introduction Diabetic ulcers are chronic non-healing ulcerations that despite the available medical tools still result in high amputation rates. Growing evidence suggests that alteration of the biochemical milieu of the chronic wound plays a significant role in diabetic wound healing impairment. Areas covered The basic pathophysiology and the conventional treatment strategy of diabetic foot ulcers have been reviewed in the first section. In the second part we describe the most up-to-date bench and translational research in the field. The third section focuses on the drugs currently under development and the ongoing clinical trials evaluating their safety and efficacy. Finally, we analyze the major drug development issues and the possible scientific approaches to overcome them. Expert opinion Significant strides in understanding the chronic wound development have led to the development of topical therapies to address aberrant expression of growth factors and overexpression of inflammatory cytokines. Current research in our lab suggests that in while decreased growth factor expression occurs at the local wound level, increased systemic serum levels of growth factors suggest growth factor resistance. PMID:23687931

  16. Myopathy during treatment with the antianginal drug ranolazine.

    PubMed

    Kassardjian, Charles D; Tian, Xia; Vladutiu, Georgirene; Wong, Lee-Jun; Milone, Margherita

    2014-12-15

    Ranolazine is a medication indicated for treatment of chronic angina and is a partial inhibitor of the fatty acid β-oxidation. We present an adult patient who developed subacute progressive muscle weakness and exercise-induced myalgia, soon after increasing the daily dose of ranolazine, in the setting of therapy with simvastatin. CK persisted normal throughout the duration of the weakness and muscle biopsy showed a lipid storage myopathy for which no underlying genetic defect was identified. Discontinuation of both drugs resulted in clinical improvement. Although simvastatin may have contributed to the myopathy, the temporal relation between the increase in ranolazine dose and the onset of the weakness would favor ranolazine as major culprit for the weakness.

  17. Barriers to drug treatment for IDU couples: the need for couple-based approaches.

    PubMed

    Simmons, Janie; McMahon, James M

    2012-01-01

    This qualitative study examines the interpersonal and structural barriers to drug treatment program entry, retention, and outcomes experienced by injection drug-using couples, and the program policies regarding injection drug-using couples seeking treatment in New York, New York. Our findings reveal a mismatch between the substantial need for concurrent and coordinated treatment for partnered injection-drug users and programmatic policies that are antithetical to such treatment approaches. This discrepancy can be attributed to the lack of viable options for couple-focused treatment approaches that fit within the current drug treatment system. We provide a rationale and a roadmap for the development of innovative approaches for couple-based drug treatment.

  18. Neuropsychological resiliency after treatment for advanced stage neuroblastoma.

    PubMed

    Carpentieri, S C; Diller, L R

    2005-06-01

    The purpose of this study was to describe the neuropsychological functioning of survivors of advanced stage neuroblastoma. In all, 16 survivors, diagnosed at a median of 2.8 years, who had received intensive chemotherapy and surgical treatments, were identified; 11 had received myeloablative consolidation therapy, eight with total body irradiation (TBI). All patients were evaluated with a neuropsychological assessment battery at a median age of 8.8 years. Analyses included comparison of the performances of the TBI group vs the no-TBI group; determination of whether the proportion of individuals with impaired or superior performance on each measure exceeded normative expectations; and performance indexes reflecting patterns of performance. Results indicate no significant deleterious impact of TBI and/or presence or absence of myeloablative therapy on neurocognitive and neurobehavioral functioning. For this cohort, resilience to neuropsychological vulnerability was observed, which included the emergence of a profile of full-scale IQ, verbal IQ, and mathematical achievement well above average expectations. We concluded that the results document a lack of neuropsychological morbidity among this cohort of survivors of advanced stage neuroblastoma, regardless of the inclusion of TBI. Moreover, a striking pattern of excellent neurocognitive functioning with intact neurobehavioral functioning was observed.

  19. Development of Advanced Multi-Modality Radiation Treatment Planning Software

    SciTech Connect

    Nigg, D W; Hartmann Siantar, C

    2002-02-19

    The Idaho National Engineering and Environmental Laboratory (INEEL) has long been active in development of advanced Monte-Carlo based computational dosimetry and treatment planning methods and software for advanced radiotherapy, with a particular focus on Neutron Capture Therapy (NCT) and, to a somewhat lesser extent, Fast-Neutron Therapy. The most recent INEEL software product system of this type is known as SERA, Simulation Environment for Radiotherapy Applications. SERA is at a mature level in its life cycle, it has been licensed for research use worldwide, and it has become well established as a computational tool for research. However, along with its strengths, SERA also has some limitations in its structure and computational methodologies. More specifically, it is optimized only for neutron-based applications. Although photon transport can be computed with SERA, the simplified model that is used is designed primarily for photons produced in the neutron transport process. Thus SERA is not appropriate for applications to, for example, standard external-beam photon radiotherapy, which is by far more commonly used in the clinic than neutron based therapy.

  20. Advances in endoscopic retrograde cholangiopancreatography for the treatment of cholangiocarcinoma

    PubMed Central

    Uppal, Dushant S; Wang, Andrew Y

    2015-01-01

    Cholangiocarcinoma (CCA) is a malignancy of the bile ducts that carries high morbidity and mortality. Patients with CCA typically present with obstructive jaundice, and associated complications of CCA include cholangitis and biliary sepsis. Endoscopic retrograde cholangiopancreatography (ERCP) is a valuable treatment modality for patients with CCA, as it enables internal drainage of blocked bile ducts and hepatic segments by using plastic or metal stents. While there remains debate as to if bilateral (or multi-segmental) hepatic drainage is required and/or superior to unilateral drainage, the underlying tenant of draining any persistently opacified bile ducts is paramount to good ERCP practice and good clinical outcomes. Endoscopic therapy for malignant biliary strictures from CCA has advanced to include ablative therapies via ERCP-directed photodynamic therapy (PDT) or radiofrequency ablation (RFA). While ERCP techniques cannot cure CCA, advancements in the field of ERCP have enabled us to improve upon the quality of life of patients with inoperable and incurable disease. ERCP-directed PDT has been used in lieu of brachytherapy to provide neoadjuvant local tumor control in patients with CCA who are awaiting liver transplantation. Lastly, mounting evidence suggests that palliative ERCP-directed PDT, and probably ERCP-directed RFA as well, offer a survival advantage to patients with this difficult-to-treat malignancy. PMID:26140095