Full Text Available Steven Okoli, Claire HarrisonDepartment of Haematology, Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London, UKAbstract: In 1934, Epstein and Goedel used the term hemorrhagic thrombocythemia to describe a disorder characterized by permanent elevation of a platelet count to more than three times normal, hyperplasia of megakaryocytes, and the tendency for venous thrombosis and spontaneous hemorrhage. Over the last 75 years, and particularly in the past 6 years, major progress has been made in our understanding of essential thrombocythemia (ET and its pathogenesis with the identification of the highly prevalent JAK-2 V617F and other mutations. Current management of this condition is based upon historical data and with treatments that have not changed significantly for nearly two decades. This study discusses this and recent progress, highlighting exciting new data with old and new drugs, as well as which patients in particular should be evaluated for these new therapies.Keywords: essential thrombocythemia, interferon, JAK inhibitor
Nelson, Michael E; Bryant, Sean M; Aks, Steven E
Many new emerging drugs of abuse are marketed as legal highs despite being labeled "not for human consumption" to avoid regulation. The availability of these substances over the Internet and in "head shops" has lead to a multitude of emergency department visits with severe complications including deaths worldwide. Despite recent media attention, many of the newer drugs of abuse are still largely unknown by health care providers. Slight alterations of the basic chemical structure of substances create an entirely new drug no longer regulated by current laws and an ever-changing landscape of clinical effects. The purity of each substance with exact pharmacokinetic and toxicity profiles is largely unknown. Many of these substances can be grouped by the class of drug and includes synthetic cannabinoids, synthetic cathinones, phenethylamines, as well as piperazine derivatives. Resultant effects generally include psychoactive and sympathomimetic-like symptoms. Additionally, prescription medications, performance enhancing medications, and herbal supplements are also becoming more commonly abused. Most new drugs of abuse have no specific antidote and management largely involves symptom based goal directed supportive care with benzodiazepines as a useful adjunct. This paper will focus on the history, epidemiology, clinical effects, laboratory analysis, and management strategy for many of these emerging drugs of abuse. Copyright © 2014 Elsevier Inc. All rights reserved.
The WHO recommendation on essential drugs for cancer chemotherapy has been updated. General principles on the proper role of cancer chemotherapeutic agents in relation to efficacy and on the classification of tumours with respect to their curative potential are discussed. Curable cancers and those cancers where the cost-benefit ratio clearly favours drug treatment can be managed appropriately based on only 24 drugs. Fourteen of them should ideally be available for the treatment of the ten mos...
Larson, Theresa; Nussenblatt, Robert B.; Sen, H. Nida
Importance of the Field Uveitis is a challenging disease covering both infectious and noninfectious conditions. The current treatment strategies are hampered by the paucity of randomized controlled trials (RCTs) and few trials comparing efficacy of different agents. Areas Covered in this Review This review describes the current and future treatments of uveitis. A literature search was performed in PUBMED from 1965 to 2010 on drugs treating ocular inflammation with emphasis placed on more recent, larger studies. What the Reader Will Gain Readers should gain a basic understanding of current treatment strategies beginning with corticosteroids and transitioning to steroid sparing agents. Steroid sparing agents include the antimetabolites which include methotrexate, azathioprine, and mycophenolate mofetil; the calcineurin inhibitors which include cyclosporine, tacrolimus; alkylating agents which include cyclophosphamide and chlorambucil; and biologics which include the TNF-α inhibitors infliximab, adalimumab, and etanercept; daclizumab, interferon α2a, and rituximab. Take Home Message Newer agents are typically formulated from existing drugs or developed based on new advances in immunology. Future treatment will require a better understanding of the mechanisms involved in autoimmune diseases and better delivery systems in order to provide targeted treatment with minimal side effects. PMID:21210752
Tibbitt, Mark W; Dahlman, James E; Langer, Robert
Medicine relies on the use of pharmacologically active agents (drugs) to manage and treat disease. However, drugs are not inherently effective; the benefit of a drug is directly related to the manner by which it is administered or delivered. Drug delivery can affect drug pharmacokinetics, absorption, distribution, metabolism, duration of therapeutic effect, excretion, and toxicity. As new therapeutics (e.g., biologics) are being developed, there is an accompanying need for improved chemistries and materials to deliver them to the target site in the body, at a therapeutic concentration, and for the required period of time. In this Perspective, we provide an historical overview of drug delivery and controlled release followed by highlights of four emerging areas in the field of drug delivery: systemic RNA delivery, drug delivery for localized therapy, oral drug delivery systems, and biologic drug delivery systems. In each case, we present the barriers to effective drug delivery as well as chemical and materials advances that are enabling the field to overcome these hurdles for clinical impact.
Cozzolino, Mario; Tomlinson, James; Walsh, Liron; Bellasi, Antonio
Secondary hyperparathyroidism (SHPT), a common, serious, and progressive complication of chronic kidney disease (CKD), is characterized by elevated serum parathyroid hormone (PTH), parathyroid gland hyperplasia, and mineral metabolism abnormalities. These disturbances may result in CKD-mineral and bone disorder (CKD-MBD), which is associated with poor quality of life and short life expectancy. The goal of SHPT treatment is to maintain PTH, calcium, and phosphorus within accepted targeted ranges. This review highlights the pathogenesis of SHPT and current SHPT therapeutic approaches, including the use of low-phosphate diets, phosphate binders, 1,25-dihydroxyvitamin D3 (calcitriol) and its analogs, calcimimetics, and parathyroidectomy in addition to discussing emerging drugs in development for SHPT. Numerous studies indicate that mineral abnormalities occur early in the course of CKD, are prevalent by the time patients enter dialysis, and foreshadow a risk of cardiovascular and all-cause mortality. Several newly developed compounds may potentially overcome the limitations of current SHPT therapies. If emerging therapies can reduce PTH, normalize mineral metabolism, promote treatment adherence, and reduce the risk of side effects, they may provide the requisite features for improving long-term outcomes in patients with SHPT receiving dialysis and reduce the risks of CKD-MBD.
To assess the availability of essential drugs and the perceptions of clients on drugs situation in the primary health centres of Tafa Local Government Area, north central Nigeria. Checklist consisting ofminimum drugs expected in a generic primary health centre developed by the National Primary Health Care Development ...
As the patents on widely used biological drugs to treat cancer expire, biosimilar drugs are being developed for the treatment of patients with cancer. You can learn how biosimilars may expand treatment options in this Cancer Currents blog post.
Davis, Gregory G
Drug abusers have access to new, more potent compounds that evade existing laws by virtue of their novel chemical structures. These drugs are available for purchase at stores and over the internet. The drugs are not illegal because they are so new that laws have not yet been passed to ban them. These drugs are leading to emergency department visits for cardiovascular, neurologic, and psychiatric complications. Standard drug screens are not designed to detect these new substances. The internet provides access to drugs for substance abusers but also provides physicians speed of access to the habits of substance abusers.
Essential drugs for cancer chemotherapy were reviewed in a consultation convened by WHO in Geneva. General principles regarding the proper role of cancer chemotherapeutic agents in relation to other established treatment modalities and the classification of tumours with respect to curative potential are discussed. Curable cancers and those cancers where the cost-benefit ratio clearly favours drug treatment can be managed appropriately using only 14 drugs.
Extensively drug-resistant tuberculosis (XDR TB) outbreaks have been reported in South Africa, and strains have been identified on 6 continents. Dr. Peter Cegielski, team leader for drug-resistant TB with the Division of Tuberculosis Elimination at CDC, comments on a multinational team's report on this emerging global public health threat. Created: 3/1/2007 by Emerging Infectious Diseases. Date Released: 3/26/2007.
Extensively drug-resistant tuberculosis (XDR TB) outbreaks have been reported in South Africa, and strains have been identified on 6 continents. Dr. Peter Cegielski, team leader for drug-resistant TB with the Division of Tuberculosis Elimination at CDC, comments on a multinational team's report on this emerging global public health threat.
Milojevic, Kolia; Chassagnol, Isabelle; Brion, Nathalie; Cléro, Joël; Degrèze, Nathalie; Lambert, Yves
A regional survey was performed between June and September 2002, to evaluate knowledge and attitudes of emergency physicians regarding adverse drug reaction (ADR) reporting in a French district. 100 questionnaires completed by physicians working in emergency departments and/or mobile intensive care units were analysed. The frequency of ADRs encountered by emergency practitioners was estimated at > or = 0.73 per year and per physician. The ADR notification rate in emergency medicine was estimated at advertising ADR reporting procedures could help to improve the notification rate in emergency medicine.
Kessler, R; Ryser, D H
Acute drug intoxication is a medical emergency considering its potential interference with vital functions. All 157 cases with drug overdose admitted to the emergency department of the "Inselspital" in Berne over 183 days between July 1989 and June 1990 were analyzed retrospectively. In the vast majority of cases heroin overdose was involved. In mixed poisonings with heroin mostly flunitrazepam and alcohol contributed to the clinical picture, less commonly cocaine. There were very few intoxications with cocaine alone. A practical approach to the management of patients with certain or suspected drug intoxication presenting with coma and depressed respiration is proposed. In the therapy of acute intoxications with opiates and benzodiazepines there are specific antagonists available. In contrast, therapy of cocaine overdose remains symptomatic. The medical complications of acute heroin and cocaine intoxications are discussed separately.
Musselman, Megan E; Hampton, Jeremy P
Synthetic, or "designer" drugs, are created by manipulating the chemical structures of other psychoactive drugs so that the resulting product is structurally similar but not identical to illegal psychoactive drugs. Originally developed in the 1960s as a way to evade existing drug laws, the use of designer drugs has increased dramatically over the past few years. These drugs are deceptively packaged as "research chemicals," "incense," "bath salts," or "plant food," among other names, with labels that may contain warnings such as "not for human consumption" or "not for sale to minors." The clinical effects of most new designer drugs can be described as either hallucinogenic, stimulant, or opioid-like. They may also have a combination of these effects due to designer side-chain substitutions. The easy accessibility and rapid emergence of new designer drugs have created challenges for health care providers when treating patients presenting with acute toxicity from these substances, many of which can produce significant and/or life-threatening adverse effects. Moreover, the health care provider has no way to verify the contents and/or potency of the agent ingested because it can vary between packages and distributors. Therefore, a thorough knowledge of the available designer drugs, common signs and symptoms of toxicity associated with these agents, and potential effective treatment modalities are essential to appropriately manage these patients. © 2014 Pharmacotherapy Publications, Inc.
Full Text Available Meghna Adhvaryu1, Bhasker Vakharia21Department of Biotechnology, SRK Institute of Computer Education and Applied Sciences, 2R&D, Bhuma Research in Ayurvedic and Herbal Medicine, Surat, Gujarat, IndiaAbstract: Multidrug-resistant tuberculosis has emerged worldwide, with an increasing incidence due to failure of implementation of apparently effective first-line antituberculous therapy as well as primary infection with drug-resistant strains. Failure of current therapy is attributed to a long duration of treatment leading to nonadherence and irregular therapy, lack of patient education about the disease, poverty, irregular supply by care providers, drug–drug interactions in patients coinfected with human immunodeficiency virus (HIV, inadequate regulations causing market overlap and irresponsible drug usage in the private sector, and lack of research, with no addition of new drugs in the last four decades. Present standards of care for the treatment of drug-susceptible tuberculosis, multidrug-resistant tuberculosis, tuberculosis-HIV coinfection, and latent tuberculosis infection are all unsatisfactory. Since 2000, the World Health Organization (WHO has focused on drug development for tuberculosis, as well as research in all relevant aspects to discover new regimens by 2015 and to eliminate tuberculosis as a public health concern by 2050. As a result, some 20 promising compounds from 14 groups of drugs have been discovered. Twelve candidates from eight classes are currently being evaluated in clinical trials. Ongoing research should prioritize identification of novel targets and newer application of existing drugs, discovery of multitargeted drugs from natural compounds, strengthening host factors by immunopotentiation with herbal immunomodulators, as well as protective vaccines before and after exposure, consideration of surgical measures when indicated, development of tools for rapid diagnosis, early identification of resistant strains, and
Patrick M Lank
Full Text Available Introduction: The use of synthetic drugs of abuse in the United States has grown in the last few years, with little information available on how much physicians know about these drugs and how they are treating patients using them. The objective of this study was to assess emergency physician (EP knowledge of synthetic cannabinoids (SC.Methods: A self-administered internet-based survey of resident and attending EPs at a large urban emergency department (ED was administered to assess familiarity with the terms Spice or K2 and basic knowledge of SC, and to describe some practice patterns when managing SC intoxication in the ED.Results: Of the 83 physicians invited to participate, 73 (88% completed surveys. The terms “Spice” and “K2” for SC were known to 25/73 (34% and 36/73 (49% of respondents. Knowledge of SC came most commonly (72% from non-medical sources, with lay publications and the internet providing most respondents with information. Among those with previous knowledge of synthetic cannabinoids, 25% were not aware that SC are synthetic drugs, and 17% did not know they are chemically most similar to marijuana. Among all participants, 80% felt unprepared caring for a patient in the ED who had used synthetic cannabinoids.Conclusion: Clinically active EPs are unfamiliar with synthetic cannabinoids. Even those who stated they had heard of synthetic cannabinoids answered poorly on basic knowledge questions. More education is needed among EPs of all ages and levels of training on synthetic cannabinoids. [West J Emerg Med. 2013;14(5:467–470.
Wurcel, Alysse G.; Merchant, Elisabeth A.; Clark, Roger P.; Stone, David R.
This comprehensive review of infectious and noninfectious syndromes associated with illicit drug use focuses on underrecognized complications of common illicit drugs and constellations of syndromes associated with emerging illicit drugs.
Naven, R T; Louise-May, S
Predictive toxicology plays a critical role in reducing the failure rate of new drugs in pharmaceutical research and development. Despite recent gains in our understanding of drug-induced toxicity, however, it is urgent that the utility and limitations of our current predictive tools be determined in order to identify gaps in our understanding of mechanistic and chemical toxicology. Using recently published computational regression analyses of in vitro and in vivo toxicology data, it will be demonstrated that significant gaps remain in early safety screening paradigms. More strategic analyses of these data sets will allow for a better understanding of their domain of applicability and help identify those compounds that cause significant in vivo toxicity but which are currently mis-predicted by in silico and in vitro models. These 'outliers' and falsely predicted compounds are metaphorical lighthouses that shine light on existing toxicological knowledge gaps, and it is essential that these compounds are investigated if attrition is to be reduced significantly in the future. As such, the modern computational toxicologist is more productively engaged in understanding these gaps and driving investigative toxicology towards addressing them. © The Author(s) 2015.
Singh, Priya C; Ballas, Samir K
The search for effective therapeutic interventions for sickle cell disease (SCD) has been an ongoing endeavor for over 50 years. During this period, only hydroxyurea (HU), which received US FDA approval in February 1998, was identified as an effective therapeutic agent in preventing or ameliorating the frequency of vaso-occlusive crises, acute chest syndrome and the need for blood transfusion. Approximately 25% of patients with sickle cell anemia (SCA), however, do not respond to HU and some patients experiencing serious side effects of this chemotherapeutic agent. Nevertheless, the success of HU opened the sluice gates to identify other effective drug therapies. The objective of this review is to describe the emerging drug therapies for SCA. In this review, we describe the pathophysiology of SCD and provide an in-depth analysis of the current and new pharmacologic therapies in the field. Literature searches involved multiple databases including Medline In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Scopus. SCA is a heterogeneous disease that has caused tremendous global morbidity and early mortality. More effective, individualized and inexpensive therapies are needed. New therapies targeting multiple pathways in its complex pathophysiology are under investigation.
Corny, Jennifer; Pelletier, Elaine; Lebel, Denis; Bussières, Jean-François
Only few medicines are licensed for children. The use of emerging drugs (unmarketed drug, off-label drug with poorly documented use, and/or costly drugs) might represent an essential alternative for pediatric patients. The objective of the study was to assess emerging drug uses rate and profile in our women's and children's centre to support the implementation of an appropriate policy. We identified retrospectively emerging drugs used between 2013-01-01 and 2014-02-28, using computerized pharmacist software extraction of drugs used. Conventional oncologic drugs were excluded. Retrospective analysis of medical charts for patients who received an emerging drug and literature review for each drug were performed to determine efficacy and safety endpoints. Median delays between first intention and final decision to use the drug and between final decision and first administration were calculated. Proportion of patients who experienced a positive evolution under treatment or a side effect possibly related to the drug was calculated. A total of 26 emerging drugs were identified (89 patients, 99 uses). Median treatment duration was 66 days [1-1435]. Median delay between first evocation and final decision to use the drug was 2 days [0-333] and 0 day [0-404] between final decision and first administration. 52/99 (53%) of patients experienced a positive evolution under treatment and 26/99 (26%) experienced a side effect possibly related to emerging drug use. This study allowed us to describe emerging drug uses in a women and children tertiary hospital. It led to the implementation of a local emerging drug use policy ensuring optimal and safe use of these drugs. There is a significant number of emerging drugs used in pediatric which shows positive improvement in 56% of patients. © 2017 Journal of Population Therapeutics and Clinical Pharmacology. All rights reserved.
Meyer, Markus R; Peters, Frank T
The steady increase of new drugs of abuse on the illicit drug market is a great challenge for analytical toxicologists. Because most of these new drugs or drug classes are not included in established analytical methods targeting classic drugs of abuse, analytical procedures must be adapted or new procedures must be developed to cover such new compounds. This review summarizes procedures for analysis of these drugs of abuse published from January 2009 to January 2012 covering the following classes of emerging drugs of abuse as follows: β-keto-amphetamines, pyrrolidinophenones, tryptamines, and synthetic cannabinoids.
Wang, Xiujuan; Thijssen, Bram; Yu, Haiyuan
Author Summary The ultimate goal of medical research is to develop effective treatments for disease with minimal side effects. Currently, about 20% of drug candidates failed at clinical trial phases II and III due to safety issues. Therefore, understanding the determining factors of drug side effects is of paramount importance to human health and the pharmaceutical industry. Here, we present the first systematic study to uncover key factors leading to drug side effects within the framework of...
Squizzato, A.; Romualdi, E.; Middeldorp, S.
BACKGROUND: Polycythaemia vera and essential thrombocythaemia are chronic Philadelphia-negative myeloproliferative disorders, which increase the risk of arterial and venous thrombosis as well as bleeding. In addition to the different therapeutic strategies available, aspirin is often used to prevent
Martinussen, Christoffer; Bojsen-Møller, Kirstine Nyvold; Svane, Maria Saur
INTRODUCTION: The increasing prevalence of obesity represents a huge threat to public health and the current pharmacological treatment options are limited. Bariatric surgery is by far the most effective treatment for severe obesity, highlighting the urgent need for new and improved drug therapies....... Areas covered: Based on the physiological regulation of energy homeostasis, pharmacological strategies to treat obesity are evaluated with focus on drugs in phase 2 and 3 clinical development. The potential impact of these drugs on current treatment standards and the barriers for development...... are discussed and set in a historical perspective of previous antiobesity medications. Expert opinion: The radical effects of bariatric surgery have extended our understanding of the mechanisms controlling appetite and boosted the search for new drug targets in obesity treatment. Accordingly, several compounds...
Hercules Sakkas; Panagiota Gousia; Vangelis Economou; Vassilios Sakkas; Stefanos Petsios; Chrissanthy Papadopoulou
Aim/Background: The emergence of drug-resistant pathogens has drawn attention on medicinal plants for potential antimicrobial properties. The objective of the present study was the investigation of the antimicrobial activity of five plant essential oils on multidrug resistant Gram-negative bacteria. Materials and Methods: Basil, chamomile blue, origanum, thyme, and tea tree oil were tested against clinical isolates of Acinetobacter baumannii (n = 6), Escherichia coli (n = 4), Klebsiella pneum...
Drug abuse remains both a global scourge and a significant social and medical problem ... medicine at the Wits Emergency Medicine Department, ATLS Director, occasional media spokesman, .... Respiratory depression caused by morphine.
Olesen, Jes; Ashina, Messoud
Migraine has a 1-year prevalence of 10% and high socioeconomic costs. Despite recent drug developments, there is a huge unmet need for better pharmacotherapy. In this review we discuss promising anti-migraine strategies such as calcitonin gene-related peptide (CGRP) receptor antagonists and 5....... Tonabersat, a cortical spreading depression inhibitor, has shown efficacy in the prophylaxis of migraine with aura. Several new drug targets such as nitric oxide synthase, the 5-HT(1D) receptor, the prostanoid receptors EP(2) and EP(4), and the pituitary adenylate cyclase receptor PAC1 await development....... The greatest need is for new prophylactic drugs, and it seems likely that such compounds will be developed in the coming decade....
Kinn, Michael; Holzbach, Rüdiger; Pajonk, Frank-Gerald Bernhard
For the first time since the year 2000 the number of death due to substance abuse of illegal drugs has increased in Germany in 2007 (+8 % compared to 2006). Emergency situations due to drug abuse are frequent, particular in big cities. They may be, however, difficult to diagnose and/or treat for an emergency physician on scene because of a lack of diagnostic tools, the local and personal surroundings, and the unknown number and nature of drugs. Many drug intoxications must be considered suicidal. On the other hand, drug intoxications may mask (other) life-threatening conditions. Emergency situations due to withdrawal offer the possibility to motivate patients to take advantage of specialist-guided abstinence programs.
General practitioners are frequently facing medical emergencies. In order to react properly and administer therapy on time, a general practitioner needs to prepare and keep with himself the appropriate set of drugs which could be effectively used for treatment of the emergencies. The following drugs should find their place in the doctor's bag: acetaminophen (for mild and moderate pain, and for fever), morphine (for severe pain), naloxone (for heroin poisoning), ceftriaxone (for meningococcal ...
Boeckxstaens, G. E.
Proton pump inhibitors (PPIs) are very effective and safe drugs for the treatment of erosive and non-erosive gastroesophageal reflux disease (GERD). Nevertheless, a significant proportion of GERD patients (30 - 40%) continue to suffer from symptoms during PPI treatment, which has stimulated the
Counterfeit and substandard pharmaceutical drugs are chiefly rampant in developing countries due to inadequate analytical facilities and lack of regulatory oversight. The production of counterfeit or substandard drugs is broadly problematic. Underestimating it therefore leads to morbidity, mortality, drug resistance, introduction of toxic substances into the body and loss of confidence in health care systems. Medical drugs that are often counterfeited range from antimalarial drugs to antiretroviral drugs with antibiotics being counterfeited the most. This research work, therefore, aims at contributing towards the establishment of measures/processes for distinguishing between fake and genuine amoxicillin drugs. This was achieved by the identification and quantification of the Active Pharmaceutical Ingredient (API) and the excipients in the drug formulation. The major analytical techniques employed for this research work were Instrumental Neutron Activation Analysis (INAA), X-ray Powder Diffraction (XRD), High Performance Liquid Chromatography (HPLC) and in vitro Dissolution Test. The amoxicillin samples analyzed were the foreign generic amoxicillin purchased from Ernest Chemists pharmacy at East Legon, Accra, the National Health Insurance Scheme (NHIS) amoxicillin purchased at Fair Mile pharmacy at West Legon, Accra and the Suspected Fake amoxicillin purchased at Okaishi market. For the establishment of fingerprint for identification of substandard amoxicillin, INAA was used to qualitatively determine the short lived radionuclides (excipients) which then facilitated the correct identification of the API and the excipient phases in each of the amoxicillin groups. The phases identified were Amoxicillin Trihydrate as the excipient, Magnesium Stearate (hydrated) and Magnesium Stearate (anhydrous) as the excipients. For Quality control purposes, High Performance Liquid Chromatography approach and also, the in vitro Dissolution test were conducted on each of the groups of
Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention, 2012
This "Issues in Prevention" focuses on emerging issues concerning drug abuse on college campuses. This issue contains the following articles: (1) Drug Abuse Trends; (2) Q&A With Jim Lange; (3) Bath Salts; (4) Refuse to Abuse; (5) Related Federal Resource; and (6) Higher Education Center Resources.
Full Text Available Background: The re-emergent tremor of Parkinson’s disease (PD is generally recognized as a postural tremor. Phenomenology Shown: A PD patient with a re-emergent tremor occurring during a task (spiral drawing, which on the surface produced a tremor that resembled that of essential tremor (ET. Educational Value: Researchers and clinicians should be aware of features of this re-emergent tremor to help distinguish it from that of ET.
Olesen, Jes; Ashina, Messoud
Migraine has a 1-year prevalence of 10% and high socioeconomic costs. Despite recent drug developments, there is a huge unmet need for better pharmacotherapy. In this review we discuss promising anti-migraine strategies such as calcitonin gene-related peptide (CGRP) receptor antagonists and 5......-hydroxytrypamine (5-HT)(1F) receptor agonists, which are in late-stage development. Nitric oxide antagonists are also in development. New forms of administration of sumatriptan might improve efficacy and reduce side effects. Botulinum toxin A has recently been approved for the prophylaxis of chronic migraine....... Tonabersat, a cortical spreading depression inhibitor, has shown efficacy in the prophylaxis of migraine with aura. Several new drug targets such as nitric oxide synthase, the 5-HT(1D) receptor, the prostanoid receptors EP(2) and EP(4), and the pituitary adenylate cyclase receptor PAC1 await development...
Zuzarte, M; Gonçalves, M J; Cruz, M T; Cavaleiro, C; Canhoto, J; Vaz, S; Pinto, E; Salgueiro, L
This work reports the antifungal activity of Lavandula luisieri essential oils against yeast, dermatophyte and Aspergillus strains responsible for human infections and food contamination. The oil's cytotoxicity and its effect on the yeast-mycelium transition in Candida albicans, an important virulence factor, were also evaluated. Analyses by GC and GC/MS showed a peculiar composition of irregular monoterpenes. Significant differences between the samples occurred in the amounts of 1,8-cineole, fenchone and trans-α-necrodyl acetate. The oil with higher amounts of irregular monoterpenes was the most effective. The influence of the oils on the dimorphic transition in C. albicans was also studied through the germ tube inhibition assay. Filamentation was completely inhibited at concentrations sixteen times lower than the minimal inhibitory concentration. The results support the use of L. luiseiri essential oils in the development of new phytopharmaceuticals and food preservatives and emphasise its antifungal properties at concentrations not cytotoxic or with very low detrimental effects on mammalian cells. Copyright © 2012 Elsevier Ltd. All rights reserved.
Narayan, Ram Narendra; Forsthuber, Thomas; Stüve, Olaf
The identification of effective therapies for progressive forms of multiple sclerosis (MS) has remains a priority and challenge for the global MS community. Despite a few proposed mechanisms, a more complete understanding of the mechanisms involved in the pathogenesis of these MS phenotypes, animal models that incorporate these pathogenic characteristics, novel trial designs, drug repurposing strategies, and new models of collaboration between clinical and basic science personnel may be required in identifying effective therapies. Areas covered: Here, we review the current knowledge on putative pathogenic mechanisms in primary progressive MS (PPMS). Also, the rationale and outcomes of key phase II or III trial initiatives in PPMS are summarized. Future perspectives are outlined. Expert opinion: The recent approval of ocrelizumab is a major milestone forward in the therapy of PPMS. One reason for success of this drug is appropriate patient selection. The ultimate goal in PPMS therapy should be the reversal of disability, and the arrest of disease progression. Our current understanding of PPMS suggests that a combination of immune-modulatory, myelin-restorative, and neuro-regenerative therapies particularly early in the disease course would be a reasonable strategy. Finally, selection of appropriate patients, selection of appropriate outcomes and monitoring therapy is again crucial for success of therapeutic strategies.
Kofi Marfo Osei
Conclusion: Beyond pointing out specific material resource deficiencies at the Surgical Medical Emergency (SME centre, our inventory assessment indicated a need to develop better implementation strategies for infection control policies, to collaborate with other departments on coordination of patient care, and to set a research agenda to develop emergency and acute care protocols that are both effective and sustainable in our setting. Equipment and supplies are essential elements of emergency preparedness that must be both available and ‘ready-to-hand’. Consequently, key factors in determining readiness to provide quality emergency care include supply-chain, healthcare financing, functionality of systems, and a coordinated institutional vision. Lessons learnt may be useful for others facing similar challenges to emergency medicine development.
Murrough, James W.; Yaqubi, Sahab; Sayed, Sehrish; Charney, Dennis S.
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
Laitinen, Riikka; Löbmann, Korbinian; Strachan, Clare J.
The number of active pharmaceutical substances having high therapeutic potential but low water solubility is constantly increasing, making it difficult to formulate these compounds as oral dosage forms. The solubility and dissolution rate, and thus potentially the bioavailability, of these poorly...... water-soluble drugs can be increased by the formation of stabilized amorphous forms. Currently, formulation as solid polymer dispersions is the preferred method to enhance drug dissolution and to stabilize the amorphous form of a drug. The purpose of this review is to highlight emerging alternative...... of mesoporous silicon and silica-based carriers are presented as potential means to increase the stability of amorphous pharmaceuticals....
This work concludes that the overall relative drug lag in the emerging markets has decreased over time and that there are seven key regulatory barriers which need to be targeted in order to make further improvements; ′Western Approval′, local clinical development (LCD, Certificate of Pharmaceutical Product (CPP, Good Manufacturing Practice (GMP, pricing approval, document authentication and harmonisation.
Full Text Available General practitioners are frequently facing medical emergencies. In order to react properly and administer therapy on time, a general practitioner needs to prepare and keep with himself the appropriate set of drugs which could be effectively used for treatment of the emergencies. The following drugs should find their place in the doctor's bag: acetaminophen (for mild and moderate pain, and for fever, morphine (for severe pain, naloxone (for heroin poisoning, ceftriaxone (for meningococcal meningitis, albuterol (for bronchial asthma attack, hydrocortisone (for bronchial asthma attack, glucagon (for severe hypoglycemia, dextrose (for mild to moderate hypoglycemia, diazepam (for febrile convulsions or epileptic status, epinephrine (for anaphylaxis and cardiac arrest, atropine (for symptomatic bradicardia, chloropyramine (for acute allergy, aspirin (for acute myocardial infarction, nitroglycerine (for acute coronary syndrome, metoclopramide (for nausea and vomiting, haloperidol (for delirium, methylergometrine (for control of bleeding after delivery or abortion, furosemide (for acute pulmonary edema and flumazenil (for benzodiazepine poisoning. For each of the listed drugs a physician should well know the recommended doses, indications, contraindications and warnings. All of the listed drugs are either registered in Serbia or available through special import, so general practitioners may fill their bags with all necessary drugs and effectively and safely treat medical emergencies.
Olsen, Louise Cathrine Braun; Færgeman, Nils J.
and validate therapeutic targets and to discover drug candidates for rapidly and effectively generating new interventions for human diseases. The recent emergence of genomic technologies and their application on genetically tractable model organisms like Drosophila melanogaster,Caenorhabditis elegans...... critical roles in the genomic age of biological research and drug discovery. In the present review we discuss how simple biological model organisms can be used as screening platforms in combination with emerging genomic technologies to advance the identification of potential drugs and their molecular...
Rodrigues, Debora G
With the need for innovation in drug discovery and development and changes to patent laws that are enabling greater IP protection, many pharmaceutical companies are pursuing international cooperation agreements with foreign companies as part of a global development strategy to enhance product pipelines. Brazil, the largest pharmaceutical market in Latin America, has improved its infrastructure, scientific and technological capabilities and has created a sustainable strategy to promote drug discovery research activities. Positive economic growth, a stable political structure, expanding patient populations an increasing governmental, private and foreign investments are creating a new landscape for drug R&D in the country. As Brazilian-based pharmaceutical companies become further established, new opportunities for partnerships and collaborative alliances are becoming available for the drug discovery process, as well as for co-manufacturing and co-marketing efforts. This feature review provides an overview of the Brazilian pharmaceutical market and discusses current opportunities, emerging trends and challenges for this expanding market.
Laitinen, Riikka; Löbmann, Korbinian; Strachan, Clare J; Grohganz, Holger; Rades, Thomas
The number of active pharmaceutical substances having high therapeutic potential but low water solubility is constantly increasing, making it difficult to formulate these compounds as oral dosage forms. The solubility and dissolution rate, and thus potentially the bioavailability, of these poorly water-soluble drugs can be increased by the formation of stabilized amorphous forms. Currently, formulation as solid polymer dispersions is the preferred method to enhance drug dissolution and to stabilize the amorphous form of a drug. The purpose of this review is to highlight emerging alternative methods to amorphous polymer dispersions for stabilizing the amorphous form of drugs. First, an overview of the properties and stabilization mechanisms of amorphous forms is provided. Subsequently, formulation approaches such as the preparation of co-amorphous small-molecule mixtures and the use of mesoporous silicon and silica-based carriers are presented as potential means to increase the stability of amorphous pharmaceuticals. Copyright © 2012 Elsevier B.V. All rights reserved.
Castaño Pérez, Guillermo A; Calderón Vallejo, Gustavo A; Berbesi Fernández, Dedsy Yajaira
The ongoing emergence of new synthetic substances that are used as drugs is a constant challenge to public health. Emerging drugs is the concept used in this research project to define the emergence of new psychoactive substances at a given time, a specific context and group, the reemergence of others that some epidemiologists considered had lost their prevalence, and the sudden prevalence of drugs that had low levels of consumption. This research project was carried out using an empirical-analytical approach using a mixed methods study. The convenience sample was made up of 510 drug dependents institutionalized in treatment centers in Medellin in the year 2011. The examination was carried out related to the consumption of emerging drugs. An ad hoc tool was applied to all the drug users in order to identify which of the drugs of this study they considered to be emergent. Once the consumers were identified and selected based on the frequency of consumption, and the prevalence in the last year and last month, a semi-structured interview was carried out to find out details on the substances and their consumption characteristics. Based on the new drug consumers in Medellin, 82.2% were male and 17.8% female. As regards education levels, 58.2% were in high school, 26.8% hold higher technical or college degrees, and 1.4% had no schooling. Only 27.8% held a steady job, occasional employment, or were independent business owners, 40.7% were students and 8.9% were housewives. More than three-quarters (76.3%) were single, and 17.8% had a steady partner. The sample represented all social classes. Of all the emerging drugs found in this study, the prevalence of benzodiazepines stands out (flunitrazepam and clonazepam), life prevalence (LP), 97.5%; last year prevalence (LYP), 67.9%, and last month prevalence (LMP), 46.7%. These were followed by the synthetic drugs (LSD, Ecstasies, amphetamines, GHB, Vegetable Ecstasies, Phencyclidine; Methamphetamine, Ketamine, 2CB), with LP, 96
Hall Ross S
Full Text Available Abstract Background New drug targets are urgently needed for parasites of socio-economic importance. Genes that are essential for parasite survival are highly desirable targets, but information on these genes is lacking, as gene knockouts or knockdowns are difficult to perform in many species of parasites. We examined the applicability of large-scale essentiality information from four model eukaryotes, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus and Saccharomyces cerevisiae, to discover essential genes in each of their genomes. Parasite genes that lack orthologues in their host are desirable as selective targets, so we also examined prediction of essential genes within this subset. Results Cross-species analyses showed that the evolutionary conservation of genes and the presence of essential orthologues are each strong predictors of essentiality in eukaryotes. Absence of paralogues was also found to be a general predictor of increased relative essentiality. By combining several orthology and essentiality criteria one can select gene sets with up to a five-fold enrichment in essential genes compared with a random selection. We show how quantitative application of such criteria can be used to predict a ranked list of potential drug targets from Ancylostoma caninum and Haemonchus contortus - two blood-feeding strongylid nematodes, for which there are presently limited sequence data but no functional genomic tools. Conclusions The present study demonstrates the utility of using orthology information from multiple, diverse eukaryotes to predict essential genes. The data also emphasize the challenge of identifying essential genes among those in a parasite that are absent from its host.
Full Text Available The booming e-commerce and a regulation-less environment online have led to the rise of a new generation of websites that market drugs and other products over the Internet. Some of these drugs are often herbal products or of dubious quality, often marketed with a mix of professional design and unverified/fraudulent claims. Several concerns have arisen from different corners and evidence of malpractice has emerged. But there is a lack of sufficient evidence confirming the concerns.
Goldbach, Jeremy T; Mereish, Ethan H; Burgess, Claire
Prescription drug, e-cigarette, smokeless tobacco, and synthetic marijuana use has risen dramatically in the United States over the past decade. This paper investigates the use of risky substances among adolescents, and examines disparities between sexual minority (i.e., mostly heterosexual and lesbian, gay, bisexual; LGB) and heterosexual adolescents in use of novel and emerging substances. Given the public health risk and the imminence of these substances in the media, emerging drug use was examined in a county wide sample of adolescents in a Southern state. A probability sample of middle and high school students (N = 3012; ages 11-18) using random cluster methods was obtained in a mid-sized school district in the Southeastern United States. LGB adolescents reported higher past-30 day and lifetime use of cigarettes (AORs =2.77, 2.90, respectively), smokeless tobacco (lifetime only: AOR = 1.88), e-cigarettes (lifetime only; AOR = 1.92), alcohol (AORs = 1.7, 2.20), marijuana (AORs = 3.02, 3.06), synesthetic marijuana (AORs = 3.77, 2.48), and prescription drugs (AORs = 3.82, 2.55). Adolescents who self-identified as "mostly heterosexual" reported higher lifetime cigarette use, and past 30-day use of e-cigarettes and prescription drugs as compared with heterosexual adolescents. Our results are notable given the dearth of data documenting use of increasingly emerging or "trendy" substances such as prescription drugs. More research is needed to understand the underlying cause of these disparities, and efforts should be targeted toward this population to reduce negative outcomes from misuse.
Mignani, Serge; El Kazzouli, Saïd; Bousmina, Mosto; Majoral, Jean-Pierre
Drugs are introduced into the body by numerous routes such as enteral (oral, sublingual and rectum administration), parenteral (intravascular, intramuscular, subcutaneous and inhalation administration), or topical (skin and mucosal membranes). Each route has specific purposes, advantages and disadvantages. Today, the oral route remains the preferred one for different reasons such as ease and compliance by patients. Several nanoformulated drugs have been already approved by the FDA, such as Abelcet®, Doxil®, Abraxane® or Vivagel®(Starpharma) which is an anionic G4-poly(L-lysine)-type dendrimer showing potent topical vaginal microbicide activity. Numerous biochemical studies, as well as biological and pharmacological applications of both dendrimer based products (dendrimers as therapeutic compounds per se, like Vivagel®) and dendrimers as drug carriers (covalent conjugation or noncovalent encapsulation of drugs) were described. It is widely known that due to their outstanding physical and chemical properties, dendrimers afforded improvement of corresponding carried-drugs as dendrimer-drug complexes or conjugates (versus plain drug) such as biodistribution and pharmacokinetic behaviors. The purpose of this manuscript is to review the recent progresses of dendrimers as nanoscale drug delivery systems for the delivery of drugs using enteral, parenteral and topical routes. In particular, we focus our attention on the emerging and promising routes such as oral, transdermal, ocular and transmucosal routes using dendrimers as delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.
Ridde, Valéry; Nitièma, Abdoulaye P; Dadjoari, Moussa
Despite the formulation of the Bamako initiative in 1992 in Burkina Faso, not until 2001 and the launching of a project by a nongovernmental organization was the policy really implemented in a region of the country. One of the goals of this policy is to improve access to health care by using generic essential drugs. The objective of this article is to summarize the results of the evaluation of the project's ability to improve the population's access to drugs. The project lasted three years (2001-2003) and the interventions took place in 41 basic health centres of three districts. According to WHO, improving access to drugs requires consideration of four essential factors: rational use, affordable prices, financial viability, and effectiveness of the distribution. The average number of drugs prescribed per prescription sheet (n = 1061) was 2.4; 93% of the drugs were prescribed by their generic name (international non-proprietary names); 44% of infant diarrheas were treated with oral rehydration salt. National drug prices were respected but not the directives aiming at exempting from payment or subsidizing certain population sub-groups (children, indigents). The average annual cash flow of the basic health centres was 1.2 million F CFA and it increased by 854% compared to the beginning of the project. The cost-recovery scheme for administrative expenses was 106%. The average annual availability of the 10 essential drugs was 89%. Utilization rates increased (0.13 in 1999 to 0.21 in 2003) but not significantly differently than in other basic health centres of the area not supported by the project (p = 0.084). The project succeeded in improving access to these drugs for the overall population but not for the worst-off. The drugs are now geographically available for all and financially accessible for those who can afford to pay. The intervention strategy supported the sustainability of the project's activities but much remains to be done to provide the poorest with
Full Text Available Fe-S centers exhibit strong electronic plasticity, which is of importance for insuring fine redox tuning of protein biological properties. In accordance, Fe-S clusters are also highly sensitive to oxidation and can be very easily altered in vivo by different drugs, either directly or indirectly due to catabolic by-products, such as nitric oxide species (NOS or reactive oxygen species (ROS. In case of metal ions, Fe-S cluster alteration might be the result of metal liganding to the coordinating sulfur atoms, as suggested for copper. Several drugs presented through this review are either capable of direct interaction with Fe-S clusters or of secondary Fe-S clusters alteration following ROS or NOS production. Reactions leading to Fe-S cluster disruption are also reported. Due to the recent interest and progress in Fe-S biology, it is very likely that an increasing number of drugs already used in clinics will emerge as molecules interfering with Fe-S centers in the near future. Targeting Fe-S centers could also become a promising strategy for drug development.
Chao, Jianqian; Gu, Jiangyi; Zhang, Hua; Chen, Huanghui; Wu, Zhenchun
Essential medicine policy is a successful global health policy to promote rational drug use. The aim of this study was to evaluate the impact of the National Essential Medicines Policy (NEMP) on the rational drug use in primary care institutions in Jiangsu Province of China. In this exploratory study, a multistage, stratified, random sampling was used to select 3400 prescriptions from 17 primary care institutions who implemented the NEMP before (Jan 2010) and after the implementation of the NEMP (Jan 2014). The analyses were performed in SPSS 18.0 and SPSS Clementine client. After the implementation of the NEMP, the percentage of prescribed EML (Essential Medicines List) drugs rose significantly, the average number of drugs per prescription and average cost per prescription were declined significantly, while the differences of the prescription proportion of antibiotics and injection were not statistically significant. BP (Back Propagation) neural network analysis showed that the average number of drugs per prescription, the number of using antibiotics and hormone, regional differences, size of institutions, sponsorship, financial income of institutions, doctor degree, outpatient and emergency visits person times were important factors affecting the prescription costs, among these the average number of drugs per prescription has the greatest effect. The NEMP can promote the rational use of drugs in some degree, but its role is limited. We should not focus only on the EML but also make comprehensive NEMP.
Li, Zhuge; Shu, Defeng; Xia, Mei; Gao, Dehai; Lu, Dan; Huang, Ning; Tian, Xiaoqing; An, Limei; Li, Shixue; Li, Sheng
At present, China has achieved an initial establishment and gradual implementation of a framework for national essential drugs policy. With the further implementation of the national essential drugs policy, it is not clear how the policy works, whether it achieves the original intention of essential drugs policy, and what impact essential drugs policy exerts on the primary health care system. In view of it, we conducted a field research on sample areas of Shandong Province to understand the conditions of the implementation of the essential drugs policy in Shandong Province. From three perspectives of medical institutions, patients and medical staff, this thesis analyzes the impact of essential drugs policy on village-level and township-level health service system, summarizes the effectiveness of implementing essential drugs policy, discovers the problems of various aspects and conducts an in-depth analysis of the causes, and puts forward feasible suggestions to provide reference for improving the essential drugs policy. The assessment results show that the implementation of essential drugs policy in Shandong Province has played a positive role in promoting the sound development of the primary health care system, changed the situation of covering hospital expenses with medicine revenue in the past, contributed to the return of medical institutions to public welfare, and reduced the patient's economic burden of disease. But there emerge many problems as follows: impact on the doctor's diagnosis and treatment due to incompleteness of drug types, and distribution not in place, patient loss and operational difficulty of village clinic. Thus, this thesis makes recommendations of drugs catalog formulation, drug procurement, sales and use, and meanwhile points out that the supporting financial compensation policy and performance appraisal policy and other measures in place are a prerequisite for a positive role of essential drugs policy.
Full Text Available The objective of this work is to elucidate various essential drugs in the Brazil, Russia, India, China and South Africa (BRICS countries. It discusses the opportunities and challenges of the existing biotech infrastructure and the production of drugs and vaccines in member states of the BRICS. This research is based on a systematic literature review between the years 2000 and 2014 of documents retrieved from the databases Embase, PubMed/Medline, Global Health, and Google Scholar, and the websites of relevant international organizations, research institutions and philanthropic organizations. Findings vary from one member state to another. These include useful comparison between the BRICS countries in terms of pharmaceuticals expenditure versus total health expenditure, local manufacturing of drugs/vaccines using technology and know-how transferred from developed countries, and biotech entrepreneurial collaborations under the umbrella of the BRICS region. This study concludes by providing recommendations to support more of inter collaborations among the BRICS countries as well as between BRICS and many developing countries to shrink drug production costs. In addition, this collaboration would also culminate in reaching out to poor countries that are not able to provide their communities and patients with cost-effective essential medicines.
The objective of this work is to elucidate various essential drugs in the Brazil, Russia, India, China and South Africa (BRICS) countries. It discusses the opportunities and challenges of the existing biotech infrastructure and the production of drugs and vaccines in member states of the BRICS. This research is based on a systematic literature review between the years 2000 and 2014 of documents retrieved from the databases Embase, PubMed/Medline, Global Health, and Google Scholar, and the websites of relevant international organizations, research institutions and philanthropic organizations. Findings vary from one member state to another. These include useful comparison between the BRICS countries in terms of pharmaceuticals expenditure versus total health expenditure, local manufacturing of drugs/vaccines using technology and know-how transferred from developed countries, and biotech entrepreneurial collaborations under the umbrella of the BRICS region. This study concludes by providing recommendations to support more of inter collaborations among the BRICS countries as well as between BRICS and many developing countries to shrink drug production costs. In addition, this collaboration would also culminate in reaching out to poor countries that are not able to provide their communities and patients with cost-effective essential medicines.
Full Text Available The mechanisms by which Mycobacterium tuberculosis (Mtb maintains metabolic equilibrium to survive during infection and upon exposure to antimycobacterial drugs are poorly characterized. Ergothioneine (EGT and mycothiol (MSH are the major redox buffers present in Mtb, but the contribution of EGT to Mtb redox homeostasis and virulence remains unknown. We report that Mtb WhiB3, a 4Fe-4S redox sensor protein, regulates EGT production and maintains bioenergetic homeostasis. We show that central carbon metabolism and lipid precursors regulate EGT production and that EGT modulates drug sensitivity. Notably, EGT and MSH are both essential for redox and bioenergetic homeostasis. Transcriptomic analyses of EGT and MSH mutants indicate overlapping but distinct functions of EGT and MSH. Last, we show that EGT is critical for Mtb survival in both macrophages and mice. This study has uncovered a dynamic balance between Mtb redox and bioenergetic homeostasis, which critically influences Mtb drug susceptibility and pathogenicity.
Teräväinen, H; Huttunen, J; Larsen, T A
Eighteen patients with essential tremor were treated for 2 days with a non-selective adrenergic beta-blocking drug (dl-propranolol, 80 mg X 3), a beta-2-selective blocker (ICI-118.551, 50 mg X 3) and placebo (X 3) in a randomized double blind cross-over study. Postural hand tremor was recorded with an accelerometer before administration of the drugs and at the end of each treatment period. Compared with placebo, both the beta-blocking drugs caused a statistically significant decrease in tremor intensity and they possessed approximately similar antitremor potency. Subjective benefit was reported by 12 of the 18 patients receiving ICI-118.551, 13 when on propranolol and 3 when on placebo.
Full Text Available We report results from the first genome-wide application of a rational drug target selection methodology to a metazoan pathogen genome, the completed draft sequence of Brugia malayi, a parasitic nematode responsible for human lymphatic filariasis. More than 1.5 billion people worldwide are at risk of contracting lymphatic filariasis and onchocerciasis, a related filarial disease. Drug treatments for filariasis have not changed significantly in over 20 years, and with the risk of resistance rising, there is an urgent need for the development of new anti-filarial drug therapies. The recent publication of the draft genomic sequence for B. malayi enables a genome-wide search for new drug targets. However, there is no functional genomics data in B. malayi to guide the selection of potential drug targets. To circumvent this problem, we have utilized the free-living model nematode Caenorhabditis elegans as a surrogate for B. malayi. Sequence comparisons between the two genomes allow us to map C. elegans orthologs to B. malayi genes. Using these orthology mappings and by incorporating the extensive genomic and functional genomic data, including genome-wide RNAi screens, that already exist for C. elegans, we identify potentially essential genes in B. malayi. Further incorporation of human host genome sequence data and a custom algorithm for prioritization enables us to collect and rank nearly 600 drug target candidates. Previously identified potential drug targets cluster near the top of our prioritized list, lending credibility to our methodology. Over-represented Gene Ontology terms, predicted InterPro domains, and RNAi phenotypes of C. elegans orthologs associated with the potential target pool are identified. By virtue of the selection procedure, the potential B. malayi drug targets highlight components of key processes in nematode biology such as central metabolism, molting and regulation of gene expression.
Full Text Available Danièle Debruyne,1,2 Reynald Le Boisselier1 1Centre for Evaluation and Information on Pharmacodependence - Addictovigilance (CEIP-A, 2Toxicology and Pharmacology Laboratory, Department of Pharmacology, University Hospital Centre Côte de Nacre, Caen, France Abstract: New psychoactive drugs that have appeared over the last decade are typically dominated by cathinones and synthetic cannabinoids (SCs. SCs have been emerging as recreational drugs because they mimic the euphoria effect of cannabis while still being legal. Sprayed on natural herb mixtures, SCs have been primarily sold as “herbal smoking blends” or “herbal incense” under brand names like “Spice” or “K2”. Currently, SCs pure compounds are available from websites for the combination with herbal materials or for the use in e-cigarettes. For the past 5 years, an ever increasing number of compounds, representative of different chemical classes, have been promoted and now represent a large assortment of new popular drugs of abuse, which are difficult to properly identify. Their legal status varies by country with many government institutions currently pushing for their control. The in vitro binding to CB1/CB2 receptors is usually well-known and considerable differences have been found in the CB1 versus CB2 selectivity and potency within the different SCs, with several structure-activity relations being evident. Desired effects by CB1 agonist users are relaxation/recreative, however, cardiovascular, gastrointestinal, or psychiatric/neurological side effects are commonly reported. At present there is no specific antidote existing if an overdose of designer drugs was to occur, and no curative treatment has been approved by health authorities. Management of acute toxic effects is mainly symptomatic and extrapolated from experience with cannabis. Keywords: synthetic cannabinoids, chemistry, analysis, pharmacology, toxicology, dependence, medical care
Full Text Available Background: Development of resistance to many of the commonly used antibiotics is an impetus for further attempts to search for new antimicrobial agents. Objectives: In the present study, the antibacterial activity of Saturejahortensis essential oil against multi-drug resistant bacteria isolated from the urinary tract infections was investigated. Materials and Methods: During the years 2011 to 2012 a total of 36 strains of pathogenic bacteria including 12 Klebsiellapneumoniae, 12 Escherichia coli and 12 Staphylococcus aureus species were isolated from urine samples of hospitalized patients (Amir Al-Momenin Hospital, Zabol, South-eastern Iran suffering from urinary tract infections. After bacteriological confirmatory tests, the minimum inhibitory concentrations of the essential oil of Saturejahortensis were determined using micro-dilution method. Results: The antibiotic resistance profile of the E. coli isolates were as follows: ceftazidime (50% cefixime (41.6%, tetracycline (75%, erythromycin (58.3%. However K. pneumoniae isolates showed resistance to ceftazidime (33.3%, cefixime (58.3%, erythromycin (75% and S. aureus isolates were resistant to cefixime (33.3%, trimethoprim-sulfamethoxazole (41.66%, penicillin (50%, oxacillin (83.3%, ceftazidime (66.6% and vancomycin (8.3%. The essential oil of this plant had inhibitory effect against most isolates. More than 1/3 of the E. coli isolates showed the lowest MIC (10 ppm whereas more than 1/3 of the K. pneumoniae isolates showed the highest (250 ppm MIC values. In contrast ,equal number of S. aureus isolates showed the low MIC values (10 and 50 ppm, while the heighest MIC (250 ppm was seen in 1/3 of isolates and moderate MIC (100 ppm was seen in one isolate only. Conclusions: The Saturejahortensis essential oil has a potent antimicrobial activity against multi-drug resistant bacteria. The present study confirms the usefullness of this essential oil as antibacterial agent but further research is
Shao, Hui; Li, Shixue; Xu, Lingzhong; Yang, Shuang; Thomas, Nicholas J; Mir, Mohammed Umer; Guo, Zhen; Ning, Bo; Shi, Lizheng
To predict the prospects of the essential drug system by using the Stakeholder Impact Index (SII) and evaluate the current performance of each main stakeholder and suggested dangerous stakeholders and dormant stakeholders. A Delphi method was used, involving 36 experts with experience in implementation and evaluation of the essential drug policy, to construct the circular model as well as evaluate the performance of each stakeholder. The central government was a dominant stakeholder of the whole essential drug system. The provincial governments were definitive stakeholders, whereas local governments and medical institutions were dependent stakeholders. Furthermore, media and drug stores were dormant stakeholders and pharmaceutical manufacturers and delivery enterprises were dangerous stakeholders. Patients, community residents, and medical insurance programs were discretionary stakeholders. The SII for the essential drug system was positive (SII proj ⁎ = 2.72). The overall anticipation of the essential drug policy is optimistic. Letting definitive stakeholders (provincial governments) having more autonomy can efficiently accelerate the pace of implementation of the essential drug policy in the current situation. Central government, however, also needs to construct an experience exchange platform with the aim of building versatile methods for running the essential drug system in all provinces. Pharmaceutical manufacturers and delivery enterprises were dangerous stakeholders for the essential drug policy. Because of their potential threat to the implementation of the policy, the central government should motivate them to support the construction of the essential drug system spontaneously. In that case, provincial governments need to construct a fair, balanced, and self-stabilized bidding platform. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.
Debnath, Anjan; Calvet, Claudia M; Jennings, Gareth; Zhou, Wenxu; Aksenov, Alexander; Luth, Madeline R; Abagyan, Ruben; Nes, W David; McKerrow, James H; Podust, Larissa M
Primary Amoebic Meningoencephalitis (PAM) is caused by Naegleria fowleri, a free-living amoeba that occasionally infects humans. While considered "rare" (but likely underreported) the high mortality rate and lack of established success in treatment makes PAM a particularly devastating infection. In the absence of economic inducements to invest in development of anti-PAM drugs by the pharmaceutical industry, anti-PAM drug discovery largely relies on drug 'repurposing'-a cost effective strategy to apply known drugs for treatment of rare or neglected diseases. Similar to fungi, N. fowleri has an essential requirement for ergosterol, a building block of plasma and cell membranes. Disruption of sterol biosynthesis by small-molecule inhibitors is a validated interventional strategy against fungal pathogens of medical and agricultural importance. The N. fowleri genome encodes the sterol 14-demethylase (CYP51) target sharing ~35% sequence identity to fungal orthologues. The similarity of targets raises the possibility of repurposing anti-mycotic drugs and optimization of their usage for the treatment of PAM. In this work, we (i) systematically assessed the impact of anti-fungal azole drugs, known as conazoles, on sterol biosynthesis and viability of cultured N. fowleri trophozotes, (ii) identified the endogenous CYP51 substrate by mass spectrometry analysis of N. fowleri lipids, and (iii) analyzed the interactions between the recombinant CYP51 target and conazoles by UV-vis spectroscopy and x-ray crystallography. Collectively, the target-based and parasite-based data obtained in these studies validated CYP51 as a potentially 'druggable' target in N. fowleri, and conazole drugs as the candidates for assessment in the animal model of PAM.
Full Text Available Primary Amoebic Meningoencephalitis (PAM is caused by Naegleria fowleri, a free-living amoeba that occasionally infects humans. While considered "rare" (but likely underreported the high mortality rate and lack of established success in treatment makes PAM a particularly devastating infection. In the absence of economic inducements to invest in development of anti-PAM drugs by the pharmaceutical industry, anti-PAM drug discovery largely relies on drug 'repurposing'-a cost effective strategy to apply known drugs for treatment of rare or neglected diseases. Similar to fungi, N. fowleri has an essential requirement for ergosterol, a building block of plasma and cell membranes. Disruption of sterol biosynthesis by small-molecule inhibitors is a validated interventional strategy against fungal pathogens of medical and agricultural importance. The N. fowleri genome encodes the sterol 14-demethylase (CYP51 target sharing ~35% sequence identity to fungal orthologues. The similarity of targets raises the possibility of repurposing anti-mycotic drugs and optimization of their usage for the treatment of PAM. In this work, we (i systematically assessed the impact of anti-fungal azole drugs, known as conazoles, on sterol biosynthesis and viability of cultured N. fowleri trophozotes, (ii identified the endogenous CYP51 substrate by mass spectrometry analysis of N. fowleri lipids, and (iii analyzed the interactions between the recombinant CYP51 target and conazoles by UV-vis spectroscopy and x-ray crystallography. Collectively, the target-based and parasite-based data obtained in these studies validated CYP51 as a potentially 'druggable' target in N. fowleri, and conazole drugs as the candidates for assessment in the animal model of PAM.
Garbayo, E; Ansorena, E; Blanco-Prieto, M J
Current treatments for Parkinson's disease (PD) are aimed at addressing motor symptoms but there is no therapy focused on modifying the course of the disease. Successful treatment strategies have been so far limited and brain drug delivery remains a major challenge that restricts its treatment. This review provides an overview of the most promising emerging agents in the field of PD drug discovery, discussing improvements that have been made in brain drug delivery for PD. It will be shown that new approaches able to extend the length of the treatment, to release the drug in a continuous manner or to cross the blood-brain barrier and target a specific region are still needed. Overall, the results reviewed here show that there is an urgent need to develop both symptomatic and disease-modifying treatments, giving priority to neuroprotective treatments. Promising perspectives are being provided in this field by rasagiline and by neurotrophic factors like glial cell line-derived neurotrophic factor. The identification of disease-relevant genes has also encouraged the search for disease-modifying therapies that function by identifying molecularly targeted drugs. The advent of new molecular and cellular targets like α-synuclein, leucine-rich repeat serine/threonine protein kinase 2 or parkin, among others, will require innovative delivery therapies. In this regard, drug delivery systems (DDS) have shown great potential for improving the efficacy of conventional and new PD therapy and reducing its side effects. The new DDS discussed here, which include microparticles, nanoparticles and hydrogels among others, will probably open up possibilities that extend beyond symptomatic relief. However, further work needs to be done before DDS become a therapeutic option for PD patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
... Treatment There is no definitive cure for essential tremor. Symptomatic drug therapy may include propranolol or other beta blockers and primidone, an anticonvulsant drug. Eliminating tremor "triggers" ...
Morgan, Steven G; Li, Winny; Yau, Brandon; Persaud, Nav
Canada's universal health care system does not include universal coverage of prescription drugs. We sought to estimate the effects of adding universal public coverage of an essential medicines list to existing public drug plans in Canada. We used administrative and market research data to estimate the 2015 shares of the volume and cost of prescriptions filled in the community setting that were for 117 drugs on a model list of essential medicines for Canada. We compared prices of these essential medicines in Canada with prices in the United States, Sweden and New Zealand. We estimated the cost of adding universal public drug coverage of these essential medicines based on anticipated effects on medication use and pricing. The 117 essential medicines on the model list accounted for 44% of all prescriptions and 30% of total prescription drug expenditures in 2015. Average prices of generic essential medicines were 47% lower in the US, 60% lower in Sweden and 84% lower in New Zealand; brand-name drugs were priced 43% lower in the US. Estimated savings from universal public coverage of these essential medicines was $4.27 billion per year (range $2.72 billion to $5.83 billion; 28% reduction) for patients and private drug plan sponsors, at an incremental government cost of $1.23 billion per year (range $373 million to $1.98 billion; 11% reduction). Our analysis showed that adding universal public coverage of essential medicines to the existing public drug plans in Canada could address most of Canadians' pharmaceutical needs and save billions of dollars annually. Doing so may be a pragmatic step forward while more comprehensive pharmacare reforms are planned. © 2017 Canadian Medical Association or its licensors.
Mehdizadeh, Mohammad; Nosrati, Kamran; Hamzeh, Mahtab
Medical emergencies can frequently happen in dental settings and it is critical to outfit the clinic by emergency drugs and equipment. The aim of this study was to evaluate the emergency drugs and equipment in general and specialist dental settings in Babol, Iran. A questionnaire containing closed ended questions about the available emergency drugs and equipment was used in this descriptive-analytical study. Data were subjected to descriptive analysis using SPSS 18.0 to identify the most frequent drugs and equipment. Chi-square and t-test were used to evaluate the correlation between the variables. p < 0.05 was considered statistically significant. One hundred and twelve dentists answered the questionnaire. The most available drug and equipment were epinephrine (67%) and single use syringe (81.3%) respectively. Significant correlation was found between degree of education and availability of first group of emergency drugs and between sex and possession of second group of emergency equipment (p < 0.05). Degree of availability of emergency drugs and equipment was moderate to low and training about emergencies should be included in the didactic topics of universities and workshops. Information about emergency drug and equipment would help to manage the unwanted emergency situations.
Full Text Available Objective. To quantify the supply of essential drugs and the fully filled-in prescription level in the Units Specialized in the Treatment of Chronic Diseases (UNEMES-EC in Mexico. Materials and methods. The supply and prescription indicators were measured in 30 of the 86 existing UNEMES-EC. The supply of drugs was recorded using a list of 17 essential drugs related to the treatment of diabetes, hypertension, overweight and obesity. The information on fully filled-in prescriptions was obtained through a questionnaire applied to 1 200 health care users. Results. Only 13.3% of these units showed a complete supply of the 17 essential drugs: Supply levels were higher in units with external drugstore service. 35% of the interviewed patients reported out-of-pocket expenditures in medicines. Conclusion. UNEMES-EC should improve their levels of drug supply and fully filled-in prescriptions to reduce out-of-pocket expenditures.
Protein-protein interactions (PPIs) mediate the transmission and regulation of oncogenic signals that are essential to cellular proliferation and survival, and thus represent potential targets for anti-cancer therapeutic discovery. Despite their significance, there is no method to experimentally disrupt and interrogate the essentiality of individual endogenous PPIs. The ability to computationally predict or infer PPI essentiality would help prioritize PPIs for drug discovery and help advance understanding of cancer biology.
Weiner, Scott G; Griggs, Christopher A; Mitchell, Patricia M; Langlois, Breanne K; Friedman, Franklin D; Moore, Rebecca L; Lin, Shuo Cheng; Nelson, Kerrie P; Feldman, James A
We compare emergency provider impression of drug-seeking behavior with objective criteria from a state prescription drug monitoring program, assess change in opioid pain reliever prescribing after prescription drug monitoring program review, and examine clinical factors associated with suspected drug-seeking behavior. This was a prospective observational study of emergency providers assessing a convenience sample of patients aged 18 to 64 years who presented to either of 2 academic medical centers with chief complaint of back pain, dental pain, or headache. Drug-seeking behavior was objectively defined as present when a patient had greater than or equal to 4 opioid prescriptions by greater than or equal to 4 providers in the 12 months before emergency department evaluation. Emergency providers completed data forms recording their impression of the likelihood of drug-seeking behavior, patient characteristics, and plan for prescribing pre- and post-prescription drug monitoring program review. Descriptive statistics were generated. We calculated agreement between emergency provider impression of drug-seeking behavior and prescription drug monitoring program definition, and sensitivity, specificity, and positive predictive value of emergency provider impression, using prescription drug monitoring program criteria as the criterion standard. A multivariate logistic regression analysis was conducted to determine clinical factors associated with drug-seeking behavior. Thirty-eight emergency providers with prescription drug monitoring program access participated. There were 544 patient visits entered into the study from June 2011 to January 2013. There was fair agreement between emergency provider impression of drug-seeking behavior and prescription drug monitoring program (κ=0.30). Emergency providers had sensitivity 63.2% (95% confidence interval [CI] 54.8% to 71.7%), specificity 72.7% (95% CI 68.4% to 77.0%), and positive predictive value 41.2% (95% CI 34.4% to 48
Hofman, S.; Segers, M.M.; Ghimire, S.; Bolhuis, M.S.; Sturkenboom, M.G.; Soolingen, D. van; Alffenaar, J.W.
INTRODUCTION: Tuberculosis (TB) remains a global health problem. Drug resistance, treatment duration, complexity, and adverse drug reactions associated with anti-TB regimens are associated with treatment failure, prolonged infectiousness and relapse. With the current set of anti-TB drugs the goal to
Hofman, S.; Segers, M. M.; Ghimire, S.; Bolhuis, M. S.; Sturkenboom, M. G. G.; Van Soolingen, D.; Alffenaar, J. W. C.
Introduction: Tuberculosis (TB) remains a global health problem. Drug resistance, treatment duration, complexity, and adverse drug reactions associated with anti-TB regimens are associated with treatment failure, prolonged infectiousness and relapse. With the current set of anti-TB drugs the goal to
Full Text Available Pathogens that evolve resistance to drugs usually have reduced fitness. However, mutations that largely compensate for this reduction in fitness often arise. We investigate how these compensatory mutations affect population-wide resistance emergence as a function of drug treatment. Using a model of gonorrhea transmission dynamics, we obtain generally applicable, qualitative results that show how compensatory mutations lead to more likely and faster resistance emergence. We further show that resistance emergence depends on the level of drug use in a strongly nonlinear fashion. We also discuss what data need to be obtained to allow future quantitative predictions of resistance emergence.
Tang, Magdalene H Y; Ching, C K; Tse, M L; Ng, Carol; Lee, Caroline; Chong, Y K; Wong, Watson; Mak, Tony W L
To validate a locally developed chromatography-based method to monitor emerging drugs of abuse whilst performing regular drug testing in abusers. Cross-sectional study. Eleven regional hospitals, seven social service units, and a tertiary level clinical toxicology laboratory in Hong Kong. A total of 972 drug abusers and high-risk individuals were recruited from acute, rehabilitation, and high-risk settings between 1 November 2011 and 31 July 2013. A subset of the participants was of South Asian ethnicity. In total, 2000 urine or hair specimens were collected. Proof of concept that surveillance of emerging drugs of abuse can be performed whilst conducting routine drug of abuse testing in patients. The method was successfully applied to 2000 samples with three emerging drugs of abuse detected in five samples: PMMA (paramethoxymethamphetamine), TFMPP [1-(3-trifluoromethylphenyl)piperazine], and methcathinone. The method also detected conventional drugs of abuse, with codeine, methadone, heroin, methamphetamine, and ketamine being the most frequently detected drugs. Other findings included the observation that South Asians had significantly higher rates of using opiates such as heroin, methadone, and codeine; and that ketamine and cocaine had significantly higher detection rates in acute subjects compared with the rehabilitation population. This locally developed analytical method is a valid tool for simultaneous surveillance of emerging drugs of abuse and routine drug monitoring of patients at minimal additional cost and effort. Continued, proactive surveillance and early identification of emerging drugs will facilitate prompt clinical, social, and legislative management.
Liu, Zhihong; Wang, Yutao; Zhang, Na
During the past decades, polymer-drug conjugates are one of the hottest topics in novel drug development fields. Amphiphilic polymer-drug conjugates in aqueous solution could form micelles or micelle-like nanoassemblies. Compared with polymer-drug conjugates and the micelles into which drugs are physically entrapped, micelles or micelle-like nanoassemblies based on polymer-drug conjugates bring several additional advantages, including increased drug-loading capacity, enhanced intracellular uptake, reduced systemic toxicity, and improved therapeutic efficacy. This review focuses on recent progress achieved in the research field of micelles or micelle-like nanoassemblies based on polymer-drug conjugates. Firstly, properties of polymers, drugs, and linkers which could be used to build polymer-drug conjugate micelles or micelle-like nanoassemblies are summarized. Then, the characterization methods are described. Finally, the drug-targeting mechanisms are discussed. Micelles or micelle-like nanoassemblies based on polymer-drug conjugates as an emerging platform have the potential to achieve medical treatments with enhanced therapeutic effect. The application of micelles or micelle-like nanoassemblies based on polymer-drug conjugates may give new life to old active compounds abandoned due to their low solubility problems. For clinical application, there is a need to further optimize the properties of the polymer, drug, and linker.
Most of the highly abused drugs were 'kuber, shisha, shashaman, mau, tambuu, jet fuel, kukumanga, mkorogo, mshomoro, rohypnol, Artaine and kamusi. 'Shisha' and 'kuber' were most commonly abused drugs in both counties. Over 25% of the shisha and kuber abusers aged between 26 to 35 years. The emerging drugs ...
Clingan, Sarah E; Woodruff, Susan I
Medical care in the emergency department (ED) is a growing and complex area of outpatient care, with about 256 visits made to EDs every minute in 2013. Studies report that, compared to people who do not use drugs, people who use illicit drugs are more likely to use the ED for their medical care. Self-efficacy has been shown to be a predictor of abstinence or reduced use among drug-using individuals. The current study describes drug avoidance self-efficacy among exclusive cannabis-using individuals and other drug-using individuals who use the ED for any reason. Participants were 693 adult patients visiting the trauma units and EDs of two large urban "safety net" hospitals (i.e., providing care to low-income, uninsured, and vulnerable population) in Southern California who reported using illicit drugs in the past 30 days. For people who use only cannabis, higher drug-avoidance self-efficacy was associated with older age, lower drug involvement scores, lower drug severity scores, and higher readiness to change use. For people who use other drugs, higher drug avoidance self-efficacy scores was associated with lower drug severity scores, lower psychiatric severity scores, higher medical severity scores, and higher readiness to change use. This study identified several factors (some common, some unique) related to higher drug-avoidance self-efficacy for both groups. Results may be important when designing intervention protocols for use in the ED.
Purpose: To study the prevalence of resistant strains of S. aureus isolated from surfaces, beds and various equipment of an Iranian hospital emergency ward. Methods: Two hundred swab samples were collected from the surfaces, beds, trolleys, surgical equipment and diagnostic medical devices in emergency ward.
Ulker, Zeynep; Erkey, Can
Over the past few decades, advances in "aerogel science" have provoked an increasing interest for these materials in pharmaceutical sciences for drug delivery applications. Because of their high surface areas, high porosities and open pore structures which can be tuned and controlled by manipulation of synthesis conditions, nanostructured aerogels represent a promising class of materials for delivery of various drugs as well as enzymes and proteins. Along with biocompatible inorganic aerogels and biodegradable organic aerogels, more complex systems such as surface functionalized aerogels, composite aerogels and layered aerogels have also been under development and possess huge potential. Emphasis is given to the details of the aerogel synthesis and drug loading methods as well as the influence of synthesis parameters and loading methods on the adsorption and release of the drugs. Owing to their ability to increase the bioavailability of low solubility drugs, to improve both their stability and their release kinetics, there are an increasing number of research articles concerning aerogels in different drug delivery applications. This review presents an up to date overview of the advances in all kinds of aerogel based drug delivery systems which are currently under investigation. Copyright © 2014 Elsevier B.V. All rights reserved.
Full Text Available Polymeric nanomaterials have the potential to improve upon present chemotherapy delivery methods. They successfully reduce side effects while increasing dosage, increase residence time in the body, offer a sustained and tunable release, and have the ability to deliver multiple drugs in one carrier. However, traditional nanomaterial formulations have not produced highly therapeutic formulations to date due to their passive delivery methods and lack of rapid drug release at their intended site. In this paper, we have focused on a few “smart” technologies that further enhance the benefits of typical nanomaterials. Temperature and pH-responsive drug delivery devices were reviewed as methods for triggering release of encapsulating drugs, while aptamer and ligand conjugation were discussed as methods for targeted and intracellular delivery, with emphases on in vitro and in vivo works for each method.
Bhattacharya, Shiv Sankar; Mishra, Arun Kumar; Verma, Navneet; Verma, Anurag; Pandit, Jayanta Kumar
During recent years carbon nanotubes (CNTs) have been attracted by many researchers as a drug delivery carrier. CNTs are the third allotropic form of carbon-fullerenes which were rolled into cylindrical tubes. To be integrated into the biological systems, CNTs can be chemically modified or functionalised with therapeutically active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Owing to their high carrying capacity, biocompatibility, and specificity to cells, various cancer cells have been explored with CNTs for evaluation of pharmacokinetic parameters, cell viability, cytotoxicty, and drug delivery in tumor cells. This review attempts to highlight all aspects of CNTs which render them as an effective anticancer drug carrier and imaging agent. Also the potential application of CNT in targeting metastatic cancer cells by entrapping biomolecules and anticancer drugs has been covered in this review. PMID:24872894
Brewer, E.; Coleman, J.; Lowman, A.
Polymeric nanomaterials have the potential to improve upon present chemotherapy delivery methods. They successfully reduce side effects while increasing dosage, increase residence time in the body, offer a sustained and tunable release, and have the ability to deliver multiple drugs in one carrier. However, traditional nanomaterial formulations have not produced highly therapeutic formulations to date due to their passive delivery methods and lack of rapid drug release at their intended site. In this paper, we have focused on a few smart technologies that further enhance the benefits of typical nanomaterials. Temperature and pH-responsive drug delivery devices were reviewed as methods for triggering release of encapsulating drugs, while aptamer and ligand conjugation were discussed as methods for targeted and intracellular delivery, with emphases on in vitro and in vivo works for each method.
Dhote, Vinod; Bhatnagar, Punit; Mishra, Pradyumna K.; Mahajan, Suresh C.; Mishra, Dinesh K.
The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drug delivery system together with factors affecting the system. This delivery system utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application. PMID:22396901
Office of National Drug Control Policy, 2007
This report synthesizes a number of national studies that show the intentional abuse of prescription drugs to get high is a growing concern, particularly among teens. The analysis shows that teens are turning away from street drugs and using prescription drugs to get high. New users of prescription drugs have caught up with new users of marijuana.…
Murphy, A P
Facial trauma is a commonly encountered presentation to emergency departments. When associated airway compromise occurs, co-existing head and neck injuries serve to produce a challenging clinical situation. We describe two patients who suffered multi-system trauma, with severe maxillofacial injuries that necessitated prompt definitive airway management and mid-face stabilisation in the pre-hospital and emergency department phases of resuscitation. The McKesson prop is a simple yet highly effective tool for use in these injuries.
Jul 30, 2013 ... Emerging psychoactive substances e.g. morphine, carnabinoids, cathinones ... Results: The drug initiation age ranged from 5 to 28 years though most started ...... and psychological health problems and their drain on health.
Conclusions: The antimicrobial activities of the essential oils are influenced by the strain origin (wild, reference, drug sensitive or resistant and it should be taken into consideration whenever investigating the plants’ potential for developing new antimicrobials. [J Complement Med Res 2016; 5(3.000: 212-218
Theodosiou, Maria; Amir-Aslani, Arsia; Mégarbane, Bruno
Regardless of stringent safety regulations and increased compound selectivity by pharmaceutical companies, prediction of toxicity in humans is still far from perfect and adverse drug reactions are still detected after drug marketing. High costs of failures due to toxicity has led pharmaceutical companies to search for screening methods that would allow detection of toxicity issues at an early stage and improve their preclinical and clinical toxicology. Thanks to the last decade's biotechnology revolution, new technologies like toxicogenomics have demonstrated the capacity to improve toxicity assessment. However, our understanding of toxicological mechanisms is still incomplete and a wide range of approaches must be used to gain insight into toxicity issues. Consequently, an array of in silico, in vitro and in vivo methods is utilized to predict toxicity and its causative mechanisms, improving drug development processes and minimizing costs of failure.
Wagner, Jeffrey R; Lee, Christopher T; Durrant, Jacob D; Malmstrom, Robert D; Feher, Victoria A; Amaro, Rommie E
Allosteric drug development holds promise for delivering medicines that are more selective and less toxic than those that target orthosteric sites. To date, the discovery of allosteric binding sites and lead compounds has been mostly serendipitous, achieved through high-throughput screening. Over the past decade, structural data has become more readily available for larger protein systems and more membrane protein classes (e.g., GPCRs and ion channels), which are common allosteric drug targets. In parallel, improved simulation methods now provide better atomistic understanding of the protein dynamics and cooperative motions that are critical to allosteric mechanisms. As a result of these advances, the field of predictive allosteric drug development is now on the cusp of a new era of rational structure-based computational methods. Here, we review algorithms that predict allosteric sites based on sequence data and molecular dynamics simulations, describe tools that assess the druggability of these pockets, and discuss how Markov state models and topology analyses provide insight into the relationship between protein dynamics and allosteric drug binding. In each section, we first provide an overview of the various method classes before describing relevant algorithms and software packages.
Full Text Available Pharmaceutical scientists throughout the world are trying to explore thin films as a novel drug delivery tool. Thin films have been identified as an alternative approach to conventional dosage forms. The thin films are considered to be convenient to swallow, self-administrable, and fast dissolving dosage form, all of which make it as a versatile platform for drug delivery. This delivery system has been used for both systemic and local action via several routes such as oral, buccal, sublingual, ocular, and transdermal routes. The design of efficient thin films requires a comprehensive knowledge of the pharmacological and pharmaceutical properties of drugs and polymers along with an appropriate selection of manufacturing processes. Therefore, the aim of this review is to provide an overview of the critical factors affecting the formulation of thin films, including the physico-chemical properties of polymers and drugs, anatomical and physiological constraints, as well as the characterization methods and quality specifications to circumvent the difficulties associated with formulation design. It also highlights the recent trends and perspectives to develop thin film products by various companies.
Steckelings, Ulrike Muscha; Paulis, Ludovit; Unger, Thomas; Bader, Michael
The renin-angiotensin-aldosterone system (RAAS) is already the most important target for drugs in the cardiovascular system. However, still new developments are underway to interfere with the system on different levels. The novel strategies to interfere with RAAS aim to reduce the synthesis of the two major RAAS effector hormones, angiotensin (Ang) II and aldosterone, or interfere with their receptors, AT1 and mineralocorticoid receptor, respectively. Moreover, novel targets have been identified in RAAS, such as the (pro)renin receptor, and molecules, which counteract the classical actions of Ang II and are therefore beneficial in cardiovascular diseases. These include the AT2 receptor and the ACE2/Ang-(1-7)/Mas axis. The search for drugs activating these tissue-protective arms of RAAS is therefore the most innovative field in RAAS pharmacology. Most of the novel pharmacological strategies to inhibit the classical RAAS need to prove their superiority above the existing treatment in clinical trials and then have to compete against these now quite cheap drugs in a competitive market. The newly discovered targets have functions beyond the cardiovascular system opening up novel therapeutic areas for drugs interfering with RAAS components.
Thiago Gatti Pianca
Conclusion: The diagnosis and treatment of intoxication by alcohol and other drugs in adolescents and children in the emergency scenario requires a systematic evaluation of the use of these drugs. There are few specific treatments for intoxication, and the management comprehends support measures and management of related clinical complications.
Peak, Taylor C; Yafi, Faysal A; Sangkum, Premsant; Hellstrom, Wayne J G
Erectile dysfunction adversely affects the lives of millions of men, and is the most commonly treated sexual disorder today. The erectile process has been extensively investigated, with major advances made in elucidating many of the complex molecular pathways involved. These advances have allowed researchers to design and study drug formulations that target various aspects of this complex process. The initial culmination of this research was the introduction of phosphodiesterase 5-inhibitors. While effective in many patients, they are not satisfactory for all afflicted men. As a result, researchers are developing novel drugs that target different molecular pathways. The paper will review these pathways, and the potential agents that target them. More specifically, first dopaminergic and melanocortin receptor agonists that act centrally will be covered. Then, the paper will examine the "second-generation" phosphodiesterase 5-inhibitors, soluble guanylate cyclases, rho-kinase inhibitors, and maxi-k channel activators that act peripherally. Most of these novel drugs have yet to reach Phase III studies. However, it is likely that in years to come, patients will be selectively treated with these novel agents as a monotherapy or in combination with others acting in a synergistic manner.
Islam, Nazrul; Richard, Derek
Local delivery of drug to the target organ via inhalation offers enormous benefits in the management of many diseases. Lung cancer is the most common of all cancers and it is the leading cause of death worldwide. Currently available treatment systems (intravenous or oral drug delivery) are not efficient in accumulating the delivered drug into the target tumor cells and are usually associated with various systemic and dose-related adverse effects. The pulmonary drug delivery technology would enable preferential accumulation of drug within the cancer cell and thus be superior to intravenous and oral delivery in reducing cancer cell proliferation and minimising the systemic adverse effects. Site-specific drug delivery via inhalation for the treatment of lung cancer is both feasible and efficient. The inhaled drug delivery system is non-invasive, produces high bioavailability at low dose and avoids first pass metabolism of the delivered drug. Various anticancer drugs including chemotherapeutics, proteins and genes have been investigated for inhalation in lung cancers with significant outcomes. Pulmonary delivery of drugs from dry powder inhaler (DPI) formulation is stable and has high patient compliance. Herein, we report the potential of pulmonary drug delivery from dry powder inhaler (DPI) formulations inhibiting lung cancer cell proliferation at very low dose with reduced unwanted adverse effects. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Mohamed Nadjib Boukhatem
Full Text Available Background: Volatile oils obtained from lemon grass [Cymbopogon citratus (DC. Stapf, Poaceae family] are used in traditional medicine as remedies for the treatment of various diseases. Aims: In the present study, lemon grass essential oil (LGEO was evaluated for its in vivo topical and oral anti-inflammatory effects, and for its in vitro antifungal activity using both liquid and vapor phases. Methods: The chemical profile of LGEO as determined by gas chromatography–mass spectrometry analysis revealed two major components: geranial (42.2%, and neral (31.5%. The antifungal activity of LGEO was evaluated against several pathogenic yeasts and filamentous fungi using disc diffusion and vapor diffusion methods. Results: LGEO exhibited promising antifungal effect against Candida albicans, C. tropicalis, and Aspergillus niger, with different inhibition zone diameters (IZDs (35–90 mm. IZD increased with increasing oil volume. Significantly, higher anti-Candida activity was observed in the vapor phase. For the evaluation of the anti-inflammatory effect, LGEO (10 mg/kg, administered orally significantly reduced carrageenan-induced paw edema with a similar effect to that observed for oral diclofenac (50 mg/kg, which was used as the positive control. Oral administration of LGEO showed dose-dependent anti-inflammatory activity. In addition, topical application of LGEO in vivo resulted in a potent anti-inflammatory effect, as demonstrated by using the mouse model of croton oil-induced ear edema. To our knowledge, this is the first such report to be published. The topical application of LGEO at doses of 5 and 10 µL/ear significantly reduced acute ear edema induced by croton oil in 62.5 and 75% of the mice, respectively. In addition, histological analysis clearly confirmed that LGEO inhibits the skin inflammatory response in animal models. Conclusion: Results of the present study indicate that LGEO has a noteworthy potential for the development of drugs for
Hock, Rebecca S; Hindin, Michelle J; Bass, Judith K; Surkan, Pamela J; Bradshaw, Catherine P; Mendelson, Tamar
Parenting style is a potent and malleable influence on emerging adult substance use. Most of the parenting-substance use literature has been conducted in Western populations and it is unknown whether findings are generalizable to other cultures and contexts. We extended the parenting-substance use literature to a cohort of emerging adults in the Philippines using the Cebu Longitudinal Health and Nutrition Survey. We assessed associations between mothers' and fathers' parenting styles (authoritative, permissive, authoritarian, and neglectful) reported by offspring at age 18 and odds of offspring-reported drug use three years later, adjusted for a range of offspring- and parent/household-level characteristics. Females were dropped from analyses due to low prevalence of drug users. We found that many emerging adults in Cebu reported having used drugs, particularly methamphetamine-a dangerous drug with high abuse potential. Authoritative (warm, firm) mothering was significantly associated with sons' reduced odds of drug use and neglectful fathering was related at a trend level with sons' increased odds of having tried drugs. Findings underscore the relation of parenting styles to emerging adults' drug use and add to the literature on cross-cultural variability in parenting styles.
This article attempts to demonstrate and illustrate important relationships between the concept of the independent economic regulator and the evolution of emerging nation electric power sectors from patterns of government dominance that have undermined both their efficiency and their receptivity to substantial private sector involvement. It re-emphasizes the important relationships between industry structure, competition, market mechanisms and regulation; and the important distinctions between the different roles government can and should play in the power sector in different stages of evolution -as owner, manager, regulator and political policy maker. It seeks to put content and meaning into the concept of the independent regulator in the broader context of power sector reform. It distills from the experience of those countries with developed regulatory systems a series of practical guidelines or principles that may be helpful in the design and implementation of regulatory regimes for electricity and other infrastructural industries in emerging nations in the process of transformation from government dominated monopolies. (author)
Raúl E. Molina-Salazar
Full Text Available Para la Organización Mundial de la Salud (OMS la accesibilidad y la disponibilidad de los medicamentos es un tema central al cual le ha dedicado una gran atención. Si bien la política de medicamentos esenciales ha tenido una acogida favorable por parte de las organizaciones sanitarias, la industria farmacéutica, especialmente sus filiales asentadas en los países menos desarrollados, no ha brindado una respuesta adecuada a los planteamientos de la OMS de proporcionar medicamentos esenciales a precios accesibles. El objetivo de este trabajo es estudiar el precio de los medicamentos esenciales de marca en México en relación al precio de los medicamentos esenciales genéricos disponibles en el mercado internacional. Se estudió una muestra de especialidades farmacéuticas líderes de ventas en su categoría terapéutica y se compararon los precios, por unidades farmacéuticas, de los medicamentos de marca y los medicamentos genéricos a precio internacional. Los resultados muestran que el nivel de precios de los medicamentos esenciales en México es muy elevado. La venta per cápita no se ha reducido, a pesar de la caída del producto interno bruto que se produjo en México a partir del año de 1995. Se discuten las razones de este sobreprecio y se proponen algunas medidas para solucionar este problema.Accessibility and availability of drugs has been a matter of great concern for health services all over the world, especially for less developed countries. The World Health Organization has devoted considerable time to this matter. Although the essential drug policy has been well-accepted by health agencies and NGOs, the pharmaceutical industry has not proven willing to produce essential drugs at affordable prices. The purpose of this study is to examine price levels of essential drugs in Mexico. The evaluation was performed through a comparison of international and national prices for leading drugs in the respective therapeutic categories and
Michael A. Partridge
Full Text Available Anti-drug antibodies induced by biologic therapeutics often impact drug pharmacokinetics, pharmacodynamics response, clinical efficacy, and patient safety. It is critical to assess the immunogenicity risk of potential biotherapeutics in producing neutralizing and nonneutralizing anti-drug antibodies, especially in clinical phases of drug development. Different assay methodologies have been used to detect all anti-drug antibodies, including ELISA, radioimmunoassay, surface plasmon resonance, and electrochemiluminescence-based technologies. The most commonly used method is a bridging assay, performed in an ELISA or on the Meso Scale Discovery platform. In this report, we aim to review the emerging new assay technologies that can complement or address challenges associated with the bridging assay format in screening and confirmation of ADAs. We also summarize generic anti-drug antibody assays that do not require drug-specific reagents for nonclinical studies. These generic assays significantly reduce assay development efforts and, therefore, shorten the assay readiness timeline.
Parhi, Priyambada; Mohanty, Chandana; Sahoo, Sanjeeb Kumar
Combination therapy for the treatment of cancer is becoming more popular because it generates synergistic anticancer effects, reduces individual drug-related toxicity and suppresses multi-drug resistance through different mechanisms of action. In recent years, nanotechnology-based combination drug delivery to tumor tissues has emerged as an effective strategy by overcoming many biological, biophysical and biomedical barriers that the body stages against successful delivery of anticancer drugs. The sustained, controlled and targeted delivery of chemotherapeutic drugs in a combination approach enhanced therapeutic anticancer effects with reduced drug-associated side effects. In this article, we have reviewed the scope of various nanotechnology-based combination drug delivery approaches and also summarized the current perspective and challenges facing the successful treatment of cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.
Iram Khan Iqbal
Full Text Available Mycobacterium tuberculosis (Mtb exhibits remarkable metabolic flexibility that enables it to survive a plethora of host environments during its life cycle. With the advent of bedaquiline for treatment of multidrug-resistant tuberculosis, oxidative phosphorylation has been validated as an important target and a vulnerable component of mycobacterial metabolism. Exploiting the dependence of Mtb on oxidative phosphorylation for energy production, several components of this pathway have been targeted for the development of new antimycobacterial agents. This includes targeting NADH dehydrogenase by phenothiazine derivatives, menaquinone biosynthesis by DG70 and other compounds, terminal oxidase by imidazopyridine amides and ATP synthase by diarylquinolines. Importantly, oxidative phosphorylation also plays a critical role in the survival of persisters. Thus, inhibitors of oxidative phosphorylation can synergize with frontline TB drugs to shorten the course of treatment. In this review, we discuss the oxidative phosphorylation pathway and development of its inhibitors in detail.
Iqbal, Iram Khan; Bajeli, Sapna; Akela, Ajit Kumar
Mycobacterium tuberculosis (Mtb) exhibits remarkable metabolic flexibility that enables it to survive a plethora of host environments during its life cycle. With the advent of bedaquiline for treatment of multidrug-resistant tuberculosis, oxidative phosphorylation has been validated as an important target and a vulnerable component of mycobacterial metabolism. Exploiting the dependence of Mtb on oxidative phosphorylation for energy production, several components of this pathway have been targeted for the development of new antimycobacterial agents. This includes targeting NADH dehydrogenase by phenothiazine derivatives, menaquinone biosynthesis by DG70 and other compounds, terminal oxidase by imidazopyridine amides and ATP synthase by diarylquinolines. Importantly, oxidative phosphorylation also plays a critical role in the survival of persisters. Thus, inhibitors of oxidative phosphorylation can synergize with frontline TB drugs to shorten the course of treatment. In this review, we discuss the oxidative phosphorylation pathway and development of its inhibitors in detail. PMID:29473841
Salach, R H; Cash, J M
The recently recognized high morbidity and unexpected mortality associated with rheumatoid arthritis (RA) has spurred new interest in more aggressive, early treatment of this disease. Methotrexate (MTX) has rapidly become the rheumatologist's drug of choice for serious RA because of its favorable efficacy to toxicity ratio and rapid onset of action compared with other second-line agents. The initial concerns about hepatic fibrosis and cirrhosis in psoriatic patients has subsided somewhat as long-term liver toxicity data are accumulating in patients with RA. Routine liver biopsy with incremental doses of MTX is no longer recommended. Potential for severe lung, hematologic, and infectious complications exists, mandating careful monitoring of RA patients taking MTX.
Khan, M.A.; Smego Jr, R.A.; Razi, S.T.; Beg, M.A.
The increasing prevalence of multi-resistant Plasmodium falciparum malaria worldwide is a serious public health threat to the global control of malaria, especially in poor countries like Pakistan. In many countries chloroquine-resistance is a huge problem, accounting for more than 90% of malaria cases. In Pakistan, resistance to chloroquine is on the rise and reported in up to 16- 62% of Plasmodium falciparum. Four to 25% of Plasmodium falciparum also reported to be resistant to sulfadoxine-pyrimethamine and several cases of delayed parasite clearance have been observed in patients with Plasmodium falciparum malaria treated with quinine. In this article we have introduced the concept of artemisinin- based combination therapy (ACT) and emphasize the use of empiric combination therapy for all patients with Plasmodium falciparum malaria to prevent development of drug resistance and to obtain additive and synergistic killing of parasite. (author)
O. G. Smalyuh
Full Text Available The aim of our study was to develop the method for identification and assay of essential oils of mint and turmeric in complex medicinal product in capsule form. Materials and method.The paper used samples of turmeric and mint essential oils and complex drug, in the form of capsules containing oil of peppermint, oil of Curcuma longa, a mixture of extracts sandy everlasting (Helichrysumarenarium (L. Moench, marigold (Caléndulaofficinális L, wild carrot (Daucussarota and Curcuma longa (Curcuma longa. Results and discussion. The structure of the complex drug is dry extract sand everlasting flowers, wild carrot extract of marigold flowers and fruits thick, dry extract of Curcuma longa and essential oils of peppermint and turmeric. According to the research of different samples of peppermint oil, and given the need for its identification and quantification of the finished medicinal product, we have decided to choose menthol as analytical marker. In order to establish the identity of complex drug its main components - Ar- turmeric, α-and β- turmeric, and their total content must meet the quantitative indicators "content turmerics" in the specifications for turmeric oil. Past studies of sample preparation conditions allowed to offer 96% ethanol to extract oil components from the sample; ultrasonic and centrifugation to improve removal of the capsule weight. Cromatographiccharacteristics of substances was obtained by column firm Agilent, HP-Innowax. It has been established that other active pharmaceutical ingredients capsule (placebo did not affect the quantification of the components of essential oils of mint and turmeric. Conclusions. 1. Chromatographic conditions of identification and assay of essential oils of mint and turmeric in a complex drug and optimal conditions for sample preparation and analysis by gas chromatographyhave been studied. 2. Methods for identification and assay of menthol, α-, β- and Ar- turmerics in complex drug based on
Monzote,Lianet; Montalvo,Ana Margarita; Scull,Ramón; Miranda,Migdalia; Abreu,Juan
To date, there are no vaccines against Leishmania, and chemotherapy remains the mainstay for the control of leishmaniasis. The drugs of choice used for leishmaniasis therapy are significantly toxic, expensive and with a growing frequency of refractory infections. Because of these limitations, a combination therapy is the better hope. This work demonstrates that the essential oil from Chenopodium ambrosioides shows a synergic activity after incubation in conjunction with pentamidine against pr...
Full Text Available BACKGROUND: India is an increasingly influential player in the global pharmaceutical market. Key parts of the drug regulatory system are controlled by the states, each of which applies its own standards for enforcement, not always consistent with others. A pilot study was conducted in two major cities in India, Delhi and Chennai, to explore the question/hypothesis/extent of substandard and counterfeit drugs available in the market and to discuss how the Indian state and federal governments could improve drug regulation and more importantly regulatory enforcement to combat these drugs. METHODOLOGY/PRINCIPAL FINDINGS: Random samples of antimalarial, antibiotic, and antimycobacterial drugs were collected from pharmacies in urban and peri-urban areas of Delhi and Chennai, India. Semi-quantitative thin-layer chromatography and disintegration testing were used to measure the concentration of active ingredients against internationally acceptable standards. 12% of all samples tested from Delhi failed either one or both tests, and were substandard. 5% of all samples tested from Chennai failed either one or both tests, and were substandard. Spatial heterogeneity between pharmacies was observed, with some having more or less substandard drugs (30% and 0% respectively, as was product heterogeneity, with some drugs being more or less frequently substandard (12% and 7% respectively. CONCLUSIONS/SIGNIFICANCE: In a study using basic field-deployable techniques of lesser sensitivity rather than the most advanced laboratory-based techniques, the prevalence of substandard drugs in Delhi and Chennai is confirmed to be roughly in accordance with the Indian government's current estimates. However, important spatial and product heterogeneity exists, which suggests that India's substandard drug problem is not ubiquitous, but driven by a subset of manufacturers and pharmacies which thrive in an inadequately regulated environment. It is likely that the drug regulatory
Bate, Roger; Tren, Richard; Mooney, Lorraine; Hess, Kimberly; Mitra, Barun; Debroy, Bibek; Attaran, Amir
Background India is an increasingly influential player in the global pharmaceutical market. Key parts of the drug regulatory system are controlled by the states, each of which applies its own standards for enforcement, not always consistent with others. A pilot study was conducted in two major cities in India, Delhi and Chennai, to explore the question/hypothesis/extent of substandard and counterfeit drugs available in the market and to discuss how the Indian state and federal governments could improve drug regulation and more importantly regulatory enforcement to combat these drugs. Methodology/Principal Findings Random samples of antimalarial, antibiotic, and antimycobacterial drugs were collected from pharmacies in urban and peri-urban areas of Delhi and Chennai, India. Semi-quantitative thin-layer chromatography and disintegration testing were used to measure the concentration of active ingredients against internationally acceptable standards. 12% of all samples tested from Delhi failed either one or both tests, and were substandard. 5% of all samples tested from Chennai failed either one or both tests, and were substandard. Spatial heterogeneity between pharmacies was observed, with some having more or less substandard drugs (30% and 0% respectively), as was product heterogeneity, with some drugs being more or less frequently substandard (12% and 7% respectively). Conclusions/Significance In a study using basic field-deployable techniques of lesser sensitivity rather than the most advanced laboratory-based techniques, the prevalence of substandard drugs in Delhi and Chennai is confirmed to be roughly in accordance with the Indian government's current estimates. However, important spatial and product heterogeneity exists, which suggests that India's substandard drug problem is not ubiquitous, but driven by a subset of manufacturers and pharmacies which thrive in an inadequately regulated environment. It is likely that the drug regulatory system in India needs
Full Text Available Magalie Paillet-Loilier,1 Alexandre Cesbron,1 Reynald Le Boisselier,2 Joanna Bourgine,1 Danièle Debruyne1,2 1Toxicology and Pharmacology Laboratory, 2Centre d'Evaluation et d'Information sur la Pharmacodépendance – Addictovigilance (CEIP-A, Department of Pharmacology, University Hospital Centre, Caen, France Abstract: Substituted cathinones are synthetic analogs of cathinone that can be considered as derivatives of phenethylamines with a beta-keto group on the side chain. They appeared in the recreational drug market in the mid-2000s and now represent a large class of new popular drugs of abuse. Initially considered as legal highs, their legal status is variable by country and is rapidly changing, with government institutions encouraging their control. Some cathinones (such as diethylpropion or pyrovalerone have been used in a medical setting and bupropion is actually indicated for smoking cessation. Substituted cathinones are widely available from internet websites, retail shops, and street dealers. They can be sold under chemical, evocative or generic names, making their identification difficult. Fortunately, analytical methods have been developed in recent years to solve this problem. Available as powders, substituted cathinones are self-administered by snorting, oral injestion, or intravenous injection. They act as central nervous system stimulants by causing the release of catecholamines (dopamine, noradrenaline, and serotonin and blocking their reuptake in the central and peripheral nervous system. They may also decrease dopamine and serotonin transporter function as nonselective substrates or potent blockers and may inhibit monoamine oxidase effects. Nevertheless, considerable differences have been found in the potencies of the different substituted cathinones in vitro. Desired effects reported by users include increased energy, empathy, and improved libido. Cardiovascular (tachycardia, hypertension and psychiatric
Weegmann, Martin; Khantzian, Edward J
Contemporary psychodynamic therapists, as contrasted with early ones, are more active and interactive, less dependent on interpretations, and more focused on affects, self-regulation, and interpersonal relations, with a premium placed on the therapeutic alliance. Evidence supports the utility and effectiveness of the psychodynamic paradigm. Two cases are presented that demonstrate how a well-trained psychodynamic therapist is able to effectively apply such an approach to individuals with substance use disorders, in one instance a client in early treatment still immersed in her addictions, and, in the second case a client in early abstinence emerging from a long standing dependency on alcohol and cocaine. The case material highlights the special sensitivities and practices required to address predisposing factors and resulting consequences associated with addictive disorders. Reflections by the therapist and the clients provide a basis to consider the nature of the clients' addictive involvements, a rationale for the therapist's interventions, and how client vulnerabilities are addressed in their attempts to recover from their addictions.
Adams, Sean H.
Dysregulation of insulin action is most often considered in the context of impaired glucose homeostasis, with the defining feature of diabetes mellitus being elevated blood glucose concentration. Complications arising from the hyperglycemia accompanying frank diabetes are well known and epidemiological studies point to higher risk toward development of metabolic disease in persons with impaired glucose tolerance. Although the central role of proper blood sugar control in maintaining metabolic health is well established, recent developments have begun to shed light on associations between compromised insulin action [obesity, prediabetes, and type 2 diabetes mellitus (T2DM)] and altered intermediary metabolism of fats and amino acids. For amino acids, changes in blood concentrations of select essential amino acids and their derivatives, in particular BCAA, sulfur amino acids, tyrosine, and phenylalanine, are apparent with obesity and insulin resistance, often before the onset of clinically diagnosed T2DM. This review provides an overview of these changes and places recent observations from metabolomics research into the context of historical reports in the areas of biochemistry and nutritional biology. Based on this synthesis, a model is proposed that links the FFA-rich environment of obesity/insulin resistance and T2DM with diminution of BCAA catabolic enzyme activity, changes in methionine oxidation and cysteine/cystine generation, and tissue redox balance (NADH/NAD+). PMID:22332087
Grzesiak, Barbara; Głowacka, Anna; Krukowski, Henryk; Lisowski, Andrzej; Lassa, Henryka; Sienkiewicz, Monika
The algae of the genus Prototheca are environmental pathogens whose main reservoir is the habitat of cows. They can cause protothecosis in domestic and wild animals, as well as human beings, with the main etiological agents being Prototheca zopfii in animals and Prototheca wickerhamii in humans. The aim of the study was to evaluate the in vitro activity of selected essential oils and antifungal antibiotics against P. zopfii isolates. The material consisted of nine P. zopfii strains isolated from the milk of cows suffering from mastitis. Eight essential oils produced by POLLENA-AROMA, Poland, and nine antifungal agents were tested. The effects of essential oils on P. zopfii were evaluated by microdilution with liquid Sabouraud dextrose broth, and susceptibility to antifungal agents was tested using the disk-diffusion method. All used essential oils inhibited the activity of P. zopfii isolates, with MIC values ranging from 0.2 to 10.5 μl/ml. Cinnamon, clove, and thyme demonstrated the highest activity against the tested P. zopfii strains at concentrations ranging from 0.6 to 1.0 μl/ml. Of the antifungal agents, the tested strains were the most sensitive to nystatin (100 %). The tested essential oils can be used to complement protothecosis therapy in animals and human beings.
Quan, Hui; Chen, Xun; Zhang, Ji; Zhao, Peng-Liang
Paradigm for new drug development has changed dramatically over the last decade. Even though new technology increases efficiency in many aspects, partially due to much more stringent regulatory requirements, it actually now takes longer and costs more to develop a new drug. To deal with challenge, some initiatives are taken by the pharmaceutical industry. These initiatives include exploring emerging markets, conducting global trials and building research and development centers in emerging markets to curb spending. It is particularly the current trend that major pharmaceutical companies offshore a part of their biostatistical support to China. In this paper, we first discuss the skill set for trial statisticians in the new era. We then elaborate on some of the approaches for acquiring statistical talent and capacity in general, particularly in emerging markets. We also make some recommendations on the use of the PDUFA strategy and collaborations among industry, health authority and academia from emerging market statistical perspective. © 2013.
Tsyrulnik, Alina; Landman, Adam B.
Drug rash with eosinophilia and systemic symptoms (DRESS) is a rare, severe adverse drug event that appears with a generalized rash, fevers, and dysfunction of 1 or more organ systems. We describe 2 patients (1 adult and 1 pediatric) seen in the emergency department with DRESS, and review the clinical presentations, potential complications, and management of DRESS. Although rare, it can be associated with significant morbidity, including liver failure and death, and should be considered in th...
Pendhari, Shabbir Rafiq; Chaudhari, Devendra Ramesh; Burute, Shreyas Ramchandra; Bite, Bapurao Motiram
To observe the cardiovascular emergencies which were most frequently treated and to quantify the drug utilization trends in the cardiovascular emergencies, in terms of the Defined Daily Doses [DDD] and the prescribing prevalence in the cardiovascular emergencies. This prescription based study was undertaken in the Medicine ICU of the government medical hospital. The age, sex, diagnosis (only cardiovascular) and the drugs which were prescribed, were recorded for each patient. Also, the brand names and the generic names of the prescribed drugs were noted. The collected data was analyzed to study the drug utilization trends. It was observed that the most commonly treated cardiovascular disease was IHD. The IHD was more in males than in females who were below 50 years of age and it was nearly equal in the age groups which were above 50 years. The use of Angiotensin Converting Enzyme (ACE) inhibitors was higher than that of the beta blockers and the calcium channel blockers. The patients with cardiovascular emergencies also had preceding associated diseases like diabetes mellitus and hypertension. The protocol of the management which was followed by the college in the treatment of cardiovascular emergencies was competent enough, as the clinical outcomes of the patients were favourable. But there was a guideline incongruent prescribing behaviour which was statistically significant, for which there is a need to undertake large scale studies.
This podcast describes the emergence of increasingly drug resistant tuberculosis at a mine in South Africa. CDCâs Dr. Dixie Snider discusses the outbreak and some of the reasons it may have occurred, despite the existence of a well-functioning TB control program at the mine. Created: 3/3/2010 by Emerging Infectious Diseases. Date Released: 3/3/2010.
Harding, Richard; Simms, Victoria; Penfold, Suzanne; Downing, Julia; Powell, Richard A; Mwangi-Powell, Faith; Namisango, Eve; Moreland, Scott; Gikaara, Nancy; Atieno, Mackuline; Kataike, Jennifer; Nsubuga, Clare; Munene, Grace; Banga, Geoffrey; Higginson, Irene J
World Health Organization's essential drugs list can control the highly prevalent HIV-related pain and symptoms. Availability of essential medicines directly influences clinicians' ability to effectively manage distressing manifestations of HIV. To determine the availability of pain and symptom controlling drugs in East Africa within President's Emergency Plan for AIDS Relief-funded HIV health care facilities. Directly observed quantitative health facilities' pharmacy stock review. We measured availability, expiration and stock-outs of specified drugs required for routine HIV management, including the World Health Organization pain ladder. A stratified random sample in 120 President's Emergency Plan for AIDS Relief-funded HIV care facilities (referral and district hospitals, health posts/centres and home-based care providers) in Kenya and Uganda. Non-opioid analgesics (73%) and co-trimoxazole (64%) were the most commonly available drugs and morphine (7%) the least. Drug availability was higher in hospitals and lower in health centres, health posts and home-based care facilities. Facilities generally did not use minimum stock levels, and stock-outs were frequently reported. The most common drugs had each been out of stock in the past 6 months in 47% of facilities stocking them. When a minimum stock level was defined, probability of a stock-out in the previous 6 months was 32.6%, compared to 45.5% when there was no defined minimum stock level (χ (2) = 5.07, p = 0.024). The data demonstrate poor essential drug availability, particularly analgesia, limited by facility type. The lack of strong opioids, isoniazid and paediatric formulations is concerning. Inadequate drug availability prevents implementation of simple clinical pain and symptom control protocols, causing unnecessary distress. Research is needed to identify supply chain mechanisms that lead to these problems.
Millions of people worldwide suffer a range of health and socio-economic related problems because of inadequate availability and use of controlled essential medicines like morphine and codeine for pain treatment. As a result, millions of people, often living in lesser-advanced conditions, suffer in
Shivaraj B Warad
Full Text Available Background: It has been long recognized that periodontal diseases are infections of the periodontium, comprising the bacterial etiology, an immune response, and tissue destruction. Treatment strategies aiming primarily at suppressing or eliminating specific periodontal pathogens include adjunct use of local and systemic antibiotics as part of nonsurgical periodontal therapy. Unwanted side effects and resistance of microorganisms toward antibiotics due to their widespread use have modified the general perception about their efficacy. Research in phytosciences has revealed various medicinal plants offering a new choice of optional antimicrobial therapy. Cymbopogon citratus, Stapf. (lemongrass is a popular medicinal plant. At a concentration ≤2%, lemongrass essential oil inhibits the growth of several kinds of microorganisms including periodontal pathogens, especially the reference strains Actinomyces naeslundii and Porphyromonas gingivalis, which were resistant to tetracycline hydrochloride. Aims: To evaluate the efficacy of locally delivered 2% lemongrass essential oil in gel form as an adjunct to scaling and root planing, as compared to scaling and root planing alone for the treatment of chronic periodontitis. Materials and Methods: 2% Lemongrass essential oil gel was prepared and placed in moderate to deep periodontal pockets after scaling and root planing. Results: Statistically significant reduction in probing depth and gingival index and gain in relative attachment level were noted in the experimental group as compared to the control group at 1 and 3 months. Conclusion: Locally delivered 2% lemongrass essential oil gel offers a new choice of safe and effective adjunct to scaling and root planing in periodontal therapy.
Warad, Shivaraj B.; Kolar, Sahana S.; Kalburgi, Veena; Kalburgi, Nagaraj B.
Background: It has been long recognized that periodontal diseases are infections of the periodontium, comprising the bacterial etiology, an immune response, and tissue destruction. Treatment strategies aiming primarily at suppressing or eliminating specific periodontal pathogens include adjunct use of local and systemic antibiotics as part of nonsurgical periodontal therapy. Unwanted side effects and resistance of microorganisms toward antibiotics due to their widespread use have modified the general perception about their efficacy. Research in phytosciences has revealed various medicinal plants offering a new choice of optional antimicrobial therapy. Cymbopogon citratus, Stapf. (lemongrass) is a popular medicinal plant. At a concentration ≤2%, lemongrass essential oil inhibits the growth of several kinds of microorganisms including periodontal pathogens, especially the reference strains Actinomyces naeslundii and Porphyromonas gingivalis, which were resistant to tetracycline hydrochloride. Aims: To evaluate the efficacy of locally delivered 2% lemongrass essential oil in gel form as an adjunct to scaling and root planing, as compared to scaling and root planing alone for the treatment of chronic periodontitis. Materials and Methods: 2% Lemongrass essential oil gel was prepared and placed in moderate to deep periodontal pockets after scaling and root planing. Results: Statistically significant reduction in probing depth and gingival index and gain in relative attachment level were noted in the experimental group as compared to the control group at 1 and 3 months. Conclusion: Locally delivered 2% lemongrass essential oil gel offers a new choice of safe and effective adjunct to scaling and root planing in periodontal therapy. PMID:24991068
Reyes, J C; Negrón, J L; Colón, H M; Padilla, A M; Millán, M Y; Matos, T D; Robles, R R
During the last decade, the veterinary anesthetics have gained popularity as recreational drugs. The aim of this study was to document the use of "anestecia de caballo" (xylazine) and its consequences among drug users in Puerto Rico. The study combined a cross-sectional survey with 89 drug users and two focus groups conducted in Mayagüez with frontline drug treatment providers. Drug users were recruited from communities of the San Juan metropolitan area using a variety of ethnographic and outreach strategies. A short questionnaire developed for the study collected information on sociodemographics, xylazine use, and its consequences. The two focus groups were conducted to discuss the details related to xylazine use, its consequences, and utilization awareness. The sample comprised 63 males (70.8%) and 26 females with a mean age of 37.2 years. The mean number of years of drug use was 14.3, with a mean frequency of drug use of 5.9 times daily. More than 65% reported speedball as the principal drug of use. The prevalence of xylazine use was 80.7%. More than 42% of the sample used xylazine in a mixture with speedball. The main route of administration of xylazine was injection but 14% reported the use of xylazine by inhalation. More than 35% of the sample reported skin lesions and 21.1% reported at least one overdose episode. Multiple logistic regression analysis revealed that males (OR = 3.47, CI = 1.10-12.00) and those who reported speedball as their main drug of use (OR = 9.34, CI = 2.51-34.70) were significantly more likely to be xylazine users. Focus groups revealed that drug users claimed to recognize the presence of xylaxine in a mixture of speedball based on its effects, taste, the color of the drug (dark brown), and its odor. In conclusion, the use of xylazine among drug users in Puerto Rico seems to be an emerging trend with potentially serious health consequences.
Drs. R. Pandjaitan
Full Text Available National Quality Control Laboratory of Drugs and Food (NQCL DF is a central quality control laboratory for pharmaceuticals and food commodities under the supervision of the Director General of Drug and Food Control, Ministry of Health.Based on the Ministry of Health Act.No. 145/Menkes/SK/IV/1978, in 1978, NQCL DF was established. In the same year 27 Provincial Quality Control Laboratory of Drug and Food (PQCL DF, in each province in Indonesia were also established based on the Ministry of Health Act.No. 146/Menkes/ SK/IV/1978. The objective of NQCL DF are: To protect the consumers from adulterated or misbranded pharmaceutical and food commodities.To evaluated and to accrediate the quality control laboratories of pharmaceuticals and food commoditities.To control and give guidance to all quality control laboratories of drug and food.To stimulate the quality of domestic products of pharmaceuticals and food commodities to promote the volume of exports.
Islam, Nazrul; Abbas, Muzaffar; Rahman, Shafiqur
Neuropathic pain is a chronic neurological disorder affecting millions of people around the world. The currently available pharmacologic agents for the treatment of neuropathic pain have limited efficacy and are associated with dose related unwanted adverse effects. Due to the limited access of drug molecules across blood-brain barrier, a small percentage of drug that is administered systematically, reaches the central nervous system in active form. These therapeutic agents also require daily treatment regimen that is inconvenient and potentially impact patient compliance. Application of nanoparticulate drugs for enhanced delivery system has been explored extensively in the last decades. Pulmonary delivery of nanomedicines for the management of various diseases has become an emerging treatment strategy that ensures the targeted delivery of drugs both for systemic and local effects with low dose and limited adverse effects. To the best of our knowledge, there are no inhaled drug products available on market for the treatment of neuropathic pain. The advantages of delivering therapeutics into deep lungs include non-invasive drug delivery, higher bioavailability with low dose, lower systemic toxicity, and potentially greater blood-brain barrier penetration. This review discusses and highlights the important issues on the application of emerging nanoparticulate lung delivery of drugs for the effective treatment of neuropathic pain. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Dib, Leila; Hayek, Peter; Sadek, Helen; Beyrouthy, Berna; Khalaf, Roy A
Candida albicans is a dimorphic pathogenic fungus that causes mucosal and systemic infections. C. albicans pathogenicity is attributed to its ability to exist in different morphologic states and to respond to stress by up regulating several key genes. DDR48 is a stress-associated gene involved in DNA repair and in response to antifungal drug exposure. One allele of DDR48 was knocked out by homologous recombination that inserted a marker cassette in its position. Furthermore, reintroducing DDR48 on a plasmid created a revertant strain. Strains were grown on filamentation inducing and noninducing media, subjected to an oxidative stress challenge, injected into mice to assess virulence, and assayed for antifungal susceptibility by the E-test method. DDR48 was found to be haploid insufficient and possibly essential, since only a heterozygote, but not a homozygous, null mutant was generated. The mutant was filamentation defective on all hyphal media tested including serum and corn meal agar. Discrepancies in drug resistance profiles also were present: compared with the parental strain, DDR48/ddr48 heterozygote strain was susceptible in a dose-dependent manner to itraconazole and fluconazole and susceptible to ketoconazole. The mutant also appeared to be hypersensitive to a potentially lethal hydrogen peroxide challenge. However, no reduction in virulence of the mutant was observed. The present findings provide evidence that DDR48 is essential for filamentation, stress response, and possibly viability of C. albicans, making it a prime target for antifungal drug design.
Full Text Available Despite explicitly wanting to quit, long-term addicts find themselves powerless to resist drugs, despite knowing that drug-taking may be a harmful course of action. Such inconsistency between the explicit knowledge of negative consequences and the compulsive behavioral patterns represents a cognitive/behavioral conflict that is a central characteristic of addiction. Neurobiologically, differential cue-induced activity in distinct striatal subregions, as well as the dopamine connectivity spiraling from ventral striatal regions to the dorsal regions, play critical roles in compulsive drug seeking. However, the functional mechanism that integrates these neuropharmacological observations with the above-mentioned cognitive/behavioral conflict is unknown. Here we provide a formal computational explanation for the drug-induced cognitive inconsistency that is apparent in the addicts' "self-described mistake". We show that addictive drugs gradually produce a motivational bias toward drug-seeking at low-level habitual decision processes, despite the low abstract cognitive valuation of this behavior. This pathology emerges within the hierarchical reinforcement learning framework when chronic exposure to the drug pharmacologically produces pathologicaly persistent phasic dopamine signals. Thereby the drug hijacks the dopaminergic spirals that cascade the reinforcement signals down the ventro-dorsal cortico-striatal hierarchy. Neurobiologically, our theory accounts for rapid development of drug cue-elicited dopamine efflux in the ventral striatum and a delayed response in the dorsal striatum. Our theory also shows how this response pattern depends critically on the dopamine spiraling circuitry. Behaviorally, our framework explains gradual insensitivity of drug-seeking to drug-associated punishments, the blocking phenomenon for drug outcomes, and the persistent preference for drugs over natural rewards by addicts. The model suggests testable predictions and
The discovery of antibiotics has enabled serious infections to be treated. However, bacteria resistant to several families of antibiotics and the emergence of new highly drug-resistant bacteria constitute a public health issue in France and across the world. Actions to prevent their transmission are being put in place. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
This podcast describes the emergence of increasingly drug resistant tuberculosis at a mine in South Africa. CDCâs Dr. Dixie Snider discusses the outbreak and some of the reasons it may have occurred, despite the existence of a well-functioning TB control program at the mine.
Wallace, Bret D.; Roberts, Adam B.; Pollet, Rebecca M.; Ingle, James D.; Biernat, Kristen A.; Pellock, Samuel J.; Venkatesh, Madhu Kumar; Guthrie, Leah; ONeal, Sara K.; Robinson, Sara J.; Dollinger, Makani; Figueroa, Esteban; McShane, Sarah R.; Cohen, Rachel D.; Jin, Jian; Frye, Stephen V.; Zamboni, William C.; Pepe-Ranney, Charles; Mani, Sridhar; Kelly, Libusha; Redinbo, Matthew (Einstein); (UNC); (Cornell)
The selective inhibition of bacterial β-glucuronidases was recently shown to alleviate drug-induced gastrointestinal toxicity in mice, including the damage caused by the widely used anticancer drug irinotecan. Here, we report crystal structures of representative β-glucuronidases from the Firmicutes Streptococcus agalactiae and Clostridium perfringens and the Proteobacterium Escherichia coli, and the characterization of a β-glucuronidase from the Bacteroidetes Bacteroides fragilis. While largely similar in structure, these enzymes exhibit marked differences in catalytic properties and propensities for inhibition, indicating that the microbiome maintains functional diversity in orthologous enzymes. Small changes in the structure of designed inhibitors can induce significant conformational changes in the β-glucuronidase active site. Finally, we establish that β-glucuronidase inhibition does not alter the serum pharmacokinetics of irinotecan or its metabolites in mice. Together, the data presented advance our in vitro and in vivo understanding of the microbial β-glucuronidases, a promising new set of targets for controlling drug-induced gastrointestinal toxicity.
Raza, A.; Beg, M.A.
Plasmodium (P.) vivax is the prevalent malarial species accounting for 70% of malaria cases in Pakistan. However, baseline epidemiological data on P. vivax population structure and drug resistance are lacking from Pakistan. For population structure studies, molecular genetic markers, circumsporozoite protein (csp) and merozoite surface protein-1 (msp-1) are considered useful as these play an important role in P. vivax survival under immune and environmental pressure. Furthermore, these genes have also been identified as suitable candidates for vaccine development. While efforts for effective vaccine are underway, anti-malarial agents remain the mainstay for control. Evidence of resistance against commonly used anti-malarial agents, particularly Sulphadoxine-Pyrimethamine (SP) is threatening to make this form of control defunct. Therefore, studies on drug resistance are necessary so that anti-malarial treatment strategies can be structured and implemented accordingly by the Malaria Control Program, Pakistan. This review aims to provide information on genetic markers of P. vivax population structure and drug resistance and comment on their usefulness in molecular surveillance and control. (author)
Sikora, Magdalena; Tokarski, Krzysztof; Bobula, Bartosz; Zajdel, Joanna; Jastrzębska, Kamila; Cieślak, Przemysław Eligiusz; Zygmunt, Magdalena; Sowa, Joanna; Smutek, Magdalena; Kamińska, Katarzyna; Gołembiowska, Krystyna; Engblom, David; Hess, Grzegorz; Przewlocki, Ryszard; Rodriguez Parkitna, Jan
Plasticity of the brain's dopamine system plays a crucial role in adaptive behavior by regulating appetitive motivation and the control of reinforcement learning. In this study, we investigated drug- and natural-reward conditioned behaviors in a mouse model in which the NMDA receptor-dependent plasticity of dopaminoceptive neurons was disrupted. We generated a transgenic mouse line with inducible selective inactivation of the NR1 subunit in neurons expressing dopamine D1 receptors (the NR1(D1CreERT2) mice). Whole-cell recordings of spontaneous EPSCs on neurons in the nucleus accumbens confirmed that a population of neurons lacked the NMDA receptor-dependent component of the current. This effect was accompanied by impaired long-term potentiation in the nucleus accumbens and in the CA1 area of the ventral, but not the dorsal, hippocampus. Mutant mice did not differ from control animals when tested for pavlovian or instrumental conditioning. However, NR1(D1CreERT2) mice acquired no preference for a context associated with administration of drugs of abuse. In the conditioned place preference paradigm, mutant mice did not spend more time in the context paired with cocaine, morphine, or ethanol, although these mice acquired a preference for sucrose jelly and an aversion to naloxone injections, as normal. Thus, we observed that the selective inducible ablation of the NMDA receptors specifically blocks drug-associated context memory with no effect on positive reinforcement in general.
Tokarski, Krzysztof; Bobula, Bartosz; Zygmunt, Magdalena; Smutek, Magdalena; Kamińska, Katarzyna; Gołembiowska, Krystyna; Hess, Grzegorz; Przewlocki, Ryszard
Abstract Plasticity of the brain’s dopamine system plays a crucial role in adaptive behavior by regulating appetitive motivation and the control of reinforcement learning. In this study, we investigated drug- and natural-reward conditioned behaviors in a mouse model in which the NMDA receptor-dependent plasticity of dopaminoceptive neurons was disrupted. We generated a transgenic mouse line with inducible selective inactivation of the NR1 subunit in neurons expressing dopamine D1 receptors (the NR1D1CreERT2 mice). Whole-cell recordings of spontaneous EPSCs on neurons in the nucleus accumbens confirmed that a population of neurons lacked the NMDA receptor-dependent component of the current. This effect was accompanied by impaired long-term potentiation in the nucleus accumbens and in the CA1 area of the ventral, but not the dorsal, hippocampus. Mutant mice did not differ from control animals when tested for pavlovian or instrumental conditioning. However, NR1D1CreERT2 mice acquired no preference for a context associated with administration of drugs of abuse. In the conditioned place preference paradigm, mutant mice did not spend more time in the context paired with cocaine, morphine, or ethanol, although these mice acquired a preference for sucrose jelly and an aversion to naloxone injections, as normal. Thus, we observed that the selective inducible ablation of the NMDA receptors specifically blocks drug-associated context memory with no effect on positive reinforcement in general. PMID:27294197
Full Text Available Viroj WiwanitkitWiwanitkit House, Bangkhae, Bangkok 10160Abstract: Influenza is a well known infection of the respiratory system. The main clinical manifestations of influenza include fever, sore throat, headache, cough, coryza, and malaise. Apart from the well known classical influenza, there are also groups of influenza virus infections that are called “atypical infection”. These infections are usually due to a novel influenza virus infection. In early 2009, an emerging novel influenza originating from Mexico called swine flu was reported. The World Health Organization noted a level VI precaution, the highest level precaution possible, for this newest influenza virus infection. As of June 2009, it is not known if this disease will be successfully controlled. Finding new drugs and vaccine for the emerging swine flu is still required to cope with this emerging worldwide problem.Keywords: swine flu, drug, vaccine, concept
Sean M. Curry
Full Text Available Introduction: Drug-seeking behavior (DSB in the emergency department (ED is a very commonproblem, yet there has been little quantitative study to date of such behavior.The goal of this study wasto assess the frequency with which drug seeking patients in the ED use classic drug seeking behaviorsto obtain prescription medication.Methods: We performed a retrospective chart review on patients in an ED case management programfor DSB. We reviewed all visits by patients in the program that occurred during a 1-year period, andrecorded the frequency of the following behaviors: complaining of headache, complaining of backpain, complaining of dental pain, requesting medication by name, requesting a refill of medication,reporting medications as having been lost or stolen, reporting 10/10 pain, reporting greater than 10/10pain, reporting being out of medication, and requesting medication parenterally. These behaviors werechosen because they are described as “classic” for DSB in the existing literature.Results: We studied 178 patients from the case management program, who made 2,486 visits in 1year. The frequency of each behavior was: headache 21.7%, back pain 20.8%, dental pain 1.8%,medication by name 15.2%, requesting refill 7.0%, lost or stolen medication 0.6%, pain 10/10 29.1%,pain greater than 10/10 1.8%, out of medication 9.5%, and requesting parenteral medication 4.3%.Patients averaged 1.1 behaviors per visit.Conclusion: Drug-seeking patients appear to exhibit “classically” described drug-seeking behaviorswith only low to moderate frequency. Reliance on historical features may be inadequate when trying toassess whether or not a patient is drug-seeking.
Lu, Wenjie; Xu, Youzhi; Zhao, Yinglan; Cen, Xiaobo
Drug metabolite identification and metabolic characteristics analysis play a crucial role in new drug research and development, because they can lead to varied efficacy, severe adverse reactions, and even toxicity. Classical methodologies for metabolite identification have mainly been based on mass spectrometry (MS) coupled with gas chromatography (GC) or liquid chromatography (LC), and some other techniques are used as complementary approaches, such as nuclear magnetic resonance (NMR). Over the past decade, more and more newly emerging techniques or technologies have been applied to metabolite identification, and are making the procedure easier and more robust, such as LC-NMR-MS, ion mobility MS, ambient ionization techniques, and imaging MS. A novel application of drug metabolite identification based on "omics" known as pharmacometabonomics is discussed, which is an interdisciplinary field that combines pre-dose metabolite profiling and chemometrics methods for data analysis and modeling, aiming to predict the responses of individuals to drugs.
Kisała, Joanna; Heclik, Kinga I; Pogocki, Krzysztof; Pogocki, Dariusz
The blood-brain barrier (BBB) is a complex system controlling two-way substances traffic between circulatory (cardiovascular) system and central nervous system (CNS). It is almost perfectly crafted to regulate brain homeostasis and to permit selective transport of molecules that are essential for brain function. For potential drug candidates, the CNS-oriented neuropharmaceuticals as well as for those of primary targets in the periphery, the extent to which a substance in the circulation gains access to the CNS seems crucial. With the advent of nanopharmacology the problem of the BBB permeability for drug nano-carriers gains new significance. Compare to some other fields of medicinal chemistry, the computational science of nanodelivery is still prematured to offer the black-box type solutions, especially for the BBB-case. However, even its enormous complexity can be spell out the physical principles, and as such subjected to computation. Basic understanding of various physico-chemical parameters describing the brain uptake is required to take advantage of their usage for the BBB-nanodelivery. This mini-review provides a sketchy introduction into essential concepts allowing application of computational simulation to the BBB-nanodelivery design. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Thiago Gatti Pianca
Full Text Available Abstract Objective: To review the screening, diagnosis, evaluation, and treatment of intoxication by alcohol and other drugs in children and adolescents in the emergency scenario. Data source: This was a narrative literature review. Data summary: The detection of this problem in the emergency room can be a challenge, especially when its assessment is not standardized. The intentional and episodic use of large amounts of psychoactive substances by adolescents is a usual occurrence, and unintentional intoxication is more common in children younger than 12 years. The clinical picture in adolescents and children differs from that in adults and some particularities are important in the emergency scenario. After management of the acute condition, interventions targeting the adolescent at risk may be effective. Conclusion: The diagnosis and treatment of intoxication by alcohol and other drugs in adolescents and children in the emergency scenario requires a systematic evaluation of the use of these drugs. There are few specific treatments for intoxication, and the management comprehends support measures and management of related clinical complications.
Pianca, Thiago Gatti; Sordi, Anne Orgle; Hartmann, Thiago Casarin; von Diemen, Lisia
To review the screening, diagnosis, evaluation, and treatment of intoxication by alcohol and other drugs in children and adolescents in the emergency scenario. This was a narrative literature review. The detection of this problem in the emergency room can be a challenge, especially when its assessment is not standardized. The intentional and episodic use of large amounts of psychoactive substances by adolescents is a usual occurrence, and unintentional intoxication is more common in children younger than 12 years. The clinical picture in adolescents and children differs from that in adults and some particularities are important in the emergency scenario. After management of the acute condition, interventions targeting the adolescent at risk may be effective. The diagnosis and treatment of intoxication by alcohol and other drugs in adolescents and children in the emergency scenario requires a systematic evaluation of the use of these drugs. There are few specific treatments for intoxication, and the management comprehends support measures and management of related clinical complications. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.
Full Text Available Metronomic chemotherapy using cyclophosphamide (CPA is widely associated with antiangiogenesis; however, recent studies implicate other immune-based mechanisms, including antitumor innate immunity, which can induce major tumor regression in implanted brain tumor models. This study demonstrates the critical importance of drug schedule: CPA induced a potent antitumor innate immune response and tumor regression when administered intermittently on a 6-day repeating metronomic schedule but not with the same total exposure to activated CPA administered on an every 3-day schedule or using a daily oral regimen that serves as the basis for many clinical trials of metronomic chemotherapy. Notably, the more frequent metronomic CPA schedules abrogated the antitumor innate immune and therapeutic responses. Further, the innate immune response and antitumor activity both displayed an unusually steep dose-response curve and were not accompanied by antiangiogenesis. The strong recruitment of innate immune cells by the 6-day repeating CPA schedule was not sustained, and tumor regression was abolished, by a moderate (25% reduction in CPA dose. Moreover, an ~20% increase in CPA dose eliminated the partial tumor regression and weak innate immune cell recruitment seen in a subset of the every 6-day treated tumors. Thus, metronomic drug treatment must be at a sufficiently high dose but also sufficiently well spaced in time to induce strong sustained antitumor immune cell recruitment. Many current clinical metronomic chemotherapeutic protocols employ oral daily low-dose schedules that do not meet these requirements, suggesting that they may benefit from optimization designed to maximize antitumor immune responses.
Chen, Isaac Chun-Jen; Hung, Dong-Zong; Hsu, Chi-Ho; Wu, Ming-Ling; Deng, Jou-Fang; Chang, Chin-Yu; Shih, Hsin-Chin; Liu, Chen-Chi; Wang, Chien-Ying; Wen, Yi-Szu; Wu, Jackson Jer-Kan; Huang, Mu-Shun; Yang, Chen-Chang
Drug abuse is becoming more prevalent in Taiwan, as evidenced by increasing reports of drug trafficking and drug abuse-related criminal activity, and the wide use of more contemporary illicit drugs. Consequently, drug abuse-related accidents are also expected to occur with greater frequency. However, no study has yet specifically evaluated the prevalence, pattern, and outcomes of drug abuse-related accidents among patients visiting emergency departments (EDs) in Taiwan. We conducted an ambidirectional study with patients who visited the EDs of Taipei Veterans General Hospital (TVGH) and China Medical University Hospital (CMUH) due to drug abuse-related accidents from January 2007 through September 2009. Information on the patients' baseline characteristics and clinical outcomes was collected and analyzed. During the study period, a total of 166 patients visited the EDs of one of the two study hospitals due to drug abuse-related accidents. This yielded a prevalence of drug abuse of 0.1% among all patients visiting the ED due to accident and/or trauma. Fifty-six out of the 166 patients visited the ED at TVGH, most patients being between 21 and 40 years old. Opioids (41.1%) were the drugs most commonly abused by the patients, followed by benzodiazepines (32.1%). More than two-thirds of the patients (n=38, 67.9%) required hospitalization, and three patients died (5.4%). In contrast, 110 patients with drug abuse-related accidents visited the ED at CMUH during the study period. Most of these subjects had abused benzodiazepines (69.1%), were between 21 and 40 years old, and were female. Fewer than one-fifth of the patients (n=19, 17.3%) required hospitalization, with no deaths reported. There were significant between-hospital differences in terms of patient gender, drugs of choice, injury mechanisms, method and time of the ED visit, triage levels, and need for hospitalization. Although the prevalence of drug abuse-related accidents was low, and only three patient deaths
Rashidi, Mohammad-Reza; Soltani, Somaieh
Given the rising trend in medicinal chemistry strategy to reduce cytochrome P450-dependent metabolism, aldehyde oxidase (AOX) has recently gained increased attention in drug discovery programs and the number of drug candidates that are metabolized by AOX is steadily growing. Areas covered: Despite the emerging importance of AOX in drug discovery, there are certain major recognized problems associated with AOX-mediated metabolism of drugs. Intra- and inter-species variations in AOX activity, the lack of reliable and predictive animal models using the common experimental animals, and failure in the predictions of in vivo metabolic activity of AOX using traditional in vitro methods are among these issues that are covered in this article. A comprehensive review of computational human AOX (hAOX) related studies are also provided. Expert opinion: Following the recent progress in the stem cell field, the authors recommend the application of organoids technology as an effective tool to solve the fundamental problems associated with the evaluation of AOX in drug discovery. The recent success in resolving the hAOX crystal structure can too be another valuable data source for the study of AOX-catalyzed metabolism of new drug candidates, using computer-aided drug discovery methods.
Full Text Available The purpose of this study was to investigate the quality of a select group of medicines sold in accredited drug dispensing outlets (ADDOs and pharmacies in different regions of Tanzania as part of an in-depth cross-sectional assessment of community access to medicines and community use of medicines.We collected 242 samples of amoxicillin trihydrate, artemether-lumefantrine (ALu, co-trimoxazole, ergometrine maleate, paracetamol, and quinine from selected ADDOs and pharmacies in Mbeya, Morogoro, Singida, and Tanga regions. The analysis included physical examination and testing with validated analytical techniques. Assays for eight of nine products were conducted using high-performance thin-layer chromatography (HPTLC. For ALu tablets, we used a two-tiered approach, where tier 1 was a semi-quantitative Global Pharma Health Fund-Minilab® method and tier 2 was high-performance liquid chromatography (HPLC as described in The International Pharmacopoeia's monograph for artemether-lumefantrine.The physical examination of samples revealed no defects in the solid and oral liquid dosage forms, but unusual discoloration in an injectable solution, ergometrine maleate. For ALu, the results showed that of 38 samples, 31 (81.6% passed tier 1 testing and 7 (18.4% gave inconclusive drug content results. The inconclusive ALu samples were submitted for tier 2 testing and all met the quality standards. The pass rate using the HPTLC and TLC/HPLC assays was 93.8%; the failures were the ergometrine maleate samples purchased from both ADDOs and pharmacies. The disintegration testing of the solid dosage forms was conducted in accordance with US Pharmacopeia monographs. Only two samples of paracetamol, 1.2% of the solid dosage forms, failed to comply to standards. The study revealed a high overall rate of 92.6% of samples that met the quality standards. Although the overall failure rate was 7.4%, it is important to note that this was largely limited to one product and
Kaale, Eliangiringa; Manyanga, Vicky; Chambuso, Mhina; Liana, Jafary; Rutta, Edmund; Embrey, Martha; Layloff, Thomas; Johnson, Keith
The purpose of this study was to investigate the quality of a select group of medicines sold in accredited drug dispensing outlets (ADDOs) and pharmacies in different regions of Tanzania as part of an in-depth cross-sectional assessment of community access to medicines and community use of medicines. We collected 242 samples of amoxicillin trihydrate, artemether-lumefantrine (ALu), co-trimoxazole, ergometrine maleate, paracetamol, and quinine from selected ADDOs and pharmacies in Mbeya, Morogoro, Singida, and Tanga regions. The analysis included physical examination and testing with validated analytical techniques. Assays for eight of nine products were conducted using high-performance thin-layer chromatography (HPTLC). For ALu tablets, we used a two-tiered approach, where tier 1 was a semi-quantitative Global Pharma Health Fund-Minilab® method and tier 2 was high-performance liquid chromatography (HPLC) as described in The International Pharmacopoeia's monograph for artemether-lumefantrine. The physical examination of samples revealed no defects in the solid and oral liquid dosage forms, but unusual discoloration in an injectable solution, ergometrine maleate. For ALu, the results showed that of 38 samples, 31 (81.6%) passed tier 1 testing and 7 (18.4%) gave inconclusive drug content results. The inconclusive ALu samples were submitted for tier 2 testing and all met the quality standards. The pass rate using the HPTLC and TLC/HPLC assays was 93.8%; the failures were the ergometrine maleate samples purchased from both ADDOs and pharmacies. The disintegration testing of the solid dosage forms was conducted in accordance with US Pharmacopeia monographs. Only two samples of paracetamol, 1.2% of the solid dosage forms, failed to comply to standards. The study revealed a high overall rate of 92.6% of samples that met the quality standards. Although the overall failure rate was 7.4%, it is important to note that this was largely limited to one product and likely due to
Frederix, Geert W J; Hövels, Anke M; Severens, Johan L; Raaijmakers, Jan A M; Schellens, Jan H M
There is increasing discussion in the Netherlands about the introduction of a threshold value for the costs per extra year of life when reimbursing costs of new drugs. The Medicines Committee ('Commissie Geneesmiddelen'), a division of the Netherlands National Healthcare Institute ('Zorginstituut Nederland'), advises on reimbursement of costs of new drugs. This advice is based upon the determination of therapeutic value of the drug and the results of economic evaluations. Mathematical models that predict future costs and effectiveness are often used in economic evaluations; these models can vary greatly in transparency and quality due to author assumptions. Standardisation of cost-effectiveness models is one solution to overcome the unwanted variation in quality. Discussions about the introduction of a threshold value can only be meaningful if all involved are adequately informed, and by high quality in cost-effectiveness research and, particularly, economic evaluations. Collaboration and discussion between medical specialists, patients or patient organisations, health economists and policy makers, both in development of methods and in standardisation, are essential to improve the quality of decision making.
Champion, Katrina E; Teesson, Maree; Newton, Nicola C
The use of ecstasy is a public health problem and is associated with a range of social costs and harms. In recent years, there has been growing concern about the availability and misuse of new and emerging drugs designed to mimic the effects of illicit drugs, including ecstasy. This, coupled with the fact that the age of use and the risk factors for using ecstasy and emerging drugs are similar, provides a compelling argument to implement prevention for these substances simultaneously. The proposed study will evaluate whether a universal Internet-based prevention program, known as the Climate Schools: Ecstasy and Emerging Drugs Module, can address and prevent the use of ecstasy and emerging drugs among adolescents. A cluster randomised controlled trial will be conducted among Year 10 students (aged 15-16 years) from 12 secondary schools in Sydney, Australia. Schools will be randomly assigned to either the Climate Schools intervention group or the control group. All students will complete a self-report questionnaire at baseline, immediately post-intervention, and 6-, 12- and 24-months post-baseline. The primary outcome measures will include ecstasy and emerging drug-related knowledge, intentions to use these substances in the future, and the patterns of use of ecstasy and emerging drugs. A range of secondary outcomes will also be assessed, including beliefs and attitudes about ecstasy and emerging drugs, peer pressure resistance, other substance use and mental health outcomes. To our knowledge, this will be the first evaluation of an Internet-based program designed to specifically target ecstasy and NED use among adolescents. If deemed effective, the Climate Schools: Ecstasy and Emerging Drugs Module will provide schools with an interactive and novel prevention program for ecstasy and emerging drugs that can be readily implemented by teachers. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000708752.
Meehan, Timothy J; Bryant, Sean M; Aks, Steven E
The diagnosis and management of poisoned patients presenting with alterations in mental status can be challenging, as patients are often unable (or unwilling) to provide an adequate history. Several toxidromes exist. Recognition hinges upon vital signs and the physical examination. Understanding these "toxic syndromes" may guide early therapy and management, providing insight into the patient's underlying medical problem. Despite toxidrome recognition guiding antidotal therapy, the fundamental aspect of managing these patients involves meticulous supportive care. The authors begin with a discussion of various toxidromes and then delve into the drugs responsible for each syndrome. They conclude with a discussion on drug-facilitated sexual assault ("date rape"), which is both an underrecognized problem in the emergency department (ED) and representative of the drug-related problems faced in a modern ED. Copyright 2010. Published by Elsevier Inc.
Maggio, Antonella; Rosselli, Sergio; Bruno, Maurizio
The use of aromatic plants to relief different illness is not a new therapy. Actually aromatic plants have been used for many centuries by different cultures around the world. Pharmacological studies provide scientific support to the traditional use of aromatic medicinal plants and aromatherapy; nevertheless, more clinical trials are required regarding to their effectiveness in order to establish a guidance for their use in routine healthcare. Moreover, modern medicine in studies about olfactory function has attained great achievements and got Nobel Prize in 2004. These new searches have obviously fueled interest in the essential oils and volatile compounds of natural origin. Several reviews on the newly discovered AChEi obtained from plants, fungus and marine organisms have also been published over the last years. The majority of these AChEi belong to the alkaloid group, including indole, isoquinoline, quinolizidine, piperidine and steroidal alkaloids. Probably the interest in the essential oils and volatile compounds will be fueled from the new available scientific data about receptor on olfactory mucosa of nasal cavity. It can receive and distinguish different odor molecules, which produce nerve impulse and transmit into olfactory bulb via olfactory nerves. The nerve cells in the olfactory bulb transmit the signals into hippocampus. Because hippocampus is closely related with learning and memory functions, the volatile compounds can be potential drugs in AD therapies.
Augusto Afonso Guerra Jr
Full Text Available OBJETIVO: Avaliar a disponibilidade de medicamentos essenciais em localidades com índice de desenvolvimento humano OBJECTIVE: To investigate the availability of essential drugs in municipalities with a human development index < 0.699. METHODS: We surveyed 69 institutions, including municipal pharmacies, public clinics, private and philanthropic health units, and commercial pharmacies, in 19 municipalities of the state of Minas Gerais, Brazil. The municipalities were chosen according to the following selection criteria: (1 a human development index (HDI < 0.699 (the HDI for the entire state of Minas Gerais in 1991 in the microregion where the municipality was located; (2 the municipality had to be the seat of government for the microregion where it was located; (3 there had to be at least two eligible institutions (belonging to the public, private, or philanthropic sectors in full functioning in the municipality during the survey period. Health professionals who were directly responsible for stock control and drug dispensation at the institutions surveyed were interviewed. Institutional documents and records were also reviewed. A list of 21 tracer essential drugs, which were selected among the drugs most widely employed in the State of Minas Gerais’ Basic Pharmacy Program, was used to measure availability. The availability of each tracer drug was calculated at the time of the site visit and for the 12-month period immediately before the survey. In addition, the availability of tracer drugs was calculated for each type of institution surveyed. RESULTS: The availability of essential drugs in municipal pharmacies was 52.0%; in public health clinics, 46.9%; and in philanthropic and private health units, 41.0% and 38.1%, respectively. In commercial pharmacies, the availability of essential drugs reached 81.2%. CONCLUSION: The availability of essential drugs in public facilities is low and varies widely, with the result that persons who need such
Susan I Woodruff
Full Text Available Introduction: Visits to settings such as emergency departments (EDs may present a “teachable moment” in that a patient may be more open to feedback and suggestions regarding their risky alcohol and illicit drug-use behaviors. Screening, Brief Intervention, and Referral to Treatment (SBIRT is an ’opportunistic’ public health approach that targets low-risk users, in addition to those already dependent on alcohol and/or drugs. SBIRT programs provide patients with comprehensive screening and assessments, and deliver interventions of appropriate intensity to reduce risks related to alcohol and drug use. Methods: This study used a single group pre-post test design to assess the effect of the California SBIRT service program (i.e., CASBIRT on 6 substance-use outcomes (past-month prevalence and number of days of binge drinking, illegal drug use, and marijuana use. Trained bilingual/bicultural Health Educators attempted to screen all adult patients in 12 EDs/trauma centers (regardless of the reason for the patient’s visit using a short instrument, and then delivered a brief motivational intervention matched to the patient’s risk level. A total of 2,436 randomly selected patients who screened positive for alcohol and/or drug use consented to be in a 6-month telephone follow-up interview. Because of the high loss to follow-up rate, we used an intention-to-treat approach for the data analysis. Results: Results of generalized linear mixed models showed modest reductions in all 6 drug- and alcohol-use outcomes. Men (versus women, those at relatively higher risk status (versus lower risk, and those with only one substance of misuse (versus both alcohol and illicit drug misuse tended to show more positive change. Conclusion: These results suggest that SBIRT services provided in acute care settings are associated with modest changes in self-reported recent alcohol and illicit drug use. [West J Emerg Med. 2013;14(3:263–270.
Hoffman, Melissa B; Hill, Dane; Feldman, Steven R
Psoriasis is a common skin disorder associated with physical, social, psychological and financial burden. Over the past two decades, advances in our understanding of pathogenesis and increased appreciation for the multifaceted burden of psoriasis has led to new treatment development and better patient outcomes. Yet, surveys demonstrate that many psoriasis patients are either undertreated or are dissatisfied with treatment. There are many barriers that need be overcome to optimize patient outcomes and satisfaction. This review covers the current challenges associated with each major psoriasis treatment strategy (topical, phototherapy, oral medications and biologics). It also reviews the challenges associated with the psychosocial aspects of the disease and how they affect treatment outcomes. Patient adherence, inconvenience, high costs, and drug toxicities are all discussed. Then, we review the emerging drug delivery strategies in topical, oral, and biologic therapy. By outlining current treatment challenges and emerging drug delivery strategies, we hope to highlight the deficits in psoriasis treatment and strategies for how to overcome them. Regardless of disease severity, clinicians should use a patient-centered approach. In all cases, we need to balance patients' psychosocial needs, treatment costs, convenience, and effectiveness with patients' preferences in order to optimize treatment outcomes.
Mercolini, Laura; Protti, Michele
The term "new psychoactive substances" refers to emerging drugs of abuse whose chemical structure and psychoactive effects are similar to other already known compounds, often providing a "legal" alternative to internationally regulated drugs and mostly available via on-line retail sites. There are several categories of new psychoactive substances, such as synthetic cannabinoids, cathinone analogues, phenethylamines, tryptamines, and the need to identify and quantify an unprecedented and growing number of new compounds represents a unique challenge for toxicological and forensic analysis. The purpose of this review is to highlight biosampling, sample preparation and analysis of the most important classes of emerging drugs of abuse in biological matrices, focusing on alternatives to classical blood and urine "in tube" approach, still representing the standard routine for bioanalysis, despite inherent flaws regarding handling, stability and process feasibility. Chromatographic techniques coupled to mass spectrometry are usually exploited to identify and quantify new psychoactive substances; due to their high sensitivity and selectivity, it is possible to determine low concentrations not only in plasma and urine, but also in alternative matrices like dried blood spots, oral fluid, hair, other body fluids and tissues. Current literature on analytical methodologies applied to these samples is still limited and a more thorough validation is often required, including a comparison among the results obtained from conventional approaches and from innovative strategies, in order to determine their actual suitability. Copyright © 2016 Elsevier B.V. All rights reserved.
Full Text Available The opioid epidemic is the most significant modern-day, public health crisis. Physicians and lawmakers have developed methods and practices to curb opioid use. This article describes one method, prescription drug monitoring programs (PDMP, through the lens of how to optimize use for emergency departments (ED. EDs have rapidly become a central location to combat opioid abuse and drug diversion. PDMPs can provide emergency physicians with comprehensive prescribing information to improve clinical decisions around opioids. However, PDMPs vary tremendously in their accessibility and usability in the ED, which limits their effectiveness at the point of care. Problems are complicated by varying state-to-state requirements for data availability and accessibility. Several potential solutions to improving the utility of PDMPs in EDs include integrating PDMPs with electronic health records, implementing unsolicited reporting and prescription context, improving PDMP accessibility, data analytics, and expanding the scope of PDMPs. These improvements may help improve clinical decision-making for emergency physicians through better data, data presentation, and accessibility.
Described is a flow of authors' studies on the drug development in the title, aiming to save the life after the emergent exposure to peri-lethal dose. Medicals with radioprotective properties have been essentially those to be given before the exposure. Authors have studied the mechanism of bystander effect of non-exposed cells where they, localizing around the directly radiation-exposed cells, acquire the radioresistance; have found that nitrogen oxide (NO) is one of mediators for the effect; and have thought to apply the NO generating agents for the drug already clinically available, such as sodium nitroprusside (SNP), isosorbide nitrate (ISDN), nicolandil (NC), nitroglycerin (NG), and nipradilol (NP). ISDN, NC, NG and NP exhibited no in vitro-toxicity in colony formation of human fibroblast AG1522 cells up to 30 micro-M whereas SNP was toxic at the level >3 micro-M due to the formation of cyanide which could be detoxicated in vivo. Actually, the 5 agents were not toxic in vivo. When male jcl/ICR mice were irradiated with lethal dose of 7.5 Gy X-ray and the 5 agents were given to make their level 30 micro-M immediately, 1, 2 and 7 days after the exposure, 3/5 animals given SNP survived. With the half lethal dose of 6.5 Gy X-ray and 50 animals, SNP was further examined in details: survival was found to be 75-85% in mice given SNP in contrast to 30-40% in the control and the life-saving effect was suggested to be due to suppression of intestinal and marrow death with the improved feature of peripheral platelet and leukocyte. Thus SNP, a drug for angina pectoris, is found radioprotective even post exposure. (T.T.)
Bhattacharya, Sukanta S; Yadav, Jagjit S
Cytochrome P450 enzymes are a structurally conserved but functionally diverse group of heme-containing mixed function oxidases found across both prokaryotic and eukaryotic forms of the microbial world. Microbial P450s are known to perform diverse functions ranging from the synthesis of cell wall components to xenobiotic/drug metabolism to biodegradation of environmental chemicals. Conventionally, many microbial systems have been reported to mimic mammalian P450-like activation of drugs and were proposed as the in-vitro models of mammalian drug metabolism. Recent reports suggest that native or engineered forms of specific microbial P450s from these and other microbial systems could be employed for desired specific biotransformation reactions toward natural and synthetic (drug) compounds underscoring their emerging potential in drug improvement and discovery. On the other hand, microorganisms particularly fungi and actinomycetes have been shown to possess catabolic P450s with unusual potential to degrade toxic environmental chemicals including persistent organic pollutants (POPs). Wood-rotting basidiomycete fungi in particular have revealed the presence of exceptionally large P450 repertoire (P450ome) in their genomes, majority of which are however orphan (with no known function). Our pre- and post-genomic studies have led to functional characterization of several fungal P450s inducible in response to exposure to several environmental toxicants and demonstration of their potential in bioremediation of these chemicals. This review is an attempt to summarize the postgenomic unveiling of this versatile enzyme superfamily in microbial systems and investigation of their potential to synthesize new drugs and degrade persistent pollutants, among other biotechnological applications. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Palmer, Alan M
Multiple sclerosis (MS) is a neurodegenerative disease with a major inflammatory component that constitutes the most common progressive and disabling neurological condition in young adults. Injectable immunomodulatory medicines such as interferon drugs and glatiramer acetate have dominated the MS market for over the past two decades but this situation is set to change. This is because of: (i) patent expirations, (ii) the introduction of natalizumab, which targets the interaction between leukocytes and the blood-CNS barrier, (iii) the launch of three oral immunomodulatory drugs (fingolimod, dimethyl fumarate and teriflunomide), with another (laquinimod) under regulatory review and (iv) a number of immunomodulatory monoclonal antibodies (alemtuzumab, daclizumab and ocrelizumab) about to enter the market. Current and emerging medicines are reviewed and their impact on people with MS considered. © 2013 The British Pharmacological Society.
Zhang, Yi; Long, Mei; Huang, Peng; Yang, Huaming; Chang, Shi; Hu, Yuehua; Tang, Aidong; Mao, Linfeng
Nanoclay can be incorporated into emerging dual functional drug delivery systems (DDSs) to promote efficiency in drug delivery and reduce the toxicity of doxorubicin (DOX) used for thyroid cancer treatment. This paper reports the expansion of the basal spacing of kaolinite nanoclay was expanded from 0.72 nm to 0.85 nm, which could provide sufficiently spacious site for hosting doxorubicin molecules and controlling the diffusion rate. A targeted design for papillary thyroid cancer cells was achieved by introducing KI, which is consumed by the sodium-iodide symporter (NIS). As indicated by MTT assays, confocal laser scanning microscopy and bio-TEM observations, methoxy-intercalated kaolinite (KaolinMeOH) exhibited negligible cytotoxicity against papillary thyroid cancer cells. By contrast, DOX-KaolinMeOH showed dose-dependent therapeutic effects in vitro, and KI@DOX-KaolinMeOH was found to act as a powerful targeted therapeutic drug. Furthermore, active and passive targeting strategies played a role in the accumulation of the drug molecules, as verified by an in vivo bio-distribution analysis.
Diep, Jack; Chin, David Tian; Gupta, Somdatta; Syed, Faraz; Xiong, Ming; Cheng, Jianguo
Kratom is an herb indigenous to Southeast Asia with psychoactive opioid compounds, often used as a treatment for chronic pain or opiate withdrawal symptoms. It is legally and readily available via Internet sales and has been identified as an emerging drug of abuse in the United States. Kratom use has been associated with psychosis, seizures, and even death. At lower doses, kratom acts as a stimulant, while at higher doses, it produces analgesia and euphoria. Here, we describe the successful management of kratom overdose and withdrawal in a young man with negative toxicology screens.
Palepu, A; Strathdee, S A; Hogg, R S; Anis, A H; Rae, S; Cornelisse, P G; Patrick, D M; O'Shaughnessy, M V; Schechter, M T
The aim of this study was to describe the relationship between sociodemographic characteristics and human immunodeficiency (HIV) status of a cohort of injection drug users (IDUs) on their self-reported health service utilization. Interviewer-administered questionnaire. IDUs who had injected illicit drugs within the previous month were recruited through street outreach. They underwent serology for HIV-1 and questionnaires on demographics, drug using behaviors, housing status, and health service utilization (hospitalization overnight and emergency department visits) in the previous 6 months. Logistic regression analysis was used to identify independent associations with the use of health services. Of 1,103 cohort participants, 65% were male, 63% were white, and 23% were HIV positive. Cocaine was the most frequently injected drug used. Almost half (47%) had used health services in the previous 6 months. The following variables were associated independently with health service utilization (adjusted odds ratio; 95% confidence interval): unstable housing, defined as living primarily in a hotel, boarding room, or transition house or on the street in the past 6 months (1.44; 1.11-1.86); female gender (1.45; 1.11-1.89); HIV-positive status (1.43; 1.06-1.92); injection of cocaine (1.50; 1.12-2.02); and primary care I physician visit in past 6 months (1.91; 1.39-2.64). IDUs with unstable housing were more likely to report emergency department and hospital use, which may be a reflection of their disorganized lifestyle or poorer health status. Further studies are required to assess the effect on the health status and health care use of IDUs of interventions that increase the availability of safe, affordable housing.
Duarte, Antonia Eliene; de Menezes, Irwin Rose Alencar; Bezerra Morais Braga, Maria Flaviana; Leite, Nadghia Figueiredo; Barros, Luiz Marivando; Waczuk, Emily Pansera; Pessoa da Silva, Maria Arlene; Boligon, Aline; Teixeira Rocha, João Batista; Souza, Diogo Onofre; Kamdem, Jean Paul; Melo Coutinho, Henrique Douglas; Escobar Burger, Marilise
Rhaphiodon echinus is a weed plant used in the Brazilian folk medicinal for the treatment of infectious diseases. In this study, the essential oil of R. echinus leaf was investigated for its antimicrobial properties. The chemical constituents of the essential oil were characterized by GC-MS. The antimicrobial properties were determined by studying by the microdilution method the effect of the oil alone, and in combination with antifungal or antibiotic drugs against the fungi Candida albicans, Candida krusei and Candida tropicalis and the microbes Escherichia coli, Staphylococcus aureus and Pseudomonas. In addition, the iron (II) chelation potential of the oil was determined. The results showed the presence of β-caryophyllene and bicyclogermacrene in major compounds, and revealed a low antifungal and antibacterial activity of the essential oil, but a strong modulatory effect on antimicrobial drugs when associated with the oil. The essential oil showed iron (II) chelation activity. The GC-MS characterization revealed the presence of monoterpenes and sesquiterpenes in the essential oil and metal chelation potential, which may be responsible in part for the modulatory effect of the oil. These findings suggest that essential oil of R. echinus is a natural product capable of enhancing the antibacterial and antifungal activity of antimicrobial drugs.
Simpson, Sean S; Adams, Nikki; Brugman, Claudia M; Conners, Thomas J
With the rapid development of new psychoactive substances (NPS) and changes in the use of more traditional drugs, it is increasingly difficult for researchers and public health practitioners to keep up with emerging drugs and drug terms. Substance use surveys and diagnostic tools need to be able to ask about substances using the terms that drug users themselves are likely to be using. Analyses of social media may offer new ways for researchers to uncover and track changes in drug terms in near real time. This study describes the initial results from an innovative collaboration between substance use epidemiologists and linguistic scientists employing techniques from the field of natural language processing to examine drug-related terms in a sample of tweets from the United States. The objective of this study was to assess the feasibility of using distributed word-vector embeddings trained on social media data to uncover previously unknown (to researchers) drug terms. In this pilot study, we trained a continuous bag of words (CBOW) model of distributed word-vector embeddings on a Twitter dataset collected during July 2016 (roughly 884.2 million tokens). We queried the trained word embeddings for terms with high cosine similarity (a proxy for semantic relatedness) to well-known slang terms for marijuana to produce a list of candidate terms likely to function as slang terms for this substance. This candidate list was then compared with an expert-generated list of marijuana terms to assess the accuracy and efficacy of using word-vector embeddings to search for novel drug terminology. The method described here produced a list of 200 candidate terms for the target substance (marijuana). Of these 200 candidates, 115 were determined to in fact relate to marijuana (65 terms for the substance itself, 50 terms related to paraphernalia). This included 30 terms which were used to refer to the target substance in the corpus yet did not appear on the expert-generated list and were
Burke, Thomas F; Suarez, Sebastian; Sessler, Daniel I; Senay, Ayla; Yusufali, Taha; Masaki, Charles; Guha, Moytrayee; Rogo, Debora; Jani, Pankaj; Nelson, Brett D; Rogo, Khama
Lack of access to emergency and essential surgery is widespread in low- and middle-income countries. Scarce anesthesia services contribute to this unmet need. The aim of this study was to evaluate the safety and feasibility of the Every Second Matters for Emergency and Essential Surgery-Ketamine (ESM-Ketamine) package for emergency and essential procedures when no anesthetist was available. From November 2013 to September 2017, the ESM-Ketamine package was used for patients requiring emergency or life-improving surgeries in fifteen selected facilities across Kenya when no anesthetist was available. A mixed-methods approach was used to assess safety and feasibility of the ESM-Ketamine package, including demand, acceptability, and practicality. The primary outcome was ketamine-related adverse events. Key-informant interviews captured perceptions of providers, hospital administrators, and surgeons/proceduralists. Non-anesthetist mid-level providers used ESM-Ketamine for 1216 surgical procedures across the fifteen study facilities. The median ketamine dose was 2.1 mg/kg. Brief (30 s) oxygen desaturations occurred in seven patients (0.6%). There were 157 (13%) reported cases of hallucinations and agitation which were treated with diazepam. All patients recovered uneventfully, and no ketamine-related deaths were reported. Twenty-seven key-informant interviews showed strong support for the program with four main themes: financial considerations, provision of services, staff impact, and scaling considerations. The ESM-Ketamine package appears safe and feasible and is capable of expanding access to emergency and essential surgeries in rural Kenya when no anesthetist is available.
An emerging trend in the biotechnology industry is the utilization of plastic components in manufacturing systems for the production of an active pharmaceutical ingredient (API) or a finished drug product (FDP). If the API, the FDP, or any solution used to generate them (for example, process streams such as media, buffers, and the like) come in contact with a plastic at any time during the manufacturing process, there is the potential that substances leached from the plastic may accumulate in the API or FDP, affecting safety and/or efficacy. In this article the author develops a terminology that addresses process streams associated with the manufacturing process. Additionally, the article outlines the safety assessment process for manufacturing systems, specifically addressing the topics of risk management and the role of compendial testing. Finally, the proper use of vendor-supplied extractables information is considered. Manufacturing suites used to produce biopharmaceuticals can include components that are made out of plastics. Thus it is possible that substances could leach out of the plastics and into manufacturing solutions, and it is further possible that such leachables could accumulate in the pharmaceutical product. In this article, the author develops a terminology that addresses process streams associated with the manufacturing process. Additionally, the author proposes a process by which the impact on product safety of such leached substances can be assessed.
Grund, Jean-Paul C; Latypov, Alisher; Harris, Magdalena
Krokodil, a homemade injectable opioid, gained its moniker from the excessive harms associated with its use, such as ulcerations, amputations and discolored scale-like skin. While a relatively new phenomenon, krokodil use is prevalent in Russia and the Ukraine, with at least 100,000 and around 20,000 people respectively estimated to have injected the drug in 2011. In this paper we review the existing information on the production and use of krokodil, within the context of the region's recent social history. We searched PubMed, Google Advanced Search, Google Scholar, YouTube and the media search engine www.Mool.com for peer reviewed or media reports, grey literature and video reports. Survey data from HIV prevention and treatment NGOs was consulted, as well as regional experts and NGO representatives. Krokodil production emerged in an atypical homemade drug production and injecting risk environment that predates the fall of communism. Made from codeine, the active ingredient is reportedly desomorphine, but - given the rudimentary 'laboratory' conditions - the solution injected may include various opioid alkaloids as well as high concentrations of processing chemicals, responsible for the localized and systemic injuries reported here. Links between health care and law enforcement, stigma and maltreatment by medical providers are likely to thwart users seeking timely medical help. A comprehensive response to the emergence of krokodil and associated harms should focus both on the substance itself and its rudimentary production methods, as well as on its micro and macro risk environments - that of the on-going syndemic of drug injecting, HIV, HCV, TB and STIs in the region and the recent upheaval in local and international heroin supply. The feasibility of harm reduction strategies for people who inject krokodil may depend more on political will than on the practical implementation of interventions. The legal status of opioid substitution treatment in Russia is a point
West, Sophie; Bhugra, Praveen
Aims Currently, treatment for Alzheimer’s disease (AD) focuses on the cholinergic hypothesis and provides limited symptomatic effects. Research currently focuses on other factors that are thought to contribute to AD development such as tau proteins and Aβ deposits, and how modification of the associated pathology affects outcomes in patients. This systematic review summarizes and appraises the evidence for the emerging drugs affecting Aβ and tau pathology in AD. Methods A comprehensive, systematic online database search was conducted using the databases ScienceDirect and PubMed to include original research articles. A systematic review was conducted following a minimum set of standards, as outlined by The PRISMA Group 1. Specific inclusion and exclusion criteria were followed and studies fitting the criteria were selected. No human trials were included in this review. In vitro and in vivo AD models were used to assess efficacy to ensure studied agents were emerging targets without large bodies of evidence. Results The majority of studies showed statistically significant improvement (P < 0.05) of Aβ and/or tau pathology, or cognitive effects. Many studies conducted in AD animal models have shown a reduction in Aβ peptide burden and a reduction in tau phosphorylation post-intervention. This has the potential to reduce plaque formation and neuronal degeneration. Conclusions There are many emerging targets showing promising results in the effort to modify the pathological effects associated with AD. Many of the trials also provided evidence of the clinical effects of such drugs reducing pathological outcomes, which was often demonstrated as an improvement of cognition. PMID:25753046
Jiang, Yanjiao; Chen, Jing; Deng, Chao; Suuronen, Erik J; Zhong, Zhiyuan
Hydrogels, microgels and nanogels have emerged as versatile and viable platforms for sustained protein release, targeted drug delivery, and tissue engineering due to excellent biocompatibility, a microporous structure with tunable porosity and pore size, and dimensions spanning from human organs, cells to viruses. In the past decade, remarkable advances in hydrogels, microgels and nanogels have been achieved with click chemistry. It is a most promising strategy to prepare gels with varying dimensions owing to its high reactivity, superb selectivity, and mild reaction conditions. In particular, the recent development of copper-free click chemistry such as strain-promoted azide-alkyne cycloaddition, radical mediated thiol-ene chemistry, Diels-Alder reaction, tetrazole-alkene photo-click chemistry, and oxime reaction renders it possible to form hydrogels, microgels and nanogels without the use of potentially toxic catalysts or immunogenic enzymes that are commonly required. Notably, unlike other chemical approaches, click chemistry owing to its unique bioorthogonal feature does not interfere with encapsulated bioactives such as living cells, proteins and drugs and furthermore allows versatile preparation of micropatterned biomimetic hydrogels, functional microgels and nanogels. In this review, recent exciting developments in click hydrogels, microgels and nanogels, as well as their biomedical applications such as controlled protein and drug release, tissue engineering, and regenerative medicine are presented and discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.
Nirmalanandhan, Victor Sanjit; Sittampalam, G Sitta
Stem cells, irrespective of their origin, have emerged as valuable reagents or tools in human health in the past 2 decades. Initially, a research tool to study fundamental aspects of developmental biology is now the central focus of generating transgenic animals, drug discovery, and regenerative medicine to address degenerative diseases of multiple organ systems. This is because stem cells are pluripotent or multipotent cells that can recapitulate developmental paths to repair damaged tissues. However, it is becoming clear that stem cell therapy alone may not be adequate to reverse tissue and organ damage in degenerative diseases. Existing small-molecule drugs and biologicals may be needed as "molecular adjuvants" or enhancers of stem cells administered in therapy or adult stem cells in the diseased tissues. Hence, a combination of stem cell-based, high-throughput screening and 3D tissue engineering approaches is necessary to advance the next wave of tools in preclinical drug discovery. In this review, the authors have attempted to provide a basic account of various stem cells types, as well as their biology and signaling, in the context of research in regenerative medicine. An attempt is made to link stem cells as reagents, pharmacology, and tissue engineering as converging fields of research for the next decade.
Yosef H Al-Olah; Khalifa M Al Thiab
Hospital admissions due to drug-related problems (DRPs) have been studied internationally, but local data are limited. Therefore, we undertook a prospective, observational study of all admissions through the emergency department (ED) at a tertiary referral hospital in Saudi Arabia to determine the incidence of admissions through the ED due to DRPs, types of DRPs, length of stay (LOS) in the hospital after ED admissions due to DRPs, and assessment of preventability of admissions due to DRPs.All admissions through the ED over a period of 28 consecutive days were evaluated to determine if they were due to definite or possible DRPs. Data was collected on a daily basis for each admission over the previous 24 hours. Each incident was assessed by three investigators Of 557 patients admitted through the ED, 82 (14.7%) admissions were due to DRP (53 definite, 29 possible). The most common types of DRP were failure to receive medication in 25 cases (47.2%), an adverse drug reaction in 13 cases (24.5%), and drug overdose in 6 cases (11.3%). In the definite DRP group, 83.0% were definitely preventable, 3.8% were possibly preventable and 13.2% were definitely non-preventable.DRPs are a serious and costly issue facing health care professionals and health care systems. Most admissions due to DRPs are avoidable (Author).
Sarkar, Narendra Nath
Full Text Available The objective of this study is to evaluate and elucidated the potential of selective progesterone receptor modulators (SPRMs to be an effective emergency contraception (EC. The data are extracted from the literature through the MEDLINE database service from 2000–2010. The SPRMs are in fact progesterone receptor ligands that could bind to progesterone receptor (PR and exert antagonistic, agonistic or mixed agonist-antagonistic effects. These SPRMs are mifepristone, onapristone, asoprisnil, ulipristal, proellex among other compounds. Currently developed SPRMs may exert contraceptive effects by inhibiting ovulation and retarding endometrial synchronization. Low-doses of progesterone antagonists retard endometrial maturation without affecting ovulation. Mifepristone being a SPRM is effective for prevention of pregnancy but with prostaglandin acts as an excellent abortifacient; yet could not compete with levonorgestrel as EC. However, a single dose of 30 mg ulipristal acetate, another SPRM with similar effectiveness and side effect profiles as 1.5 mg levonorgestrel EC, has shown wider ‘window of effect’ by inhibition of the LH peak even if administered at the advanced pre-ovulatory phase, a time when use of levonorgestrel EC is no longer effective. Thus, ulipristal acetate goes one-step ahead of levonorgestrel in the field of emergency contraception treatment. Further studies are needed to explore the potential of other SPRMs to be cutting edge emergency contraceptive drugs.
Hu, Xingdi; Primack, Brian A; Barnett, Tracey E; Cook, Robert L
K2 or "spice" has emerged as a popular legal alternative to marijuana among adolescents and young adults. However, no data has been published assessing prevalence of and associations with ever K2 use in any population. This study's aims were to examine prevalence of ever K2 use among a sample of college students, to determine characteristics of persons who use K2, and to access the association between K2 and other drug use. Ever use of K2 was reported by 69 (8%) of the sample of 852 college students. Response rate was 36%. Bivariate and multivariate analyses assessed whether sociodemographic characteristics and other drug use were associated with ever use of K2. Ever use of K2 was reported by 69 (8%) of the sample. Among these 69 individuals, 61 (88%) had used a cigarette and 25 (36%) had used a hookah to smoke K2. In multivariate analyses, K2 use was more common in males (vs. females, adjusted Odds Ratio (aOR)=2.0, 95% Confidence Interval (CI)=1.2-3.5, p=0.01) and 1st or 2nd year college students (vs. 3rd year or above, aOR=2.4, 95% CI=1.2-5.0, p=0.02). Ever use of K2 in this sample was higher than ever use of many other drugs of abuse that are commonly monitored in adolescents and young adults. Although DEA had banned five synthetic cannabinoids recently, clinicians and public health officials concerned with substance abuse in youth should be aware of and monitor the use of this drug in college students over time. © 2011 Hu et al; licensee BioMed Central Ltd.
Barnett Tracey E
Full Text Available Abstract Background K2 or "spice" has emerged as a popular legal alternative to marijuana among adolescents and young adults. However, no data has been published assessing prevalence of and associations with ever K2 use in any population. This study's aims were to examine prevalence of ever K2 use among a sample of college students, to determine characteristics of persons who use K2, and to access the association between K2 and other drug use. Findings Ever use of K2 was reported by 69 (8% of the sample of 852 college students. Response rate was 36%. Bivariate and multivariate analyses assessed whether sociodemographic characteristics and other drug use were associated with ever use of K2. Ever use of K2 was reported by 69 (8% of the sample. Among these 69 individuals, 61 (88% had used a cigarette and 25 (36% had used a hookah to smoke K2. In multivariate analyses, K2 use was more common in males (vs. females, adjusted Odds Ratio (aOR = 2.0, 95% Confidence Interval (CI = 1.2-3.5, p = 0.01 and 1st or 2nd year college students (vs. 3rd year or above, aOR = 2.4, 95% CI = 1.2-5.0, p = 0.02. Conclusions Ever use of K2 in this sample was higher than ever use of many other drugs of abuse that are commonly monitored in adolescents and young adults. Although DEA had banned five synthetic cannabinoids recently, clinicians and public health officials concerned with substance abuse in youth should be aware of and monitor the use of this drug in college students over time.
Boonyanugomol, Wongwarut; Kraisriwattana, Kairin; Rukseree, Kamolchanok; Boonsam, Kraisorn; Narachai, Panchaporn
In this study, we determined the antibacterial and synergistic activities of the essential oil from Zingiber cassumunar against the extensively drug-resistant (XDR) Acinetobacter baumannii strains. The antibacterial and synergistic properties of the essential oil from Z. cassumunar were examined by agar disc diffusion tests. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated by broth microdilution using the resazurin assay. The in vitro time-kill antibacterial kinetics was analyzed using the plate count technique. We found that the essential oil from Z. cassumunar had antibacterial activity against A. baumannii, with MIC and MBC ranging from 7.00 to 9.24mg/ml. The essential oil could completely inhibit A. baumannii at 1h, and coccoid-shaped bacteria were found after treatment. In addition, the essential oil had a synergistic effect when combined with antibiotics, e.g., aminoglycosides, fluoroquinolones, tetracyclines, and folate pathway inhibitors. Thus, the essential oil from Z. cassumunar has strong antibacterial and synergistic activities against XDR A. baumannii, which may provide the basis for the development of a new therapy against drug-resistant bacteria. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Unemo, Magnus; Nicholas, Robert A
The new superbug Neisseria gonorrhoeae has retained resistance to antimicrobials previously recommended for first-line treatment and has now demonstrated its capacity to develop resistance to the extended-spectrum cephalosporin, ceftriaxone, the last remaining option for first-line empiric treatment of gonorrhea. An era of untreatable gonorrhea may be approaching, which represents an exceedingly serious public health problem. Herein, we review the evolution, origin and spread of antimicrobial resistance and resistance determinants (with a focus on extended-spectrum cephalosporins) in N. gonorrhoeae, detail the current situation regarding verified treatment failures with extended-spectrum cephalosporins and future treatment options, and highlight essential actions to meet the large public health challenge that arises with the possible emergence of untreatable gonorrhea. Essential actions include: implementing action/response plans globally and nationally; enhancing surveillance of gonococcal antimicrobial resistance, treatment failures and antimicrobial use/misuse; and improving prevention, early diagnosis and treatment of gonorrhea. Novel treatment strategies, antimicrobials (or other compounds) and, ideally, a vaccine must be developed. PMID:23231489
Edwards, Sarah J L
Clinical research under the usual regulatory constraints may be difficult or even impossible in a public health emergency. Regulators must seek to strike a good balance in granting as wide therapeutic access to new drugs as possible at the same time as gathering sound evidence of safety and effectiveness. To inform current policy, I reexamine the philosophical rationale for restricting new medicines to clinical trials, at any stage and for any population of patients (which resides in the precautionary principle), to show that its objective to protect public health, now or in the future, could soon be defeated in a pandemic. Providing wider therapeutic access and coordinating observations and natural experiments, including service delivery by cluster (wedged cluster trials), may provide such a balance. However, there are important questions of fairness to resolve before any such research can proceed.
Full Text Available Nigella sativa has attracted healers in ancient civilizations and researchers in recent times. Traditionally, it has been used in different forms to treat many diseases including asthma, hypertension, diabetes, inflammation, cough, bronchitis, headache, eczema, fever, dizziness and influenza. Experimentally, it has been demonstrated that N. sativa extracts and the main constituent of their volatile oil, thymoquinone, possess antioxidant, anti-inflammatory and hepatoprotective properties. In this review we aimed at summarizing the most recent investigations related to a few and most important effects of thymoquinone. It is concluded that thymoquinone has evidently proved its activity as hepatoprotective, anti-inflammatory, antioxidant, cytotoxic and anti-cancer chemical, with specific mechanisms of action, which provide support to consider this compound as an emerging drug. Further research is required to make thymoquinone a pharmaceutical preparation ready for clinical trials.
Wood, Matthew R; Lalancette, Roger A; Bernal, Ivan
The name `bath salts', for an emerging class of synthetic cathinones, is derived from an attempt to evade prosecution and law enforcement. These are truly illicit drugs that have psychoactive CNS (central nervous system) stimulant effects and they have seen a rise in abuse as recreational drugs in the last few years since first having been seen in Japan in 2006. The ease of synthesis and modification of specific functional groups of the parent cathinone make these drugs particularly difficult to regulate. MDPV (3,4-methylenedioxypyrovalerone) is commonly encountered as its hydrochloride salt (C16H21NO3·HCl), in either the hydrated or the anhydrous forms. This `bath salt' has various names in the US, e.g. `Super Coke', `Cloud Nine', and `Ivory Wave', to name just a few. We report here the structures of two forms of the HCl salt, one as a mixed bromide/chloride salt, C16H22NO3(+)·0.343Br(-)·0.657Cl(-) [systematic name: 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one bromide/chloride (0.343/0.657)], and the other with the H7O3(+) cation, as well as the HCl counter-ion [systematic name: hydroxonium 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one dichloride, H7O3(+)·C16H22NO3(+)·2Cl(-)]. This is one of a very few structures (11 to be exact) in which we have a new example of a precisely determined hydroxonium cation. During the course of researching the clandestine manufacture of MDPV, we were surprised by the fact that a common precursor of this illicit stimulant is known to be the fragrant species piperonal, which is present in the fragrances of orchids, most particularly in the case of the vanilla orchid. We found that MDPV can be made by a Grignard reaction of this heliotropin. This may also explain the unexpected appearance of the bromide counter-ion in some of the salts we encountered (C16H21NO3·HBr), one of which is presented here [systematic name: 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one
Correia-da-Silva, Marta; Sousa, Emília; Pinto, Madalena M M
Nature uses sulfation of endogenous and exogenous molecules mainly to avoid potential toxicity. The growing importance of natural sulfated molecules, as modulators of a number of physiological and pathological processes, has inspired the synthesis of non-natural sulfated scaffolds. Until the 1990s, the synthesis of sulfated small molecules was almost restricted to derivatives of flavonoids and aimed mainly at structure elucidation and plant biosynthesis studies. Currently, the synthesis of this type of compounds concerns structurally diverse scaffolds and is aimed at the development of potential drugs and/or exploitation of the biological effects of sulfated metabolites. Some important hit compounds are emerging from sulfated flavonoids and other polyphenols mainly as anticoagulant and antiviral agents. When compared with polymeric macromolecules such as heparins, sulfated small molecules could be of value in therapeutics due to their hydrophobic nature that can contribute to improve the bioavailability. This review highlights the synthetic approaches that were applied to obtain monosulfated or polysulfated phenolic small molecules and compiles the diverse biological activities already reported for this type of derivatives. Toxicity and pharmacokinetic parameters of this emerging class of derivatives will also be considered, emphasizing their value for therapeutic applications. © 2013 Wiley Periodicals, Inc.
Pereira, Tiago Campos; Lopes-Cendes, Iscia
An emerging new category of therapeutic agents based on ribonucleic acid has emerged and shown very promising in vitro, animal and pre-clinical results, known as small interfering RNAs (siRNAs), microRNAs mimics (miRNA mimics) and their derivates. siRNAs are small RNA molecules that promote potent and specific silencing of mutant, exogenous or aberrant genes through a mechanism known as RNA interference. These agents have called special attention to medicine since they have been used to experimentally treat a series of neurological conditions with distinct etiologies such as prion, viral, bacterial, fungal, genetic disorders and others. siRNAs have also been tested in other scenarios such as: control of anxiety, alcohol consumption, drug-receptor blockage and inhibition of pain signaling. Although in a much earlier stage, miRNAs mimics, anti-miRs and small activating RNAs (saRNAs) also promise novel therapeutic approaches to control gene expression. In this review we intend to introduce clinicians and medical researchers to the most recent advances in the world of siRNA- and miRNA-mediated gene control, its history, applications in cells, animals and humans, delivery methods (an yet unsolved hurdle), current status and possible applications in future clinical practice.
Knezevic, Petar; Aleksic, Verica; Simin, Natasa; Svircev, Emilija; Petrovic, Aleksandra; Mimica-Dukic, Neda
Traditional herbal medicine has become an important issue on the global scale during the past decade. Among drugs of natural origin, special place belongs to essential oils, known as strong antimicrobial agents that can be used to combat antibiotic-resistant bacteria. Eucalyptus camaldulensis leaves are traditional herbal remedy used for various purposes, including treatment of infections. The aim of this study was to determine antimicrobial potential of two E. camaldulensis essential oils against multi-drug resistant (MDR) Acinetobacter baumannii wound isolates and to examine possible interactions of essential oils with conventional antimicrobial agents. Chemical composition of essential oils was determined by gas chromatography-mass spectrometry analysis (GC-MS). MIC values of essential oils against A. baumannii strains were estimated by modified broth microdilution method. The components responsible for antimicrobial activity were detected by bioautographic analysis. The potential synergy between the essential oils and antibiotics (ciprofloxacin, gentamicin and polymyxin B) was examined by checkerboard method and time kill curve. The dominant components of both essential oils were spatulenol, cryptone, p-cimene, 1,8-cineole, terpinen-4-ol and β-pinene. The detected MICs for the E. camaldulensis essential oils were in range from 0.5 to 2 μl mL(-1). The bioautographic assay confirmed antibacterial activity of polar terpene compounds. In combination with conventional antibiotics (ciprofloxacin, gentamicin and polymyxin B), the examined essential oils showed synergistic antibacterial effect in most of the cases, while in some even re-sensitized MDR A. baumannii strains. The synergistic interaction was confirmed by time-kill curves for E. camaldulensis essential oil and polymyxin B combination which reduced bacterial count under detection limit very fast, i.e. after 6h of incubation. The detected anti-A. baumannii activity of E. camaldulensis essential oils
Liakoni, Evangelia; Dolder, Patrick C.; Rentsch, Katharina; Liechti, Matthias E.
QUESTIONS UNDER STUDY: To describe acute toxicity of recreational drugs including novel psychoactive substances. METHODS: We included all cases presenting at the emergency department (ED) of the University Hospital of Basel, Switzerland, between October 2013 and September 2014 with acute toxicity due to self-reported recreational drug use or with symptoms/signs consistent with acute toxicity. Isolated ethanol intoxications were excluded. Intoxications were confirmed with immunoassa...
Soekmadji, Carolina; Nelson, Colleen C
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.
Thent, Zar Chi; Das, Srijit; Zaidun, Nurul Hannim
The incidence of diabetes mellitus has increased drastically over the past few decades. This oxidant-antioxidant imbalance resulting in complication of diabetes mellitus includes macro- and microvascular complications. Resistance to conventional treatment and patient compliance has paved the way to the usage of effective natural products and supplements. Momordica charantia (bitter gourd) is widely consumed in many parts of Malaysia as a vegetable. Momordica charantia (MC) is mainly used in the management of diabetes mellitus. The present review discusses the literature concerning the antidiabetic and antioxidant properties of MC focusing on the complication of diabetes mellitus along with its mode of delivery. We found that among the whole part of MC, its fruit extract has been widely studied, therapeutically. The evidence based analysis of the beneficiary effects of MC on the different organs involved in diabetes complication is also highlighted. This review elucidated an essential understanding of MC based drug delivery system in both clinical and experimental studies and appraised the great potential of the protein based MC extract against diabetes mellitus. The review paper is believed to assist the researchers and medical personnel in treating diabetic associated complications. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Mastour S Alghamdy
Full Text Available Background and Aim: Medication Errors can result in drug-related problems (DRPs. Insight into the frequency, type, and severity of DRPs could help reduce their incidence. The aim of the present study was to estimate the prevalence of admissions as a result of DRPs at the Emergency Department (ED of a university hospital in the Kingdom of Saudi Arabia. Materials and Methods: Files of suspected cases of DRPs reporting to ED in the year 2012 were scrutinized. Suspicion arose from the hospital record system based on Diagnosis Code Numbers (ICD-9-CM, Professional 2010 and from triggers, such as some drugs, laboratory tests, and signs and symptoms pointing to DRPs. Results: Of 5574 admissions, 253 (4.5% were DRPs and were categorized as: Overdose toxicity and side effects of drugs 50 (19.8%, drug-interactions 29 (11.5%, accidental and suicidal drug ingestions 26 (10.3%, drug abuse 18 (7.1%, drug allergy 10 (4%, super-infections 8 (3.2%, and noncompliance to treatment 112 (44.3%. About 70% of DRPs were preventable; 67 (26.5% required hospital admission for 7-102 days and 10 (4% died. Conclusions: Noncompliance to treatment, overdose toxicity, drug interactions, and drug abuse are important causes of hospital admissions as a result of DRPs. Awareness of prescribers to the problem and their education would help to prevent them and improve patient care.
Comiskey, Catherine Maria; O'Sullivan, Karin; Milnes, Jennie
The objective was to assess need, evaluate projects, and devise a roadmap for future provision given budget cuts. The analysis of 30 substance misuse services in towns and rural areas of Ireland was conducted in 2010. Analysis revealed that 24,315 (95% CI 12,928-40,629) individuals were using illegal drugs in 2006, 893 individuals were using opiates, opiate and cocaine use was increasing as was drug use amongst females. Evaluations demonstrated that not all services were meeting emerging needs, services lacked administrative support, and funding needed to be redirected. The RAR approach was useful for policy decisions and budget cuts in times of economic restraint.
Soller, Brian; Lee, Juliet P.
This article examines why Southeast Asian American adolescents and emerging adults in two urban settings prefer to use "blunts," or hollowed-out cigars filled with marijuana, over other methods of drug intake. Rationales for preferring blunts were both instrumental and social. Blunts allowed users to more easily share marijuana, the preferred drug…
Lai, Foon Yin; Thai, Phong K; O'Brien, Jake; Gartner, Coral; Bruno, Raimondo; Kele, Benjamin; Ort, Christoph; Prichard, Jeremy; Kirkbride, Paul; Hall, Wayne; Carter, Steve; Mueller, Jochen F
Wastewater analysis provides a non-intrusive way of measuring drug use within a population. We used this approach to determine daily use of conventional illicit drugs [cannabis, cocaine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA)] and emerging illicit psychostimulants (benzylpiperazine, mephedrone and methylone) in two consecutive years (2010 and 2011) at an annual music festival. Daily composite wastewater samples, representative of the festival, were collected from the on-site wastewater treatment plant and analysed for drug metabolites. Data over 2 years were compared using Wilcoxon matched-pair test. Data from 2010 festival were compared with data collected at the same time from a nearby urban community using equivalent methods. Conventional illicit drugs were detected in all samples whereas emerging illicit psychostimulants were found only on specific days. The estimated per capita consumption of MDMA, cocaine and cannabis was similar between the two festival years. Statistically significant (P popularity in music settings. Our study demonstrated that wastewater analysis can objectively capture changes in substance use at a music setting without raising major ethical issues. It would potentially allow effective assessments of drug prevention strategies in such settings in the future. © 2013 Australasian Professional Society on Alcohol and other Drugs.
drug resistant clinical and soil bacterial strains. Cinnamaldehyde was identified as the most active antimicrobial component present in the cinnamon essential oil which acted as a strong inhibitory agent in MIC assay against the tested bacteria. The results indicate that essential oils from Pakistani spices can be pursued against multidrug resistant bacteria. PMID:24119438
Murtaza, Ghulam; Ullah, Naveed; Mukhtar, Farah; Nawazish, Shamyla; Muneer, Saiqa
In herbalism, botanical supplements are commonly believed to be safe remedies, however, botanical supplements and dietary ingredients interact with transport and metabolic processes, affecting drug disposition. Although a large number of studies have described that botanical supplements interfere with drug metabolism, the mode of their interaction with drug transport processes is not well described. Such interactions may result in serious undesired effects and changed drug efficacy, therefore, some studies on interaction between botanical supplement ingredients and drug transporters such as P-gp and OATPs are described here, suggesting that the interaction between botanical supplements and the drug transporters is clinically significant.
Stokes, Matthew A R; Guest, Glenn D; Mamadi, Perista; Seta, Westin; Yaubihi, Noel; Karawiga, Grace; Naidi, Billy; Watters, David A K
Timely access to emergency and essential surgical care (EESC) and anaesthesia in low- and middle-income countries (LMICs) prevents premature death, minimises lifelong disability and reduces their economic impact on families and communities. Papua New Guinea is one of the poorest countries in the Pacific region, and provides much of its surgical care at a district hospital level. We aimed to evaluate the surgical capacity of a district hospital in PNG and estimate the effectiveness of surgical interventions provided. We performed a prospective study to calculate the number of DALYs averted for 465 patients treated with surgical care over a 3-month period (Sep-Nov 2013) in Alotau Hospital, Milne Bay Province, PNG (pop 210,000). Data were also collected on infrastructure, workforce, interventions provided and equipment available using the World Health Organization's Integrated Management of Emergency and Essential Surgical Care Toolkit, a survey to assess EESC and surgical capacity. We also performed a retrospective one-year audit of surgical, obstetric and anaesthetic care to provide context with regards to annual disease burden treated and surgical activity. EESC was provided by 11 Surgeons/Anaesthetists/Obstetricians (SAO) providers, equating to 5.7 per 100,000 population (including 4 nurse anaesthetists). They performed 783/100,000 procedures annually. Over the 3-month prospective study period, 4954 DALYs were averted by 465 surgical interventions, 52 % of which were elective. This equates to 18,330 DALYs averted annually or, approximately 18 % of the published but estimated disease burden in the Province in the 2013 Global Burden of Disease Study. The overall peri-operative mortality rate was 1.29 %, with 0.41 % for elective procedures and 2.25 % for emergencies. Much of the burden of surgical disease in Papua New Guinea presenting to Alotau General Hospital serving Milne Bay Province can be effectively treated by a small team providing emergency and
We investigated the combined antimicrobial effects of plant essential oils and olive extract against antibiotic resistant Salmonella enterica serovar Newport on organic leafy greens. Organic baby spinach, mature spinach, romaine lettuce, and iceberg lettuce were inoculated with S. Newport and dip-t...
Sharma, Gaurav; Oden, Neal; VanVeldhuisen, Paul C; Bogenschutz, Michael P
Secondary analysis using data from the National Drug Abuse Treatment Clinical Trials Network randomized trial (NCT # 01207791), in which 1285 adult ED patients endorsing moderate to severe problems related to drug use were recruited from 6 US academic hospitals. To investigate the utility of hair analysis in drug use disorder trials with infrequent visits, and its concordance with Timeline Follow Back (TLFB). This study compared the self-reported drug use on the TLFB instrument with the biological measure of drug use from hair analysis for four major drug classes (Cannabis, Cocaine, Prescribed Opioids and Street Opioids). Both hair analysis and TLFB were conducted at 3, 6 and 12 month follow-up visit and each covered a 90-day recall period prior to the visit. The concordance between the hair sample results and the TLFB was high for cannabis and street opioids, but was low to moderate for cocaine and prescribed opioids. Under-reporting of drug use given the positive hair sample was always significantly lower for the drug the study participant noted as their primary drug of choice compared with other drugs the participant reported taking, irrespective of whether the drug of choice was cannabis, cocaine, street opioids and prescribed opioids. Over-reporting of drug use given the negative hair sample was always significantly higher for the drug of choice, except for cocaine. This study extends the literature on hair analysis supporting its use as a secondary outcome measure in clinical trials. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Otávio de Tolêdo Nóbrega
Full Text Available OBJECTIVES: Price is a key obstacle for consumer access to essential drugs, especially in developing countries. This study sought to compare the retail prices of essential drugs on the private market in Brazil with that of two international pricing standards. METHODS: The retail price of all drugs on Brazil's Essential Drugs List, July 2000 edition, were compared to the retail price of the same drugs on the Swedish market and on a referential bulk-price indicator from low-cost suppliers on the international market. Ratios of Brazil's prices to Sweden's prices and Brazil's prices to the international bulk mean price-per-unit for each drug were calculated. Using linear regression analysis, the ratios were also studied in relation to the number of manufacturers. RESULTS: For the 132 drugs that were listed on both Brazil's and Sweden's lists, unitary retail prices in Brazil were 1.9 times higher. Of the 94 drugs found on both Brazil's list and the international unit-price indicator, Brazil's national mean unit prices were 13.1 more expensive. No relationship was found between the number of manufacturers for each product and the ratios of prices. CONCLUSIONS: Average retail prices of essential drugs in Brazil are significantly higher than in Sweden. Furthermore, international bulk prices indicate that drugs are brought to market by Brazil's private pharmacies at prices that may be excessively high in relation to production costs, creating high profit margins. The expected price-lowering effects of competition were not identified.OBJETIVO: Los precios constituyen un obstáculo clave para el acceso del consumidor a los medicamentos esenciales, especialmente en los países en desarrollo. El objetivo de este estudio fue comparar los precios minoristas de los medicamentos esenciales en el mercado privado de Brasil con los de dos estándares internacionales de precios. MÉTHODS: Se compararon los precios minoristas de todos los medicamentos de la Lista de
For generations, schools have routinely held fire drills. However, ensuring a safe learning environment is more complicated than staging an occasional drill. Schools and universities should have an integrated school safety plan, and it must address how to manage site hazards in science labs, kitchens and other building areas. It is essential for…
Geers, Bart; Dewitte, Heleen; De Smedt, Stefaan C; Lentacker, Ine
Time and space controlled drug delivery still remains a huge challenge in medicine. A novel approach that could offer a solution is ultrasound guided drug delivery. “Ultrasonic drug delivery” is often based on the use of small gas bubbles (so-called microbubbles) that oscillate and cavitate upon exposure to ultrasound waves. Some microbubbles are FDA approved contrast agents for ultrasound imaging and are nowadays widely investigated as promising drug carriers. Indeed, it has been observed that upon exposure to ultrasound waves, microbubbles may (a) release the encapsulated drugs and (b) simultaneously change the structure of the cell membranes in contact with the microbubbles which may facilitate drug entrance into cells. This review aims to highlight (a) major factors known so far which affect ultrasonic drug delivery (like the structure of the microbubbles, acoustic settings, etc.) and (b) summarizes the recent preclinical progress in this field together with a number of promising new concepts and applications.
Since 2004, the Subcommittee for Development of the National List of Essential Drugs (NLED) has embarked upon an historical evolution of applying evidence to the revision, inclusion and exclusion of medicines into and from the list. Then, the revision of the 2008 NLED was the first time in Thai history where the drug selection process in Thailand formally incorporated pharmacoeconomics. At present, the lack of a standard methodology for conducting economic evaluation is a major barrier that diminishes the potential use of economic evidence. The development of national economic evaluation guidelines by a group of national experts was subsequently endorsed by members in the Subcommittee as useful tools for future NLED revision. They emphasize that these guidelines should be applied not only to those evaluations conducted by public institutions but also by private pharmaceutical companies that often use this evidence for their marketing, or even for future requirements of economic information from industry, as complementary evidence for inclusion of health technology.
Gustafsson, Lars L; Wettermark, Björn; Godman, Brian; Andersén-Karlsson, Eva; Bergman, Ulf; Hasselström, Jan; Hensjö, Lars-Olof; Hjemdahl, Paul; Jägre, Ingrid; Julander, Margaretha; Ringertz, Bo; Schmidt, Daniel; Sjöberg, Susan; Sjöqvist, Folke; Stiller, Carl-Olav; Törnqvist, Elisabeth; Tryselius, Rolf; Vitols, Sigurd; von Bahr, Christer
The aim was to present and evaluate the impact of a comprehensive strategy over 10 years to select, communicate and achieve adherence to essential drug recommendations (EDR) in ambulatory care in a metropolitan healthcare region. EDRs were issued and launched as a 'Wise List' by the regional Drug and Therapeutics Committee in Stockholm. This study presents the concept by: (i) documenting the process for selecting, communicating and monitoring the impact of the 'Wise List'; (ii) analysing the variation in the number of drug substances recommended between 2000 and 2010; (iii) assessing the attitudes to the 'Wise List' among prescribers and the public; (iv) evaluating the adherence to recommendations between 2003 and 2009. The 'Wise List' consistently contained 200 drug substances for treating common diseases. The drugs were selected based on their efficacy, safety, suitability and cost-effectiveness. The 'Wise List' was known among one-third of a surveyed sample of the public in 2002 after initial marketing campaigns. All surveyed prescribers knew about the concept and 81% found the recommendations trustworthy in 2005. Adherence to recommendations increased from 69% in 1999 to 77% in 2009. In primary care, adherence increased from 83% to 87% from 2003 to 2009. The coefficient of variation (CV%) decreased from 6.1% to 3.8% for 156 healthcare centres between these years. The acceptance of the 'Wise List' in terms of trust among physicians and among the public and increased adherence may be explained by clear criteria for drug recommendations, a comprehensive communication strategy, electronic access to recommendations, continuous medical education and involvement of professional networks and patients.
Yao, Qiang; Liu, Chaojie; Ferrier, J Adamm; Liu, Zhiyong; Sun, Ju
To assess the impact of the National Essential Medicines Scheme (NEMS) with respect to urban-rural inequalities regarding drug prescriptions in primary care facilities. A stratified two-stage random sampling strategy was used to sample 23,040 prescriptions from 192 primary care facilities from 2009 to 2010. Difference-in-Difference (DID) analyses were performed to test the association between NEMS and urban-rural gaps in prescription patterns. Between-Group Variance and Theil Index were calculated to measure urban-rural absolute and relative disparities in drug prescriptions. The use of the Essential Medicines List (EML) achieved a compliance rate of up to 90% in both urban and rural facilities. An overall reduction of average prescription cost improved economic access to drugs for patients in both areas. However, we observed an increased urban-rural disparity in average expenditure per prescription. The rate of antibiotics and glucocorticoids prescription remained high, despite a reduced disparity between urban and rural facilities. The average incidence of antibiotic prescription increased slightly in urban facilities (62 to 63%) and reduced in rural facilities (67% to 66%). The urban-rural disparity in the use of parenteral administration (injections and infusions) increased, albeit at a high level in both areas (44%-52%). NEMS interventions are effective in reducing the overall average prescription costs. Despite the increased use of the EML, indicator performances with respect to rational drug prescribing and use remain poor and exceed the WHO/INRUD recommended cutoff values and worldwide benchmarks. There is an increased gap between urban and rural areas in the use of parenteral administration and expenditure per prescription.
Isaac Chun-Jen Chen
Conclusion: Although the prevalence of drug abuse-related accidents was low, and only three patient deaths were reported in this study, many patients presented to the EDs with severe effects and later required hospitalization. Better and timely management of such patients will help to minimize the adverse health impacts associated with drug abuse. Governmental agencies and all healthcare professionals should also work together to fight against the surging trend of drug abuse in Taiwan.
de Medeiros, Vivianne Marcelino; do Nascimento, Yuri Mangueira; Souto, Augusto Lopes; Madeiro, Sara Alves Lucena; Costa, Vicente Carlos de Oliveira; Silva, Suellen Maria P M; Falcão Silva, Vivyanne Dos Santos; Agra, Maria de Fátima; de Siqueira-Júnior, José Pinto; Tavares, Josean Fechine
The essential oil from leaves of Croton grewioides Baill was obtained by hydrodistillation using Clevenger apparatus, and its chemical composition was analyzed by GC-MS, where 18 compounds were identified, mostly as monoterpenes (55.56%) and sesquiterpenes (44.44%), in which the major constituent was the α-pinene (47.43%). The essential oil of Croton grewioides (EOCg) and its major compound (α-pinene) were evaluated as modulators of antibiotic resistance in strain SA-1199B and IS-58 of Staphylococcus aureus that overexpresses efflux protein. The minimum inhibitory concentrations (MICs) of the antibiotics were determined by the microdilution assay in the absence and in the presence of sub-inhibitory concentration of EOCg and α-pinene. Although the EOCg and α-pinene did not indicate relevant antibacterial activity in vitro, they acted as antibiotic resistance modulators, i.e., EOCg in combination with norfloxacin, reducted its MIC, by 64× whereas in combination with tetracycline it was observed a reduction of 4×. Additionally, it was observed a MIC reduction of tetracycline by 32×, when combined with α-pinene. The results suggest that EOCg and α-pinene modulate or even reverse bacterial resistance as a putative efflux pump inhibitor. Copyright © 2017 Elsevier Ltd. All rights reserved.
Full Text Available In this study, we retrospectively analysed a total of 605 clinical isolates from six West or Central African countries (Benin, Cameroon, Central African Republic, Guinea-Conakry, Niger and Senegal. Besides spoligotyping to assign isolates to ancient and modern mycobacterial lineages, we conducted phenotypic drug-susceptibility-testing for each isolate for the four first-line drugs. We showed that phylogenetically modern Mycobacterium tuberculosis strains are more likely associated with drug resistance than ancient strains and predict that the currently ongoing replacement of the endemic ancient by a modern mycobacterial population in West/Central Africa might result in increased drug resistance in the sub-region.
Leal, Wanda E; Jackson, Dylan B
The aim of the current study is to determine whether energy drink consumption contributes to drug use and, more specifically, an escalation in the severity of drug use. We first examine the association between energy drink use and hard drug use, and subsequently investigate whether soft drug use mediates this relationship. Potential moderating influences are also investigated by testing whether the degree of mediation varies by age, gender, and race. The current study uses a nationally representative sample of 8th (ages 13-14), 10th (ages 15-16), and 12th (ages 17-18) grade adolescents from the 2015 Monitoring the Future survey. Negative binomial regression is employed to examine associations between energy drink consumption and soft and hard drug use. Mediation results indicate that energy drink consumption is significantly associated with increased soft drug use, which is, in turn, associated with significant increases in hard drug use. This cascading effect of energy drink consumption on drug use appears to be stronger among younger females and older males. Results for the moderating effect of race are mixed. Energy drinks appear to pose an important threat to adolescent health in the form of soft and hard drug use. The United States may want to consider adopting energy drink policies similar to European countries and Canada, which require warning labels on beverages with high caffeine content. Copyright © 2017 Elsevier Inc. All rights reserved.
Alyaa M Abdel-Haleem
Full Text Available Several antimalarial drugs exist, but differences between life cycle stages among malaria species pose challenges for developing more effective therapies. To understand the diversity among stages and species, we reconstructed genome-scale metabolic models (GeMMs of metabolism for five life cycle stages and five species of Plasmodium spanning the blood, transmission, and mosquito stages. The stage-specific models of Plasmodium falciparum uncovered stage-dependent changes in central carbon metabolism and predicted potential targets that could affect several life cycle stages. The species-specific models further highlight differences between experimental animal models and the human-infecting species. Comparisons between human- and rodent-infecting species revealed differences in thiamine (vitamin B1, choline, and pantothenate (vitamin B5 metabolism. Thus, we show that genome-scale analysis of multiple stages and species of Plasmodium can prioritize potential drug targets that could be both anti-malarials and transmission blocking agents, in addition to guiding translation from non-human experimental disease models.
Abdel-Haleem, Alyaa M.
Several antimalarial drugs exist, but differences between life cycle stages among malaria species pose challenges for developing more effective therapies. To understand the diversity among stages and species, we reconstructed genome-scale models (GEMs) of metabolism for five life cycle stages and five species of Plasmodium spanning the blood, transmission, and mosquito stages. The stage-specific models of Plasmodium falciparum uncovered stage-dependent changes in central carbon metabolism and predicted potential targets that could affect several life cycle stages. The species-specific models further highlight differences between experimental animal models and the human-infecting species. Comparisons between human- and rodent-infecting species revealed differences in thiamine (vitamin B1), choline, and pantothenate (vitamin B5) metabolism. Thus, we show that genome-scale analysis of multiple stages and species of Plasmodium can prioritize potential drug targets that could be both anti-malarials and transmission blocking agents, in addition to guiding translation from non-human experimental disease models.
Cailhol, Lionel; Allen, Michael; Moncany, Anne-Hélène; Cicotti, Andrei; Virgillito, Salvatore; Barbe, Rémy P; Lazignac, Coralie; Damsa, Cristian
In spite of much effort to create guidelines on the management of violent behavior (VB) in emergency departments, little is known about the impact of such guidelines on a real-life emergency environment. The aim of this study is to investigate the impact of a staff educational crisis intervention (SECI) on the reduction of VB in patients admitted to emergency departments following drug suicidal attempt. The impact of a SECI on VB of patient consulting the ER following a drug suicide attempt was assessed by comparing the occurrence of VB before (5 months) and after (5 months) the introduction of a SECI. A significant reduction in VB (from 17.32% to 7.14%) was found with the comparison of two 5-month periods: before (254 patients) and after (224 patients) the introduction of a SECI program (chi(2)=11.238; P=.0008). These preliminary data suggest the need for further prospective randomized studies aiming to prevent VB in emergency departments by developing specific SECI programs.
Fallon, Stacie Alexander
The effects of drug and alcohol use by pregnant women which concern state policymakers are discussed in this booklet. Topics discussed include: (1) the effects of fetal alcohol syndrome on infants and children, as well as the effects on children of drug use by mothers during pregnancy; (2) initiatives aimed at helping these children; (3) women…
Halkitis, Perry N.; Manasse, Ashley N.; McCready, Karen C.
In this study we assess lifetime and recent drug use patterns among 261 heterosexually identified 18- to 25-year-olds through brief street intercept surveys conducted in New York City. Marijuana, hallucinogens, powder cocaine, and ecstasy were the most frequently reported drugs for both lifetime and recent use. Findings further suggest significant…
Roeloffzen, WWH; Verhaegh, JJ; van Poelgeest, AE; Gansevoort, RT
We describe two patients who developed granulocytopenia (granulocyte count <1.0 x 10(9)/l) after treatment with antithyroid drugs. Although, perhaps, an already known side-effect of these drugs, we present these cases in order to stay alert for this serious complication. The first patient developed
Singla, Sumeet K; Sachdeva, Vishal
Developing a transdermal drug delivery system is a challenging task considering the selective permeability of the skin and the physicochemical properties the drug must possess to permeate through the skin. Lipid-based drug delivery systems have contributed a great deal in this direction in the last few decades, and thereby have helped to expand the range of therapeutic molecules that can be delivered through the skin in a safe and effective manner. Additionally, vesicular delivery systems such as nanoparticles and emulsions have also played important roles in providing alternative novel approaches for drug delivery. In this article, we will discuss some of the current and future lipid-based systems for transdermal drug delivery along with the associated challenges.
Eichler, Hans-Georg; Bloechl-Daum, Brigitte; Abadie, Eric; Barnett, David; König, Franz; Pearson, Steven
Drug regulatory agencies have traditionally assessed the quality, safety and efficacy of drugs, and the current paradigm dictates that a new drug should be licensed when the benefits outweigh the risks. By contrast, third-party payers base their reimbursement decisions predominantly on the health benefits of the drug relative to existing treatment options (termed relative efficacy; RE). Over the past decade, the role of payers has become more prominent, and time-to-market no longer means time-to-licensing but time-to-reimbursement. Companies now have to satisfy the sometimes divergent needs of both regulators and payers, and to address RE during the pre-marketing stages. This article describes the current political background to the RE debate and presents the scientific and methodological challenges as they relate to RE assessment. In addition, we explain the impact of RE on drug development, and speculate on future developments and actions that are likely to be required from key players.
Oryan, A; Bemani, E; Bahrami, S
Leishmaniasis is a group of human and animal diseases causing 20,000 to 40,000 annual deaths and its etiological agents belong to the Leishmania genus. The most current treatment against leishmaniasis is chemotherapy. Pentavalent antimonials such as glucantime and pentostam have been administrated as the first-line drugs in treatment of various forms of leishmaniasis. The second-line drugs such as amphotericin B, liposomal amphotericin B, miltefosine, pentamidine, azole drugs and paromomycin are used in resistant cases to pentavalent antimonials. Because of drawbacks of the first-line and second-line drugs including adverse side effects on different organs, increasing resistance, high cost, need to hospitalization and long-term treatment, it is necessary to find an alternative drug for leishmaniasis treatment. Several investigations have reported the effectiveness of amiodarone, the most commonly used antiarrhythmic drug, against fungi, Trypanosomes and Leishmania spp. in vitro, in vivo and clinical conditions. Moreover, the beneficial effects of dronedarone, amiodarone analogues, against Trypanosoma cruzi and Leishmania mexicana have recently been demonstrated and such treatment regimens resulted in lower side effects. The anti- leishmanial and anti- trypanosomal effectiveness of amiodarone and dronedarone has been attributed to destabilization of intracellular Ca 2+ homeostasis, inhibition of sterol biosynthesis and collapse of mitochondrial membrane potential. Because of relative low cost, excellent pharmacokinetic properties, easy accessibility and beneficial effects of amiodarone and dronedarone on leishmaniasis, they are proper candidates to replace the current drugs used in leishmaniasis treatment. Copyright © 2018 Elsevier B.V. All rights reserved.
Lupattelli, Tommaso; Garaci, Francesco Giuseppe; Basile, Antonio; Minnella, Daniela Paola; Casini, Andrea; Clerissi, Jacques
Mycotic false aneurysm caused by local arterial injury from attempted intravenous injections in drug addicts remains a challenging clinical problem. The continued increase in drug abuse has resulted in an increased incidence of this problem, particularly in high-volume urban centres. In the drug-abusing population, mycotic arterial pseudoaneurysms most often occur because of missed venous injection and are typically seen in the groin, axilla, and antecubital fossa. Mycotic aneurysms may lead to life-threatening haemorrhage, limb loss, sepsis, and even death. Any soft-tissue swelling in the vicinity of a major artery in an intravenous drug abuser should be suspected of being a false aneurysm until proven otherwise and should prompt immediate referral to a vascular surgeon for investigation and management. We report a case of rupturing mycotic pseudoaneurysm of the left common femoral artery treated by surgical resection followed by vessel reconstruction with autologous material. Unfortunately, at the time of discharge a sudden leakage from the vein graft anastomosis occurred, with subsequent massive bleeding, and required emergent endovascular covered stenting. To the best of our knowledge, this is the first reported case of femoral artery bleeding in a drug abuser treated by stent graft placement.
Ruiz-Colón, Kazandra; Chavez-Arias, Carlos; Díaz-Alcalá, José Eric; Martínez, María A
Xylazine is not a controlled substance; it is marketed as a veterinary drug and used as a sedative, analgesic and muscle relaxant. In humans, it could cause central nervous system depression, respiratory depression, bradycardia, hypotension, and even death. There have been publications of 43 cases of xylazine intoxication in humans, in which 21 (49%) were non-fatal scenarios and 22 (51%) resulted in fatalities. Most of the non-fatal cases required medical intervention. Over recent years xylazine has emerged as an adulterant in recreational drugs, such as heroin or speedball (a cocaine and heroin mixture). From the 43 reported cases, 17 (40%) were associated with the use of xylazine as an adulterant of drugs of abuse. Its chronic use is reported to be associated with physical deterioration and skin ulceration. Literature shows some similar pharmacologic effects between xylazine and heroin in humans. These similar pharmacologic effects may create synergistic toxic effects in humans. Therefore, fatalities among drug users may increase due to the use of xylazine as an adulterant. Xylazine alone has proven harmful to humans and even more when it is combined with drugs of abuse. A comprehensive review of the literature of non-fatal and fatal xylazine intoxication cases including those in which the substance was used as adulterant is presented, in order to increase the awareness in the forensic community, law enforcement, and public health agencies. Published by Elsevier Ireland Ltd.
Full Text Available Despite relevant progress obtained by multimodal treatment, glioblastoma (GBM, the most aggressive primary brain tumor, is still incurable. The most encouraging advancement of GBM drug research derives from the identification of cancer stem cells (CSCs, since these cells appear to represent the determinants of resistance to current standard therapies. The goal of most ongoing studies is to identify drugs able to affect CSCs biology, either inducing selective toxicity or differentiating this tumor cell population into nontumorigenic cells. Moreover, the therapeutic approach for GBM could be improved interfering with chemo- or radioresistance mechanisms, microenvironment signals, and the neoangiogenic process. During the last years, molecular targeted compounds such as sorafenib and old drugs, like metformin, displayed interesting efficacy in preclinical studies towards several tumors, including GBM, preferentially affecting CSC viability. In this review, the latest experimental results, controversies, and prospective application concerning these promising anticancer drugs will be discussed.
de Almeida, Tânia Santos; Júlio, Ana; Mota, Joana Portugal; Rijo, Patrícia; Reis, Catarina Pinto
There is a growing need to develop drug-delivery systems that overcome drawbacks such as poor drug solubility/loading/release, systemic side effects and limited stability. Ionic liquids (ILs) offer many advantages and their tailoring represents a valuable tuning tool. Nano-based systems are also prized materials that prevent drug degradation, enhance their transport/distribution and extend their release. Consequently, structures containing ILs and nanoparticles (NPs) have been developed to attain synergistic effects. This overview on the properties of ILs, NPs and of their combined structures, reveals the recent advances in these areas through a review of pertinent literature. The IL-NP structures present enhanced properties and the subsequent performance upgrade proves to be useful in drug delivery, although much is yet to be done.
mail: firstname.lastname@example.org. 2014, a total of 497 illicit ... knowledgeable of current trends. The prevalence ... use or addiction only to alcohol, cigarettes, or inhaled ... were searched for admission to drug abuse and treatment.
Katselou, Maria; Papoutsis, Ioannis; Nikolaou, Panagiota; Spiliopoulou, Chara; Athanaselis, Sotiris
"Krokodil" is the street name for the semi-synthetic opioid derivative desomorphine. Although an old drug, it re-staged on "drug arena" during the last decade causing detrimental effects to its users. Despite the fact that Russia and other former Soviet Republics were the initial plagued countries, "krokodil" arrived in Europe and United States lately, as a substitute of the relative expensive, and in many cases unavailable, heroin. It can be easily manufactured in home-environment from codeine and causes significant health problems, even deaths worldwide. The aim of this review is to summarize the current knowledge about this drug, concerning its chemistry, synthesis, pharmacology and toxicology. Published or reported "krokodil" related cases, fatalities or intoxications, as well as self reports from drug users are reviewed. The existing analytical methodologies for the determination of desomorphine in biological samples as well as its legal status are also presented. Copyright © 2014 Elsevier Inc. All rights reserved.
Full Text Available Glioblastoma multiforme (GBM is a grade IV astrocytoma and the most common malignant brain tumor. Current therapies provide a median survival of 12–15 months after diagnosis, due to the high recurrence rate. The failure of current therapies may be due to the presence, within the tumor, of cells characterized by enhanced self-renewal capacity, multilineage differentiation potential and elevated invasive behavior, called glioma stem cells (GSCs. To evaluate the pharmacological efficacy of selected drugs on six GSC lines, we set up a multiple drug responsivity assay based on the combined evaluation of cytomorphological and functional parameters, including the analysis of polymorphic nuclei, mitotic index and cell viability. In order to understand the real pharmacological efficacy of the tested drugs, we assigned a specific drug responsivity score to each GSC line, integrating the data produced by multiple assays. In this work we explored the antineoplastic effects of paclitaxel (PTX, an inhibitor of microtubule depolymerization, utilized as standard treatment in several cancers, and of valproic acid (VPA, an inhibitor of histone deacetylases (HDACs with multiple anticancer properties. We classified the six GSC lines as responsive or resistant to these drugs, on the basis of their responsivity scores. This method can also be useful to identify the best way to combine two or more drugs. In particular, we utilized the pro-differentiating effect of VPA to improve the PTX effectiveness and we observed a significant reduction of cell viability compared to single treatments.
Brandt, L.; Anderson, H. [University Hospital, Department of Oncology and Southern Swedish Regional Rumour Registry, Lund (Sweden)
For 366 patients with polycythaemia vera (PV) or essential thrombocythaemia (ET) diagnosed 1971-1990, oral administration of 32-P was used as myelosuppressive treatment. Retreatment was not restricted to any defined interval and the number of treatments or the total dose were not limited. For 107 patients, follow-up was > 10 years. 15 of these presented with life-threatening occlusive vascular symptoms and their survival was short. For the remaining 92 patients 5-yr survival was not significantly worse than for a Swedish population matched for age and sex. Survival at 10 yr was lower, 51% versus 66% expected. Acute myeloid leukaemia (AML) was diagnosed in 11 of the 107 patients (10.3%). In the whole material of 366 patients, 17 have developed AML with a median time of 8.5 yr from start of treatment. There was a maximum incidence of 4% per yr after 8-12 yr. Later, the incidence decreased. The median annual dose of 32-P for the AML patients was 100 MBq and was not significantly larger than for a matched control group surviving without AML, 95 MBq. The results are compared with reports on PV or ET patients treated with busulphan (Bu) or hydroxyurea (HU). With comparable periods of follow-up there are no indications that an adequate myelosuppression with oral 32-P will be associated with shorter survival or higher incidence of AML than treatment with Bu or HU. It is concluded that, for the time being, oral administration of 32-P is an acceptable standard treatment in PV and ET. (au) (20 refs.).
Hock, Rebecca S.; Hindin, Michelle J.; Bass, Judith K.; Surkan, Pamela J.; Bradshaw, Catherine P.; Mendelson, Tamar
Parenting style is a potent and malleable influence on emerging adult substance use. Most of the parenting-substance use literature has been conducted in Western populations and it is unknown whether findings are generalizable to other cultures and contexts. We extended the parenting-substance use literature to a cohort of emerging adults in the Philippines using the Cebu Longitudinal Health and Nutrition Survey. We assessed associations between mothers’ and fathers’ parenting styles (authori...
Calle, Paul; Sundahl, Nora; Maudens, Kristof; Wille, Sarah Mr; Van Sassenbroeck, Diederik; De Graeve, Koen; Gogaert, Stefan; De Paepe, Peter; Devriese, Dieter; Arno, Geert; Blanckaert, Peter
clinical presentations were rather mild. It should be stressed that these observations only apply to this particular event and cannot be generalized to other EDM events. Calle P , Sundahl N , Maudens K , Wille SMR , Van Sassenbroeck D , De Graeve K , Gogaert S , De Paepe P , Devriese D , Arno G , Blanckaert P . Medical emergencies related to ethanol and illicit drugs at an annual, nocturnal, indoor, electronic dance music event. Prehosp Disaster Med. 2018;33(1):71-76.
What started as a trickle of new agents that help the body's immune system fight cancer has now become a flood, despite some daunting adverse effects. This report discusses the new drugs, indications, and combinations that continue to emerge.
Poulsen, Nina Rødtness
in multi-drug-resistant PRs. Computational analysis of a vast number of inhibitor-resistant HIV-1 PR variants can broaden the knowledge of how and why the mutations arise, which would be a great advantage in the design on resistance-evading inhibitors. Here we present a diverse system to select...... in the virus life cycle has made it a major target for drug development and active site competitive inhibitors have been successful in the battle against HIV. Unfortunately, the massive drug pressure along with high-level replication and lack of proofreading by the viral reverse transcriptase have resulted...... for catalytically active HIV-1 PR in the presence of inhibitor. The system is based on the protein AraC, which regulates transcription of the araA, araB and araD genes necessary for arabinose catabolism in Escherichia coli, and its effectiveness was demonstrated by the isolation of both known and unknown inhibitor-resistant...
Full Text Available The emergence of endocrine disease has created significant challenges for healthcare policy-makers and payers across the world. Policy-makers have to ensure availability of drugs used for various endocrinopathies. One way in which this is facilitated is through the World Health Organization (WHO List of Essential Medicines (LEM. The LEM aims to cover the basic pharmaceutical needs of the majority of people seeking healthcare (1.
controlled devices provide advantages over passive release devices, as the drug delivery process can be controlled actively after implantation and...mm, 5 μm, 100 Å, Alltech Associates, USA), with methanol and 0.1% trifluoroacetic acid (TFA) in water. The gradient used was 2 % TFA/min, starting
Objectives: To examine the prevalence of alcohol and drug use and abuse, to identify socio-demographic characteristics that correlated with injury and to identify risk factors for injury in a Nigerian Trauma unit. Design: Descriptive cross sectional study. Setting: The study was carried out a general hospital trauma unit in ...
Fu, Rong-Geng; Sun, Yuan; Sheng, Wen-Bing; Liao, Duan-Fang
The dominant paradigm in drug discovery is to design ligands with maximum selectivity to act on individual drug targets. With the target-based approach, many new chemical entities have been discovered, developed, and further approved as drugs. However, there are a large number of complex diseases such as cancer that cannot be effectively treated or cured only with one medicine to modulate the biological function of a single target. As simultaneous intervention of two (or multiple) cancer progression relevant targets has shown improved therapeutic efficacy, the innovation of multi-targeted drugs has become a promising and prevailing research topic and numerous multi-targeted anticancer agents are currently at various developmental stages. However, most multi-pharmacophore scaffolds are usually discovered by serendipity or screening, while rational design by combining existing pharmacophore scaffolds remains an enormous challenge. In this review, four types of multi-pharmacophore modes are discussed, and the examples from literature will be used to introduce attractive lead compounds with the capability of simultaneously interfering with different enzyme or signaling pathway of cancer progression, which will reveal the trends and insights to help the design of the next generation multi-targeted anticancer agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Wang, Junyong; Liu, Xia; Wang, Suzhen; Chen, Heli; Wang, Xun; Zhou, Wei; Wang, Li; Zhu, Yanchen; Zheng, Xianping; Hao, Mo
China's 2009 national essential medicine system (NEMS) was designed to reduce prices through a zero-markup policy and a centralized bidding system. To analyze NEMS's short-term impact on drug prices, we estimated the retail and wholesale prices before and after the reform at health institutions in rural Jiangxi Province. We undertook two cross-sectional surveys of prices of 39 medicines in November 2008 and May 2010, calculated inflation adjusted prices, and used the Wilcoxon signed-rank and rank-sum tests to examine price changes at different health institutions. Retail prices at pilot (P health centers decreased significantly, whereas the declines at retail pharmacies (P = 0.57) and village clinics (P = 0.29) were insignificant. The decline at pilot township health centers was the largest, compared with other kinds of health institutions (P health institutions, the centralized bidding system was insufficient to lower wholesale prices. A drug price management system should be constructed to control medicine prices and a long-term price information system is needed to monitor price changes.
Evaluation of the use of partition coefficients and molecular surface properties as predictors of drug absorption: a provisional biopharmaceutical classification of the list of national essential medi
Full Text Available Background and the purpose of the study: Partition coefficients (log D and log P and molecular surface area (PSA are potential predictors of the intestinal permeability of drugs. The aim of this investigation was to evaluate and compare these intestinal permeability indicators. Methods: Aqueous solubility data were obtained from literature or calculated using ACD/Labs and ALOGPS. Permeability data were predicted based on log P, log D at pH 6.0 (log D6.0, and PSA. Results: Metoprolol's log P, log D6.0 and a PSA of <65 Å correctly predicted 55.9%, 50.8% and 54.2% of permeability classes, respectively. Labetalol's log P, log D6.0, and PSA correctly predicted 54.2%, 64.4% and 61% of permeability classes, respectively. Log D6.0 correlated well (81% with Caco-2 permeability (Papp. Of the list of national essential medicines, 135 orally administered drugs were classified into biopharmaceutical classification system (BCS. Of these, 57 (42.2%, 28 (20.7%, 44 (32.6%, and 6 (4.4% were class I, II, III and IV respectively. Conclusion: Log D6.0 showed better prediction capability than log P. Metoprolol as permeability internal standard was more conservative than labetalol.
Zhou, Zhongliang; Su, Yanfang; Campbell, Benjamin; Zhou, Zhiying; Gao, Jianmin; Yu, Qiang; Chen, Jiuhao; Pan, Yishan
With a quasi-experimental design, this study aims to assess whether the Zero-markup Policy for Essential Drugs (ZPED) reduces the medical expense for patients at county hospitals, the major healthcare provider in rural China. Data from Ningshan county hospital and Zhenping county hospital, China, include 2014 outpatient records and 9239 inpatient records. Quantitative methods are employed to evaluate ZPED. Both hospital-data difference-in-differences and individual-data regressions are applied to analyze the data from inpatient and outpatient departments. In absolute terms, the total expense per visit reduced by 19.02 CNY (3.12 USD) for outpatient services and 399.6 CNY (65.60 USD) for inpatient services. In relative terms, the expense per visit was reduced by 11% for both outpatient and inpatient services. Due to the reduction of inpatient expense, the estimated reduction of outpatient visits is 2% among the general population and 3.39% among users of outpatient services. The drug expense per visit dropped by 27.20 CNY (4.47 USD) for outpatient services and 278.7 CNY (45.75 USD) for inpatient services. The proportion of drug expense out of total expense per visit dropped by 11.73 percentage points in outpatient visits and by 3.92 percentage points in inpatient visits. Implementation of ZPED is a benefit for patients in both absolute and relative terms. The absolute monetary reduction of the per-visit inpatient expense is 20 times of that in outpatient care. According to cross-price elasticity, the substitution between inpatient and outpatient due to the change in inpatient price is small. Furthermore, given that the relative reductions are the same for outpatient and inpatient visits, according to relative thinking theory, the incentive to utilize outpatient or inpatient care attributed to ZPED is equivalent, regardless of the 20-times price difference in absolute terms.
Full Text Available With a quasi-experimental design, this study aims to assess whether the Zero-markup Policy for Essential Drugs (ZPED reduces the medical expense for patients at county hospitals, the major healthcare provider in rural China.Data from Ningshan county hospital and Zhenping county hospital, China, include 2014 outpatient records and 9239 inpatient records. Quantitative methods are employed to evaluate ZPED. Both hospital-data difference-in-differences and individual-data regressions are applied to analyze the data from inpatient and outpatient departments.In absolute terms, the total expense per visit reduced by 19.02 CNY (3.12 USD for outpatient services and 399.6 CNY (65.60 USD for inpatient services. In relative terms, the expense per visit was reduced by 11% for both outpatient and inpatient services. Due to the reduction of inpatient expense, the estimated reduction of outpatient visits is 2% among the general population and 3.39% among users of outpatient services. The drug expense per visit dropped by 27.20 CNY (4.47 USD for outpatient services and 278.7 CNY (45.75 USD for inpatient services. The proportion of drug expense out of total expense per visit dropped by 11.73 percentage points in outpatient visits and by 3.92 percentage points in inpatient visits.Implementation of ZPED is a benefit for patients in both absolute and relative terms. The absolute monetary reduction of the per-visit inpatient expense is 20 times of that in outpatient care. According to cross-price elasticity, the substitution between inpatient and outpatient due to the change in inpatient price is small. Furthermore, given that the relative reductions are the same for outpatient and inpatient visits, according to relative thinking theory, the incentive to utilize outpatient or inpatient care attributed to ZPED is equivalent, regardless of the 20-times price difference in absolute terms.
Liakoni, Evangelia; Dolder, Patrick C; Rentsch, Katharina; Liechti, Matthias E
To describe acute toxicity of recreational drugs including novel psychoactive substances. We included all cases presenting at the emergency department (ED) of the University Hospital of Basel, Switzerland, between October 2013 and September 2014 with acute toxicity due to self-reported recreational drug use or with symptoms/signs consistent with acute toxicity. Isolated ethanol intoxications were excluded. Intoxications were confirmed with immunoassays and liquid chromatography coupled with mass spectrometry (LC-MS/MS), which also detected novel psychoactive substances. Among the 47,767 attendances at the ED, 216 were directly related to acute toxicity of recreational drugs. The mean patient age was 31 years and 69% were male. Analytical drug confirmation was available in 180 cases. Most presentations were related to cocaine (36%), cannabis (31%), opioids (13%), 3,4-methylenedioxy-methamphetamine (MDMA, 9%), other amphetamines (7%), benzodiazepines (7%), and lysergic acid diethylamide (LSD, 5%). The substances most commonly detected analytically were cannabis (37%), cocaine (33%), opioids (29%), benzodiazepines (21%), and amphetamines including MDMA (13%). Notably, there were only two cases of novel psychoactive substances (2,5-dimethoxy-4-bromophenethylamine [2C-B] and pentylone). The most frequent symptoms were tachycardia (31%), anxiety (27%), nausea or vomiting (23%), and agitation (22%). Severe complications included myocardial infarction (2), psychosis (10), seizures (10), and 1 fatality. Most patients were discharged home (68%), 8% were admitted to intensive care and 9% were referred to psychiatric care. Medical problems related to illicit drugs mostly concerned cocaine and cannabis and mainly involved sympathomimetic toxicity and/or psychiatric disorders. ED presentations associated with novel psychoactive substances appeared to be relatively rare.
Anjali Joshi* and Ganesh Kumar
Various pharmaceutical dosage form are present in the market but all of the dosage forms possess some drawback most common is patient incompliance which is seen in all age groups. So from last few years focus is done on developing such dosage form which enhances safety, efficacy and patient compliance. In this manner, in late 1970 fast-dissolving drug delivery system came in existence which includes Fast dissolving tablets and fast dissolving thin strips means those dosage form which dissolve...
Gregory Charles Sartor
Full Text Available Prolonged drug use causes long-lasting neuroadaptations in reward-related brain areas that contribute to addiction. Despite significant amount of research dedicated to understanding the underlying mechanisms of addiction, the molecular underpinnings remain unclear. At the same time, much of the pervasive transcription that encompasses the human genome occurs in the nervous system and contributes to its heterogeneity and complexity. Recent evidence suggests that non-coding RNAs (ncRNAs play an important and dynamic role in transcriptional regulation, epigenetic signaling, stress response, and plasticity in the nervous system. Dysregulation of ncRNAs are thought to contribute to many, and perhaps all, neurological disorders, including addiction. Here, we review recent insights in the functional relevance of ncRNAs, including both microRNAs (miRNAs and long non-coding RNAs (lncRNAs, and then illustrate specific examples of ncRNA regulation in the context of drug addiction. We conclude that ncRNAs are importantly involved in the persistent neuroadaptations associated with addiction-related behaviors, and that therapies that target specific ncRNAs may represent new avenues for the treatment of drug addiction.
Aliza K. De Nobrega
Full Text Available Endogenous circadian oscillators orchestrate rhythms at the cellular, physiological, and behavioral levels across species to coordinate activity, for example, sleep/wake cycles, metabolism, and learning and memory, with predictable environmental cycles. The 21st century has seen a dramatic rise in the incidence of circadian and sleep disorders with globalization, technological advances, and the use of personal electronics. The circadian clock modulates alcohol- and drug-induced behaviors with circadian misalignment contributing to increased substance use and abuse. Invertebrate models, such as Drosophila melanogaster, have proven invaluable for the identification of genetic and molecular mechanisms underlying highly conserved processes including the circadian clock, drug tolerance, and reward systems. In this review, we highlight the contributions of Drosophila as a model system for understanding the bidirectional interactions between the circadian system and the drugs of abuse, alcohol and cocaine, and illustrate the highly conserved nature of these interactions between Drosophila and mammalian systems. Research in Drosophila provides mechanistic insights into the corresponding behaviors in higher organisms and can be used as a guide for targeted inquiries in mammals.
Full Text Available One of the most important therapeutic advances obtained in the field of rheumatology is the availability of the so-called bio(technological drugs, which have deeply changed treatment perspectives in diseases such as rheumatoid arthritis and ankylosing spondylitis. According to the steadily increasing attention on gout, due to well-established prognostic and epidemiology implications, in the last 5 years, the same change of perspective has been observed also for this disease. In fact, several bio(technological agents have been investigated both for the management of the articular gout symptoms, targeting mainly interleukin-1β, as well as urate-lowering therapies such as recombinant uricases. Among the IL-1β inhibitors, the majority of studies involve drugs such as anakinra, canakinumab, and rilonacept, but other compounds are under development. Moreover, other potential targets have been suggested, as, for example, the TNF alpha and IL-6, even if data obtained are less robust than those of IL-1β inhibitors. Regarding urate-lowering therapies, the recombinant uricases pegloticase and rasburicase clearly showed their effectiveness in gout patients. Also in this case, new compounds are under development. The aim of this review is to focus on the various aspects of different bio(technological drugs in gouty patients.
Gaber, Mohamed; Medhat, Waseem; Hany, Mark; Saher, Nourhan; Fang, Jia-You; Elzoghby, Ahmed
Nanoparticulate drug delivery systems have been long used to deliver a vast range of drugs and bioactives owing to their ability to demonstrate novel physical, chemical, and/or biological properties. An exponential growth has spurred in research and development of these nanocarriers which led to the evolution of a great number of diverse nanosystems including liposomes, nanoemulsions, solid lipid nanoparticles (SLNs), micelles, dendrimers, polymeric nanoparticles (NPs), metallic NPs, and carbon nanotubes. Among them, lipid-based nanocarriers have made the largest progress whether commercially or under development. Despite this progress, these lipid-based nanocarriers suffer from several limitations that led to the development of many protein-coated lipid nanocarriers. To less extent, protein-based nanocarriers suffer from limitations that led to the fabrication of some lipid bilayer enveloping protein nanocarriers. This review discusses in-depth some limitations associated with the lipid-based or protein-based nanocarriers and the fruitful outcomes brought by protein-lipid hybridization. Also discussed are the various hybridization techniques utilized to formulate these protein-lipid nanohybrids and the mechanisms involved in the drug loading process. Copyright © 2017 Elsevier B.V. All rights reserved.
Arias Constantí, Vanessa; Sanz Marcos, Nuria; Trenchs Sainz de La Maza, Victoria; Curcoy Barcenilla, Ana I; Matalí Costa, Josep; Luaces Cubells, Carles
To describe psychoactive substances (PS)-related visits of adolescents to the emergency department and to explore possible differential features in patients according to the kind of PS consumed. Observational and analytic study. PS-related visits of adolescents to the emergency department during 30 months were studied. Patients were divided in two groups: those with alcohol intoxication only (Group_1) and those with other PS (Group_2) and they were compared. 333 consults were included, corresponding to 321 patients. Their mean age was 16,1 years (SD:1,1 years). Two hundred sixty-two(78,7%) were alcohol-related visits, and 110(33%) were related with another PS consumption. Of the 262 alcohol-related visits, 223 were only related with alcohol(Group_1), while the other 110 visits made up Group_2. Group_2 was composed of more males, more adolescents placed in Institutional Care and more adolescents with psychiatric records than Group_1. Likewise, distribution of Group_2 visits was less predictable than distribution of Group_1. PS consumption is a frequent major complaint in an Emergency Department. There are more poly-intoxications in males with psycho-social problems. In those cases, consumption seems to happen regardless of the time in the day or the day of the week.
Full Text Available Background: During times of fiscal austerity, means of reimbursement decision-making are of particular interest for public health theory and practice. Introduction of advanced health technologies, growing health expenditures and increased public scrutiny over drug reimbursement decisions have pushed governments to consider mechanisms that promote the use of effective health technologies, while constraining costs. Aims: The study’s aim was to explore the current rationale of the drug reimbursement decision-making framework in Bulgaria. Our pilot research focused on one particular component of this process – the criteria used – because of the critical role that criteria are known to have in setting budgets and priorities in the field of public health. The analysis pursued two objectives: to identify important criteria relevant to drug reimbursement decision-making and to unveil relationships between theory and practice. Study Design: Cross-sectional study. Methods: The study was realized through a closed-ended survey on reimbursement criteria among four major public health stakeholders – medical professionals, patients, health authorities, and industry. Empirical outcomes were then cross-compared with the theoretical framework, as defined by current Bulgarian public health legislation. Analysis outlined what is done and what needs to be done in the field of public health reimbursement decision-making. Results: Bulgarian public health stakeholders agreed on 15 criteria to form a tentative optimal framework for drug reimbursement decision-making. The most apparent gap between the empirically found preferences and the official legislation is the lack of consideration for the strength of evidence in reimbursement decisions. Conclusion: Bulgarian policy makers need to address specific gaps, such as formal consideration for strength of evidence, explicit role of efficiency criteria, and means to effectively empower patient and citizen
... Emergency 101 Share this! Home » Emergency 101 Is it an Emergency? Medical emergencies can be frightening and ... situation. Here you can find information about emergencies. It is essential to know how to recognize the ...
Full Text Available The improvement of food preservation by using essential oils (EOs and their individual constituents (ICs is attracting enormous interest worldwide. Until now, researchers considered that treatments with such antimicrobial compounds did not induce bacterial resistance via a phenotypic (i.e. transient response. Nevertheless, the emergence of genotypic (i.e. stable resistance after treatment with these compounds had not been previously tested. Our results confirm that growth of Escherichia coli MG1655 in presence of sub-inhibitory concentrations of the ICs carvacrol, citral, and (+-limonene oxide do not increase resistance to further treatments with either the same IC (direct resistance or with other preservation treatments (cross-resistance such as heat or pulsed electric fields (PEF. Bacterial mutation frequency was likewise lower when those IC’s were applied; however, after 10 days of re-culturing cells in presence of sub-inhibitory concentrations of the ICs, we were able to isolate several derivative strains (i.e. mutants displaying an increased minimum inhibitory concentration to those ICs. Furthermore, when compared to the wild type (WT strain, they also displayed direct resistance and cross-resistance. Derivative strains selected with carvacrol and citral also displayed morphological changes involving filamentation along with cell counts at late-stationary growth phase that were lower than the WT strain. In addition, co-cultures of each derivative strain with the WT strain resulted in a predominance of the original strain in absence of ICs, indicating that mutants would not out-compete WT cells under optimal growth conditions. Nevertheless, growth in the presence of ICs facilitated the selection of these resistant mutants. Thus, as a result, subsequent food preservation treatments of these bacterial cultures might be less effective than expected for WT cultures. In conclusion, this study recommends that treatment with ICs at sub
Chueca, Beatriz; Berdejo, Daniel; Gomes-Neto, Nelson J; Pagán, Rafael; García-Gonzalo, Diego
The improvement of food preservation by using essential oils (EOs) and their individual constituents (ICs) is attracting enormous interest worldwide. Until now, researchers considered that treatments with such antimicrobial compounds did not induce bacterial resistance via a phenotypic (i.e., transient) response. Nevertheless, the emergence of genotypic (i.e., stable) resistance after treatment with these compounds had not been previously tested. Our results confirm that growth of Escherichia coli MG1655 in presence of sub-inhibitory concentrations of the ICs carvacrol, citral, and (+)-limonene oxide do not increase resistance to further treatments with either the same IC (direct resistance) or with other preservation treatments (cross-resistance) such as heat or pulsed electric fields (PEF). Bacterial mutation frequency was likewise lower when those IC's were applied; however, after 10 days of re-culturing cells in presence of sub-inhibitory concentrations of the ICs, we were able to isolate several derivative strains (i.e., mutants) displaying an increased minimum inhibitory concentration to those ICs. Furthermore, when compared to the wild type (WT) strain, they also displayed direct resistance and cross-resistance. Derivative strains selected with carvacrol and citral also displayed morphological changes involving filamentation along with cell counts at late-stationary growth phase that were lower than the WT strain. In addition, co-cultures of each derivative strain with the WT strain resulted in a predominance of the original strain in absence of ICs, indicating that mutants would not out-compete WT cells under optimal growth conditions. Nevertheless, growth in the presence of ICs facilitated the selection of these resistant mutants. Thus, as a result, subsequent food preservation treatments of these bacterial cultures might be less effective than expected for WT cultures. In conclusion, this study recommends that treatment with ICs at sub
Full Text Available Introduction: Annually eight million emergency department (ED visits are attributable to alcohol use. Screening ED patients for at-risk alcohol and substance use is an integral component of screening, brief intervention, and referral to treatment programs, shown to be effective at reducing substance use. The objective is to evaluate ED patients’ acceptance of and willingness to disclose alcohol/substance use via a computer kiosk versus an in-person interview. Methods: This was a cross-sectional, survey-based study. Eligible participants included those who presented to walk-in triage, were English-speaking, ≥18 years, were clinically stable and able to consent. Patients had the opportunity to access the kiosk in the ED waiting room, and were approached for an in-person survey by a research assistant (9am-5pm weekdays. Both surveys used validated assessment tools to assess drug and alcohol use. Disclosure statistics and preferences were calculated using chi-square tests and McNemar’s test. Results: A total of 1,207 patients were screened: 229 in person only, 824 by kiosk, and 154 by both in person and kiosk. Single-modality participants were more likely to disclose hazardous drinking (p=0.003 and high-risk drug use (OR=22.3 [12.3-42.2]; p<0.0001 via kiosk. Participants who had participated in screening via both modalities were more likely to reveal high-risk drug use on the kiosk (p=0.003. When asked about screening preferences, 73.6% reported a preference for an in-person survey, which patients rated higher on privacy and comfort. Conclusion: ED patients were significantly more likely to disclose at-risk alcohol and substance use to a computer kiosk than an interviewer. Paradoxically patients stated a preference for in-person screening, despite reduced disclosure to a human screener. [West J Emerg Med. 2015;16(2:220–228.
Full Text Available Better the drugs you know than the drugs you do not know. Drug repurposing is a promising, fast, and cost effective method that can overcome traditional de novo drug discovery and development challenges of targeting neuropsychiatric and other disorders. Drug discovery and development targeting neuropsychiatric disorders are complicated because of the limitations in understanding pathophysiological phenomena. In addition, traditional de novo drug discovery and development are risky, expensive, and time-consuming processes. One alternative approach, drug repurposing, has emerged taking advantage of off-target effects of the existing drugs. In order to identify new opportunities for the existing drugs, it is essential for us to understand the mechanisms of action of drugs, both biologically and pharmacologically. By doing this, drug repurposing would be a more effective method to develop drugs against neuropsychiatric and other disorders. Here, we review the difficulties in drug discovery and development in neuropsychiatric disorders and the extent and perspectives of drug repurposing.
Torne, Sangmesh Raosaheb; Sheela, Angappan; Sarada, N C
The oral liquid drug delivery system (OLDDS) remains as the primary choice of dosage form, though challenging, for the pharmaceutical scientists. In the last two decades, Oral Liquid Controlled Release (OLCR) formulation has gained a lot of attention because of its advantages over the conventional dosage forms. The world of nanotechnology has paved multiple ways to administer the drug through oral cavity in liquid dosage form with an additional advantage of control over the release. In the current study, the various approaches towards the same have been discussed comprehensively to understand the different mechanisms of OLCR. This review also emphasizes on the existing techniques and the developments that have been made to improve on its efficacy including various formulation related factors. It also provides valuable insights into the role of polymers in the development of OLCR formulation that can be used in the management of Gastroesophageal reflux disease (GERD). Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Full Text Available Streptococcus suis, a major porcine pathogen, has been receiving growing attention not only for its role in severe and increasingly reported infections in humans, but also for its involvement in drug resistance. Recent studies and the analysis of sequenced genomes have been providing important insights into the S. suis resistome, and have resulted in the identification of resistance determinants for tetracyclines, macrolides, aminoglycosides, chloramphenicol, antifolate drugs, streptothricin, and cadmium salts. Resistance gene-carrying genetic elements described so far include integrative and conjugative elements, transposons, genomic islands, phages, and chimeric elements. Some of these elements are similar to those reported in major streptococcal pathogens such as Streptococcus pyogenes, Streptococcus pneumoniae, and Streptococcus agalactiae and share the same chromosomal insertion sites. The available information strongly suggests that S. suis is an important antibiotic resistance reservoir that can contribute to the spread of resistance genes to the above-mentioned streptococci. S. suis is thus a paradigmatic example of possible intersections between animal and human resistomes.
Full Text Available Lorenzo Aguilar1, María-José Giménez1, José Barberán21Microbiology Department, School of Medicine, University Complutense, Madrid; 2Infectious Diseases Department, Hospital Central de la Defensa Gomez Ulla, Madrid, SpainAbstract: The nasopharynx is the ecological niche where evolution towards resistance occurs in respiratory tract isolates. Dynamics of different bacterial populations in antibiotic-free multibacterial niches are the baseline that antibiotic treatments can alter by shifting the competitive balance in favor of resistant populations. For this reason, antibiotic resistance is increasingly being considered to be an ecological problem. Traditionally, resistance has implied the need for development of new antibiotics for which basic efficacy and safety data are required prior to licensing. Antibiotic development is mainly focused on demonstrating clinical efficacy and setting susceptibility breakpoints for efficacy prediction. However, additional information on pharmacodynamic data predicting absence of selection of resistance and of resistant subpopulations, and specific surveillance on resistance to core antibiotics (to detect emerging resistances and its link with antibiotic consumption in the community are valuable data in defining the role of a new antibiotic, not only from the perspective of its therapeutic potential but also from the ecologic perspective (countering resistances to core antibiotics in the community. The documented information on cefditoren gleaned from published studies in recent years is an example of the role for an emerging oral antibacterial facing current antibiotic resistance in community-acquired respiratory tract infections.Keywords: respiratory tract infection, antibiotic resistance, cefditoren, community
Essencialidade e assistência farmacêutica: considerações sobre o acesso a medicamentos mediante ações judiciais no Brasil Essential drugs and pharmaceutical care: reflection on the access to drugs through lawsuits in Brazil
João Maurício Brambati Sant'Ana
Full Text Available A garantia do direito à assistência farmacêutica no ordenamento jurídico brasileiro a partir da Constituição de 1988 deu vazão a um aumento das demandas judiciais para efetivação desse direito. Esse fenômeno vem sendo chamado de judicialização da assistência farmacêutica. Estudos sobre o tema têm revelado tanto deficiências no acesso dos usuários do Sistema Único de Saúde aos medicamentos das listas oficiais de assistência farmacêutica como dificuldades do sistema de justiça e do próprio procedimento judicial para lidar com a temática. Este artigo discute essas questões considerando o arcabouço conceitual que informa a política de medicamentos e a política de assistência farmacêutica brasileiras, sobretudo os conceitos de medicamentos essenciais e de alocação de recursos escassos.The guarantee of pharmaceutical care as a legal right established by the Brazilian federal constitution of 1988 led to an increase in lawsuits to put that right into practice. This phenomenon has been dubbed the judicialization of pharmaceutical care. Studies on this topic have revealed, on the one hand, deficiencies in the access of Unified Health Care (SUS users to drugs included in Ministry of Health pharmaceutical care lists, and, on the other hand, limitations of the legal system to deal with the situation. The present article addresses these issues in the context of the conceptual framework that supports the Brazilian drug policy and pharmaceutical care policy, especially the notions of essential drugs and allocation of scarce resources.
Risoluti, R; Materazzi, S; Gregori, A; Ripani, L
Near-infrared spectroscopy (NIRs) is spreading as the tool of choice for fast and non-destructive analysis and detection of different compounds in complex matrices. This paper investigated the feasibility of using near infrared (NIR) spectroscopy coupled to chemometrics calibration to detect new psychoactive substances in street samples. The capabilities of this approach in forensic chemistry were assessed in the determination of new molecules appeared in the illicit market and often claimed to contain "non-illegal" compounds, although exhibiting important psychoactive effects. The study focused on synthetic molecules belonging to the classes of synthetic cannabinoids and phenethylamines. The approach was validated comparing results with officials methods and has been successfully applied for "in site" determination of illicit drugs in confiscated real samples, in cooperation with the Scientific Investigation Department (Carabinieri-RIS) of Rome. The achieved results allow to consider NIR spectroscopy analysis followed by chemometrics as a fast, cost-effective and useful tool for the preliminary determination of new psychoactive substances in forensic science. Copyright © 2016 Elsevier B.V. All rights reserved.
Peralta, Robert L; Stewart, Breanna C; Steele, Jennifer L; Wagner, Fernando A
Male-female variations in health-behavior continue to be of national and international significance with men generally being more likely to be engaged in behaviors that enhance risk across an array of preventable diseases and injuries as well as premature deaths. The literature has identified non-medical use of prescription drugs (NMUPD) as a developing and particularly dangerous substance use behavior among college students. The literature has reported sex differences (male; female) in NMUPD but has yet to explain how gender-orientation (e.g., masculine, feminine) might impact NMUPD. The purpose of this study is to address this gap by examining the influence of gender-orientation on NMUPD. Using survey data collected during the 2013-2014 academic year from a convenience sample of college students at a mid-sized Midwestern university, we examine the association of gender-orientation with NMUPD (N=796). To do this, we separate masculine and feminine scales from the BEM Sex Role Inventory and use logistic regression to test whether masculine or feminine gender characteristics influence the likelihood of NMUPD (lifetime measure of any use and by category). This analysis shows that self-identified characteristics associated with masculinity increase the odds of NMUPD while femininity is associated with lower odds of NMUPD. Findings from this study increase our knowledge of gender-orientation and sex interactions as factors that might influence NMUPD thus demonstrating the importance of differentiating sex from gender-orientation.
Full Text Available Intercommunication of Dopamine Receptors (DRs with their associate protein partners is crucial to maintain regular brain function in human. Majority of the brain disorders arise due to malfunctioning of such communication process. Hence, contributions of genetic factors, as well as phenotypic indications for various neurological and psychiatric disorders are often attributed as sharing in nature. In our earlier research article entitled “Human Dopamine Receptors Interaction Network (DRIN: a systems biology perspective on topology, stability and functionality of the network” (Podder et al., 2014 , we had depicted a holistic interaction map of human Dopamine Receptors. Given emphasis on the topological parameters, we had characterized the functionality along with the vulnerable properties of the network. In support of this, we hereby provide an additional data highlighting the genetic overlapping of various brain disorders in the network. The data indicates the sharing nature of disease genes for various neurological and psychiatric disorders in dopamine receptors connecting protein-protein interactions network. The data also indicates toward an alternative approach to prioritize proteins for overlapping brain disorders as valuable drug targets in the network.
Full Text Available Molecular-targeted therapy has been developed for cancer chemoprevention and treatment. Cancer cells have different metabolic properties from normal cells. Normal cells mostly rely upon the process of mitochondrial oxidative phosphorylation to produce energy whereas cancer cells have developed an altered metabolism that allows them to sustain higher proliferation rates. Cancer cells could predominantly produce energy by glycolysis even in the presence of oxygen. This alternative metabolic characteristic is known as the “Warburg Effect.” Although the exact mechanisms underlying the Warburg effect are unclear, recent progress indicates that glycolytic pathway of cancer cells could be a critical target for drug discovery. With a long history in cancer treatment, traditional Chinese medicine (TCM is recognized as a valuable source for seeking bioactive anticancer compounds. A great progress has been made to identify active compounds from herbal medicine targeting on glycolysis for cancer treatment. Herein, we provide an overall picture of the current understanding of the molecular targets in the cancer glycolytic pathway and reviewed active compounds from Chinese herbal medicine with the potentials to inhibit the metabolic targets for cancer treatment. Combination of TCM with conventional therapies will provide an attractive strategy for improving clinical outcome in cancer treatment.
Zawilska, Jolanta B; Wojcieszak, Jakub
Salvia divinorum is a sage endemic to a small region of Mexico and has been traditionally used by the Mazatec Indians for divination and spiritual healing. Recently, it has gained increased popularity as a recreational drug, used by adolescents and young adults as an alternative to marijuana and LSD. Salvinorin A, the major active ingredient of the plant, is considered to be the most potent known hallucinogen of natural origin. This review surveys the current state of knowledge on the neurochemical, pharmacokinetic, and pharmacological properties of salvinorin A, the trends and motivation behind S. divinorum use, and the health problems among users of the plant's products. S. divinorum induces intense, but short-lived, psychedelic-like changes in mood and perception, with concomitant hallucinations and disorientation. Many websites have misinterpreted the limited existing research-based information on the side effects of salvia as evidence for its safety. However, data accumulated over the last few years indicate that potential health risks are associated with the use of S. divinorum, especially by teenagers, users of other substances of abuse, and individuals with underlying psychotic disturbances. Taken together, the data presented in this review point to the need for further basic and clinical studies to create a basis for the development of well-addressed prevention and treatment strategies. Copyright © 2013 John Wiley & Sons, Ltd.
Khan, Haroon; Saeedi, Mina; Nabavi, Seyed Mohammad; Mubarak, Mohammad S; Bishayee, Anupam
Cancer continues to be a global burden, despite the advancement of various technological and pharmaceutical improvements over the past two decades. Methods for treating cancer include surgery, radiotherapy and chemotherapy in addition to other specialized techniques. On the other hand, medicinal plants have been traditionally employed either as the complementary medicine or dietary agents in the treatment and management of cancer. Medicinal plants are a rich source of secondary metabolites with interesting biological and pharmacological activities. Among these metabolites, glycosides are naturally occurring substances and have outstanding therapeutic potential and clinical utility. Different medical research engines such GoogleScholar, PubMed, SpringerLink, ScienceDirect were used to collect related literature on the subject matter. In this regard, only peer reviewed journals were considered. Emerging results showed that numerous glycosides isolated from various plants possessed marked anticancer activity against a variety of cancer cell lines. Accordingly, the aim of the present review is to shed light on the anticancer effects of glycosides, analyze possible mechanisms of action, and highlight the role of these natural agents as complementary and alternative medicine in combating and managing cancer. The glycosides isolated from different plants demonstrated potent cytotoxic effects against various cancer cell lines in initial preclinical studies. The anticancer effect was mediated through multiple mechanisms; however further detail studies are needed to understand the full potential of glycosides for clinical utility. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Margaret E. Mattson
Full Text Available Case reports in medical literature suggest that the atypical antipsychotic quetiapine, a medication not previously considered to have abuse potential, is now being subject to misuse and abuse (MUA; ie, taken when not prescribed for them or used in a way other than instructed by their health professional. Here we present systematic, nationally representative data from the 2005 to 2011 Drug Abuse Warning Network (DAWN for prevalence of emergency department (ED visits among the U.S. general population involving quetiapine and related to MUA, suicide attempts, and adverse reactions. Nationally, quetiapine-related ED visits increased 90% between 2005 and 2011, from 35,581 ED visits to 67,497. DAWN data indicate that when used without medical supervision for recreational/self-medication purposes, quetiapine poses health risks for its users, especially among polydrug users and women. These findings suggest that the medical and public health communities should increase vigilance concerning this drug and its potential for MUA.
Shah, Siddharth P; Patel, Kinner M; Subedi, Rogin; Gambhir, Harvir Singh
Oseltamivir is a very commonly prescribed anti-viral medication by the Emergency Medicine (EM) physicians for the prophylactic and therapeutic treatment of Influenza infection. While the drug interaction of Warfarin with various antibiotics is known, the drug interaction between Oseltamivir and Warfarin is not common. We present a case where an 83-year female patient, on Warfarin for Pulmonary Embolism, had worsening of coagulopathy after she was started on Oseltamivir. The INR was monitored daily in our patient and Warfarin was stopped when the INR became supra-therapeutic. Our patient did not have any minor or major bleeding complication. This is the first reported case of Oseltamivir related worsening coagulopathy in patient on Warfarin to the best of our knowledge. Keeping in mind the possible interaction between the two as it was evident in our case and few other published reports, we recommend monitoring the INR closely in patients using Warfarin after they are started on Oseltamivir therapy. Copyright © 2017 Elsevier Inc. All rights reserved.
Utku, Semih; Özcanhan, Mehmet Hilal; Unluturk, Mehmet Suleyman
Patient delivery time is no longer considered as the only critical factor, in ambulatory services. Presently, five clinical performance indicators are used to decide patient satisfaction. Unfortunately, the emergency ambulance services in rapidly growing metropolitan areas do not meet current satisfaction expectations; because of human errors in the management of the objects onboard the ambulances. But, human involvement in the information management of emergency interventions can be reduced by electronic tracking of personnel, assets, consumables and drugs (PACD) carried in the ambulances. Electronic tracking needs the support of automation software, which should be integrated to the overall hospital information system. Our work presents a complete solution based on a centralized database supported by radio frequency identification (RFID) and bluetooth low energy (BLE) identification and tracking technologies. Each object in an ambulance is identified and tracked by the best suited technology. The automated identification and tracking reduces manual paper documentation and frees the personnel to better focus on medical activities. The presence and amounts of the PACD are automatically monitored, warning about their depletion, non-presence or maintenance dates. The computerized two way hospital-ambulance communication link provides information sharing and instantaneous feedback for better and faster diagnosis decisions. A fully implemented system is presented, with detailed hardware and software descriptions. The benefits and the clinical outcomes of the proposed system are discussed, which lead to improved personnel efficiency and more effective interventions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Wang, Xin; Deng, Qi; Liu, Bin; Yu, Xiangdi
Using sevoflurane for pediatric anesthesia plays a pivotal role in surgeries. Emergence agitation (EA) is a major adverse event accompanied with pediatric anesthesia. Other anesthetic adjuvants can be combined with sevoflurane in clinical practices for different purposes. However, it is uncertain that such a practice may have substantial influence on the risk of EA. We conducted a literature search in online databases, including PubMed, Embase, Cochrane Library, and Clinical Trials. Key data were extracted from eligible randomized control trials (RCTs). Both pairwise and network meta-analysis (NMA) were conducted for synthesizing data from eligible studies. The relative risk of EA was assessed using the odds ratios (ORs) and their corresponding 95 % confidence intervals (CI) or credible intervals (CrI). Ranking scheme based on the surface under the cumulative ranking curve (SUCRA) values was produced. Several key assumptions of NMA such as heterogeneity, degree of consistence, and publication bias were validated by different statistical or graphical approaches. Evidence from 67 randomized control trials was synthesized. The relative risk of EA associated with eight anesthetic adjuvants was analyzed, including ketamine, propofol, dexmedetomidine, clonidine, midazolam, fentanyl, remifentanil, and sufentanil. Patients with the following anesthetic adjuvants appeared to have significantly reduced risk of EA in relation to those with placebo: dexmedetomidine (OR = 0.18, 95 % CrI 0.12-0.25), fentanyl (OR = 0.19, 95 % CrI 0.12-0.30), sufentanil (OR = 0.20, 95 % CrI 0.08-0.50), ketamine (OR = 0.21, 95 % CrI 0.13-0.34), clonidine (OR = 0.25, 95 % CrI 0.14-0.46), propofol (OR = 0.32, 95 % CrI 0.18-0.56), midazolam (OR = 0.46, 95 % CrI 0.27-0.77), and remifentanil (OR = 0.29, 95 % CrI 0.13-0.68). The SUCRA values for each anesthetic adjuvant were: dexmedetomidine (73.65 %), fentanyl (68.04 %), sufentanil (60.81 %), ketamine (59.99 %), clonidine
Gupta, Anamika; Pal, Sudhir K; Pandey, Divya; Fakir, Najneen A; Rathod, Sunita; Sinha, Dhiraj; SivaKumar, S; Sinha, Pallavi; Periera, Mycal; Balgam, Shilpa; Sekar, Gomathi; UmaDevi, K R; Anupurba, Shampa; Nema, Vijay
The Mycobacterium tuberculosis (M.tb) protein kinase B (PknB) which is now proved to be essential for the growth and survival of M.tb, is a transmembrane protein with a potential to be a good drug target. However it is not known if this target remains conserved in otherwise resistant isolates from clinical origin. The present study describes the conservation analysis of sequences covering the inhibitor binding domain of PknB to assess if it remains conserved in susceptible and resistant clinical strains of mycobacteria picked from three different geographical areas of India. A total of 116 isolates from North, South and West India were used in the study with a variable profile of their susceptibilities towards streptomycin, isoniazid, rifampicin, ethambutol and ofloxacin. Isolates were also spoligotyped in order to find if the conservation pattern of pknB gene remain consistent or differ with different spoligotypes. The impact of variation as found in the study was analyzed using Molecular dynamics simulations. The sequencing results with 115/116 isolates revealed the conserved nature of pknB sequences irrespective of their susceptibility status and spoligotypes. The only variation found was in one strains wherein pnkB sequence had G to A mutation at 664 position translating into a change of amino acid, Valine to Isoleucine. After analyzing the impact of this sequence variation using Molecular dynamics simulations, it was observed that the variation is causing no significant change in protein structure or the inhibitor binding. Hence, the study endorses that PknB is an ideal target for drug development and there is no pre-existing or induced resistance with respect to the sequences involved in inhibitor binding. Also if the mutation that we are reporting for the first time is found again in subsequent work, it should be checked with phenotypic profile before drawing the conclusion that it would affect the activity in any way. Bioinformatics analysis in our study
Leung, Ngai-Hang Z; Chen, Ana; Yadav, Prashant; Gallien, Jérémie
To characterize the impact of widespread inventory management policies on stock-outs of essential drugs in Zambia's health clinics and develop related recommendations. Daily clinic storeroom stock levels of artemether-lumefantrine (AL) products in 2009-2010 were captured in 145 facilities through photography and manual transcription of paper forms, then used to determine historical stock-out levels and estimate demand patterns. Delivery lead-times and estimates of monthly facility accessibility were obtained through worker surveys. A simulation model was constructed and validated for predictive accuracy against historical stock-outs, then used to evaluate various changes potentially affecting product availability. While almost no stock-outs of AL products were observed during Q4 2009 consistent with primary analysis, up to 30% of surveyed facilities stocked out of some AL product during Q1 2010 despite ample inventory being simultaneously available at the national warehouse. Simulation experiments closely reproduced these results and linked them to the use of average past monthly issues and failure to capture lead-time variability in current inventory control policies. Several inventory policy enhancements currently recommended by USAID | DELIVER were found to have limited impact on product availability. Inventory control policies widely recommended and used for distributing medicines in sub-Saharan Africa directly account for a substantial fraction of stock-outs observed in common situations involving demand seasonality and facility access interruptions. Developing central capabilities in peripheral demand forecasting and inventory control is critical. More rigorous independent peer-reviewed research on pharmaceutical supply chain management in low-income countries is needed.
Narbey, D; Jolly, D; Mahmoudi, R; Trenque, T; Blanchard, F; Novella, J-L; Dramé, M
To investigate the relationship between anticholinergic drug use and one-year outcome of elderly patients hospitalised via the emergency department. Prospective, multicentre, cohort study of patients aged 75 years and older. Comprehensive geriatric evaluation was performed. We included in this analysis all patients for whom data on drug use was available. Anticholinergic drugs were coded using the online database "Thesorimed". One-year mortality and nursing home admission were analysed using a Cox model, with matching on the propensity to use anticholinergic drugs. In total, 1176 subjects were included in this analysis, average age 85±6 years, 65% women. Overall, 144 (12%) were taking at least one anticholinergic drug. Mortality and nursing home admission at one year were respectively 29% and 30% in the anticholinergic group, and 34% and 33% respectively in subjects not taking anticholinergic drugs. No significant relationship was observed between anticholinergic drug use and the main endpoints. Although we did not observed any statistically significant relationship between use of anticholinergic drugs and one-year outcome in elderly patients, the long-term use of anticholinergic drugs can have deleterious effects on memory and functional capacity, and therefore requires prescriptions to be reviewed regularly.
Blow, Frederic C; Walton, Maureen A; Bohnert, Amy S B; Ignacio, Rosalinda V; Chermack, Stephen; Cunningham, Rebecca M; Booth, Brenda M; Ilgen, Mark; Barry, Kristen L
To examine efficacy of drug brief interventions (BIs) among adults presenting to a low-income urban emergency department (ED). Randomized controlled trial on drug use outcomes at 3, 6 and 12 months. Participants were assigned to (1) computer-delivered BI (Computer BI), (2) therapist-delivered, computer-guided BI (Therapist BI) or (3) enhanced usual care (EUC-ED) for drug-using adults. Participants were re-randomized after the 3-month assessment to either adapted motivational enhancement therapy (AMET) booster or enhanced usual care booster (EUC-B). Patients recruited from low-income urban emergency departments (ED) in Flint, Michigan, USA. A total of 780 ED patients reporting recent drug use, 44% males, mean age = 31 years. Computer BI consisted of an interactive program guided by a virtual health counselor. Therapist BI included computer guidance. The EUC-ED conditions included review of community health and HIV prevention resources. The BIs and boosters were based on motivational interviewing, focusing on reduction of drug use and HIV risk behaviors. Primary outcome was past 90 days using drugs at 6 and 12 months and secondary outcomes were weighted drug-days and days of marijuana use. Percentage changes in mean days used any drug from baseline to 12 months were: Computer BI + EUC-B: -10.9%, P = 0.0844; Therapist BI + EUC-B: -26.7%, P = 0.0041, for EUC-ED + EUC-B: -20.9, P = 0.0011. In adjusted analyses, there was no significant interaction between ED intervention and booster AMET for primary and secondary outcomes. Compared with EUC-ED, Therapist BI reduced number of days using any drug [95% confidence interval (CI) = -0.41, -0.07, P = 0.0422] and weighted drug-days (95% CI = -0.41, -0.08, P = 0.0283). Both Therapist and Computer BI had significantly fewer number of days using marijuana compared to EUC-ED (Therapist BI: 95% CI = -0.42, -0.06, P = 0.0104, Computer BI: 95% CI = -0.34, -0.01, P = 0.0406). Booster effects were not
J.P. van Geertruyden (Jean Pierre); J. Menten (Joris); R. Colebunders (Robert); E.L. Korenromp (Eline); U. D'Alessandro (Umberto)
textabstractBackground. HIV-related immune-suppression increases the risk of malaria (infection, disease and treatment failure) and probably the circulating parasite biomass, favoring the emergence of drug resistance parasites. Methods. The additional malaria parasite biomass related to HIV-1
Substance Abuse and Mental Health Services Administration, 2011
In 2008, adolescents made 23,124 visits to the emergency department (ED) for drug-related suicide attempts, and young adults made 38,036 such visits; of these visits, 23.0 percent (5,312 visits) among adolescents and 17.6 percent (6,700 visits) among young adults involved antidepressants. Among ED visits for suicide attempts involving…
Full Text Available The present study emphasizes on synthesis of bimetallic silver–gold nanoparticles from cell free supernatant of Pseudomonas veronii strain AS41G inhabiting Annona squamosa L. The synthesized nanoparticles were characterized using hyphenated techniques with UV–Visible spectra ascertained absorbance peak between 400 and 800 nm. Possible interaction of biomolecules in mediating and stabilization of nanoparticles was depicted with Fourier transform infrared spectroscopy (FTIR. X-ray diffraction (XRD displayed Bragg’s peak conferring the 100, 111, 200, and 220 facets of the face centered cubic symmetry of nanoparticles suggesting that these nanoparticles were crystalline in nature. Size and shape of the nanoparticles were determined using Transmission electron microscopy (TEM microgram with size ranging from 5 to 50 nm forming myriad shapes. Antibacterial activity of nanoparticles against significant human pathogens was conferred with well diffusion assay and its synergistic effect with standard antibiotics revealed 87.5% fold increased activity with antibiotic “bacitracin” against bacitracin resistant strains Bacillus subtilis, Escherichia coli and Klebsiella pneumoniae followed by kanamycin with 18.5%, gentamicin with 11.15%, streptomycin with 10%, erythromycin with 9.7% and chloramphenicol with 9.4%. Thus the study concludes with biogenic and ecofriendly route for synthesizing nanoparticles with antibacterial activity against drug resistant pathogens and attributes growing interest on endophytes as an emerging source for synthesis of nanoparticles.
KNIME Essentials is a practical guide aimed at getting the results you want, as quickly as possible.""Knime Essentials"" is written for data analysts looking to quickly get up to speed using the market leader in data processing tools, KNIME. No knowledge of KNIME is required, but we will assume that you have some background in data processing.
Full Text Available Objetivo. Determinar la asociación entre apoyo familiar (AF y apego al tratamiento de la hipertensión arterial esencial (HAS. Material y métodos. Estudio de casos y controles al que se integraron 80 sujetos con diagnóstico establecido de HAS, con 40 pacientes en cada grupo. Se consideró como casos a los pacientes con apego y como controles a los pacientes sin apego al tratamiento. El estudio se realizó de mayo a diciembre de 1999, en el Hospital Regional del IMSS, en la ciudad de Durango, Durango, México. La edad, género, duración de la HAS, escolaridad y estado civil fueron criterios de pareamiento. Las diferencias se establecieron con las pruebas ji cuadrada y t de student. Se calculó la razón de momios para estimar la fuerza de asociación. El diagnóstico de hipertensión arterial secundaria, o de otras enfermedades crónicas fueron criterios de exclusión. Resultados. No hubo diferencias entre los grupos respecto a las variables sociodemográficas, modalidad de tratamiento ni conocimiento que el enfermo tenía sobre su enfermedad. Tenían control de la presión arterial 31 (77.5% pacientes con apego y 11 (27.5% sin apego, p= 0.003. El AF se asoció de manera independiente con apego al tratamiento, RM 6.9, IC 95% 2.3-21.1. Conclusiones. El apego se vincula de forma significativa con el apoyo que los familiares otorgan al enfermo. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.htmlObjective. To assess the relationship between family support and drug therapy compliance in essential hypertension. Material and methods. A case-control study was conducted between May and December 1999, at Mexican Institute of Social Security Regional Hospital in Durango, among 80 hypertensive subjects; 40 were cases and 40 controls. Cases were subjects who complied with drug therapy and controls were those who did not, matched by age, gender, schooling, hypertensive disease duration, and marital status
Colin, Sophie; Chinetti-Gbaguidi, Giulia; Kuivenhoven, Jan A; Staels, Bart
Dyslipidaemia is a major risk factor for cardiovascular diseases. Pharmacological lowering of LDL-C levels using statins reduces cardiovascular risk. However, a substantial residual risk persists especially in patients with type 2 diabetes mellitus. Because of the inverse association observed in
Brass, Charles O
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Astronomy includes the historical perspective of astronomy, sky basics and the celestial coordinate systems, a model and the origin of the solar system, the sun, the planets, Kepler'
Combined effect of the essential oil from Chenopodium ambrosioides and antileishmanial drugs on promastigotes of Leishmania amazonensis Efeito combinado do óleo de essência de Chenopodium ambrosioides e drogas anti-leishmaniose nos promastigotas de Leishmania amazonensis
Lianet Monzote; Ana Margarita Montalvo; Ramón Scull; Migdalia Miranda; Juan Abreu
To date, there are no vaccines against Leishmania, and chemotherapy remains the mainstay for the control of leishmaniasis. The drugs of choice used for leishmaniasis therapy are significantly toxic, expensive and with a growing frequency of refractory infections. Because of these limitations, a combination therapy is the better hope. This work demonstrates that the essential oil from Chenopodium ambrosioides shows a synergic activity after incubation in conjunction with pentamidine against pr...
Barratt, Monica J; Lenton, Simon; Maddox, Alexia; Allen, Matthew
Cryptomarkets are digital platforms that use anonymising software (e.g. Tor) and cryptocurrencies (e.g. Bitcoin) to facilitate peer-to-peer (P2P) trade of goods and services. Their emergence has facilitated access to a wide range of high-quality psychoactive substances, according to surveys of users. In this paper, we ask the question 'How does changing access to drugs through cryptomarkets affect the drug use and harm trajectories of their users?' We conducted a digital ethnography spanning 2012-2014, a period that included the seizure of the original Silk Road marketplace and forum by law enforcement. Using encrypted online chat, we interviewed 17 people who reported using Silk Road to purchase illicit drugs. The interviews were in-depth and unstructured, and also involved the use of life history timelines to trace trajectories. Transcripts were analysed thematically using NVivo. For some, Silk Road facilitated initiation into drug use or a return to drug use after cessation. Typically, participants reported experiencing a glut of drug consumption in their first months using Silk Road, described by one participant as akin to 'kids in a candy store'. There was evidence that very high availability reduced the need for drug hoarding which helped some respondents to moderate use and feel more in control of purchases made online. Cryptomarket access also appeared to affect solitary and social drug users differently. Most participants described using other cryptomarkets after the closure of Silk Road, albeit with less confidence. In the context of high levels of drug access, supply and diversity occurring within a community regulated environment online, the impacts of cryptomarkets upon drug use trajectories are complex, often posing new challenges for self-control, yet not always leading to harmful outcomes. A major policy challenge is how to provide support for harm reduction in these highly volatile settings. Copyright © 2016 Elsevier B.V. All rights reserved.
Full Text Available Background. Essential thrombocythemia (ET is a chronic myeloproliferative disease with a platelet count within the range of 400–2000 × 109/L. Higher percentage of platelets in the circulation of patients with ET express also activation markers on their membranes. Two of such markers are P-selectin and activated fibrinogen on platelet membranes. Because of frequent thrombembolic and also bleeding related complications, treatment of ET is mandatory. Patients whose platelet count is less than 1000 × 109/L and who did not suffer any thrombembolic complication during the course of the disease, are ussually treated with an antiaggregation drug, acetylsalicylic acid 100 mg/daily orally. Clopidogrel is an adenosyn-di-phosphate (ADP receptor antagonist in platelets. There is no routine clinical data about clopidogrel treatment in the patients with ET and only sporadic case reports can be find in the literature.Patients and methods. In our clinical study we compared antiaggregational effects of acetylsalicylic acid and clopidogrel, by measuring the P-selectin level and activated fibrinogen expression on platelet membranes.There were 35 ET patients included, within the age range between 21 and 78 years and with platelet counts within 451–952 × 109/L. None of the patients did suffer any thrombembolic complication during the course of the disease. During the sequential 14 day periods, patients received acetylsalicylic acid 100 mg/daily orally, followed by clopidogrel 75 mg/daily orally and ultimativelly, together acetylsalicylic acid 100 mg/daily orally plus clopidogrel 75 mg/daily orally. After each fourteen days period the level of P-selectin and activated fibrinogen activated platelets were determined with monoclonal antibodies on flow cytometer. Statistical evaluation was calculated on the difference of average values between the two small, independent pair groups with the t-test.Results. When the patients stopped with acetylsalicylic acid and
Chomel, B B; Marano, N
A fundamental role of the veterinary profession is the protection of human health through wholesome food and control of diseases of animal origin, especially zoonoses. Therefore, training of veterinary students worldwide needs to face the new challenges posed by emerging infections, both from wildlife and domestic animals, as well as risks from bio/agroterrorism. New courses emphasising recognition, response, recovery and prevention must be developed to respond to natural or intentionally induced emerging diseases and zoonoses. Training programmes in applied epidemiology, zoonoses and foreign animal diseases are crucial for the development of a strong workforce to deal with microbial threats. Students should learn the reporting pathways for reportable diseases in their countries or states. Knowledge of the principles of ecology and ecosystems should be acquired during pre-veterinary studies. Elective classes on wildlife diseases, emphasising wildlife zoonotic diseases, should be offered during the veterinary curriculum, as well as a course on risk communication, since veterinarians are frequently in the position of having to convey complex information under adverse circumstances.
Shepherd, Marvin D
Existing federal law requires that a 72-hour emergency supply of a prescription drug be dispensed to Medicaid patients when prior authorization (PA) is not available and the medication is needed without delay. The pharmacist's role is to contact prescribers and inform them that PA is needed. If the prescriber cannot be reached, the pharmacist can dispense a 72-hour emergency supply. To determine (a) the reasons why some community pharmacy owners/managers, staff pharmacists, and technicians are not compliant with the law; (b) how often the decision is made; and (c) estimate how often pharmacies do not dispense the 72-hour emergency supply when PA is not available. A questionnaire was mailed to selected Texas community pharmacies. The instrument was developed by the researcher and reviewed by the Texas Medicaid Vendor Drug Program staff. The University of Texas, Office of Survey Research collected the data in September and October of 2011 by mail and online. The data were forwarded to the researcher for analyses. A total of 788 identified community pharmacies were mailed a packet containing 3 questionnaires to be completed by the pharmacist-in-charge, a staff pharmacist, and a pharmacy technician. There were 2 mailings of the questionnaire packet and follow-up telephone calls to nonrespondents. A total of 653 questionnaires were completed and returned from 288 community pharmacies (36.7%) out of 788 pharmacies that were mailed the questionnaire packets. A total of 368 (57.5%) completed questionnaires came from chain store pharmacy respondents and 272 (42.5%) questionnaires from independent pharmacy respondents. A total of 21.3% (n = 134) of the respondents indicated that they were not aware of the federal and state requirement to dispense a 72-hour emergency supply of a prescription drug to Medicaid patients when prior authorization (PA) is not available. A greater proportion of the chain store respondents (26.6%) were unaware of the requirement compared with the
Gorbunova, S.A.; Akhverdyan, V.Z.; Krylov, V.N.
The presence of a large number of clones, which have lost the ability to produce phase, is a feature of PpGl exconjugants, which have acquired markers of the hybrid plasmid containing the genome of the PAO1 phage transposon. Analysis of these clones indicates that they contain plasmids with different defects in the phage genome (point mutations and different deletion lengths which may have an effect on both the phage genome and also plasmid RP4). Mutations of a particular region are selected, the region of early prophage genes. The process of zygotic induction is an essential condition for the arisal of mutants (including deletion mutants). The results of the experiment, which was based on the Luria-Delbruik test, showed that a significant proportion of the mutations, including deletion mutations, arise in the recipient cells PpGl.
De Fraine, Bruno; Ernst, Erik; Südholt, Mario
Aspect-oriented programming (AOP) has produced interesting language designs, but also ad hoc semantics that needs clarification. We contribute to this clarification with a calculus that models essential AOP, both simpler and more general than existing formalizations. In AOP, advice may intercept...
Whether you are a seasoned Objective-C developer or new to the Xcode platform, Swift Essentials will provide you with all you need to know to get started with the language. Prior experience with iOS development is not necessary, but will be helpful to get the most out of the book.
Chow, Wei Zhen; Takebe, Yutaka; Syafina, Nur Ezreen; Prakasa, Malarvelli Soorya; Chan, Kok Gan; Al-Darraji, Haider Abdulrazzaq Abed; Koh, Clayton; Kamarulzaman, Adeeba; Tee, Kok Keng
The HIV epidemic is primarily characterised by the circulation of HIV-1 group M (main) comprising of 11 subtypes and sub-subtypes (A1, A2, B-D, F1, F2, G, H, J, and K) and to date 55 circulating recombinant forms (CRFs). In Southeast Asia, active inter-subtype recombination involving three main circulating genotypes--subtype B (including subtype B', the Thai variant of subtype B), CRF01_AE, and CRF33_01B--have contributed to the emergence of novel unique recombinant forms. In the present study, we conducted the molecular epidemiological surveillance of HIV-1 gag-RT genes among 258 people who inject drugs (PWIDs) in Kuala Lumpur, Malaysia, between 2009 and 2011 whereby a novel CRF candidate was recently identified. The near full-length genome sequences obtained from six epidemiologically unlinked individuals showed identical mosaic structures consisting of subtype B' and CRF01_AE, with six unique recombination breakpoints in the gag-RT, pol, and env regions. Among the high-risk population of PWIDs in Malaysia, which was predominantly infected by CRF33_01B (>70%), CRF58_01B circulated at a low but significant prevalence (2.3%, 6/258). Interestingly, the CRF58_01B shared two unique recombination breakpoints with other established CRFs in the region: CRF33_01B, CRF48_01B, and CRF53_01B in the gag gene, and CRF15_01B (from Thailand) in the env gene. Extended Bayesian Markov chain Monte Carlo sampling analysis showed that CRF58_01B and other recently discovered CRFs were most likely to have originated in Malaysia, and that the recent spread of recombinant lineages in the country had little influence from neighbouring countries. The isolation, genetic characterization, and evolutionary features of CRF58_01B among PWIDs in Malaysia signify the increasingly complex HIV-1 diversity in Southeast Asia that may hold an implication on disease treatment, control, and prevention.
Wei Zhen Chow
Full Text Available The HIV epidemic is primarily characterised by the circulation of HIV-1 group M (main comprising of 11 subtypes and sub-subtypes (A1, A2, B-D, F1, F2, G, H, J, and K and to date 55 circulating recombinant forms (CRFs. In Southeast Asia, active inter-subtype recombination involving three main circulating genotypes--subtype B (including subtype B', the Thai variant of subtype B, CRF01_AE, and CRF33_01B--have contributed to the emergence of novel unique recombinant forms. In the present study, we conducted the molecular epidemiological surveillance of HIV-1 gag-RT genes among 258 people who inject drugs (PWIDs in Kuala Lumpur, Malaysia, between 2009 and 2011 whereby a novel CRF candidate was recently identified. The near full-length genome sequences obtained from six epidemiologically unlinked individuals showed identical mosaic structures consisting of subtype B' and CRF01_AE, with six unique recombination breakpoints in the gag-RT, pol, and env regions. Among the high-risk population of PWIDs in Malaysia, which was predominantly infected by CRF33_01B (>70%, CRF58_01B circulated at a low but significant prevalence (2.3%, 6/258. Interestingly, the CRF58_01B shared two unique recombination breakpoints with other established CRFs in the region: CRF33_01B, CRF48_01B, and CRF53_01B in the gag gene, and CRF15_01B (from Thailand in the env gene. Extended Bayesian Markov chain Monte Carlo sampling analysis showed that CRF58_01B and other recently discovered CRFs were most likely to have originated in Malaysia, and that the recent spread of recombinant lineages in the country had little influence from neighbouring countries. The isolation, genetic characterization, and evolutionary features of CRF58_01B among PWIDs in Malaysia signify the increasingly complex HIV-1 diversity in Southeast Asia that may hold an implication on disease treatment, control, and prevention.
Bonar, Erin E; Walton, Maureen A; Cunningham, Rebecca M; Chermack, Stephen T; Bohnert, Amy S B; Barry, Kristen L; Booth, Brenda M; Blow, Frederic C
This article describes process data from a randomized controlled trial among 781 adults recruited in the emergency department who reported recent drug use and were randomized to: intervener-delivered brief intervention (IBI) assisted by computer, computerized BI (CBI), or enhanced usual care (EUC). Analyses examined differences between baseline and post-intervention on psychological constructs theoretically related to changes in drug use and HIV risk: importance, readiness, intention, help-seeking, and confidence. Compared to EUC, participants receiving the IBI significantly increased in confidence and intentions; CBI patients increased importance, readiness, confidence, and help-seeking. Both groups increased relative to the EUC in likelihood of condom use with regular partners. Examining BI components suggested that benefits of change and tools for change were associated with changes in psychological constructs. Delivering BIs targeting drug use and HIV risk using computers appears promising for implementation in healthcare settings. This trial is ongoing and future work will report behavioral outcomes. © 2013.
Full Text Available Despite evidence from high income countries, it is not known whether screening and brief interventions (SBI for alcohol and other drug (AOD use are feasible to implement in low and middle income countries. This paper describes the feasibility and acceptability of a peer-led SBI for AOD-using patients presenting with injuries at emergency services in Cape Town, South Africa. Data were extracted from program records on the number of eligible patients screened and the number of program refusals. A questionnaire examined preliminary responses to the intervention for 30 patients who had completed the program and 10 emergency personnel. Peer counselors were also interviewed to identify barriers to implementation. Of the 1458 patients screened, 21% (305 met inclusion criteria, of which 74% (225 were enrolled in the intervention. Of the 30 patients interviewed, most (83% found the program useful. Emergency personnel were supportive of the program but felt that visibility and reach could improve. Peer counselors identified the need for better integration of the program into emergency services and for additional training and support. In conclusion, with limited additional resources, peer-led SBIs for AOD use are feasible to conduct in South African emergency services and are acceptable to patients and emergency personnel.
Iwasa, Megumi; Iwasaki, Toshiki; Ono, Toshirou; Miyazawa, Mitsuo
The chemical composition of the essential oil from PINELLIA TUBER (Japanese name: Hange), the dried rhizome of Pinellia ternata, was investigated by capillary gas chromatography (GC) and GC-mass spectrometry (MS) analyses. The oil obtained from Pinellia tuber was revealed the presence of 114 compounds, representing 90.6% of the total oil identified. This colorless oil had a spicy and woody odor. The main components of the oil were β-cubebene (8.8%), atractylon (7.8%), methyl eugenol (6.2%), and δ-cadinene (5.3%). Fifteen major odor-active compounds were identified in the essential oil from PINELLIA TUBER by the GC-olfactometry (GC-O) and aroma extract dilution analysis (AEDA). Among these, safrole (spicy) and β-vatirenene (woody) showed the highest flavor dilution (FD) factor (128), followed by paeonol (FD = 64; woody, spicy), α-humulene (FD = 64; woody), and β-phenylnaphthalene (FD = 64; spicy).
Understanding communication between emergency and consulting physicians: a qualitative study that describes and defines the essential elements of the emergency department consultation-referral process for the junior learner.
Chan, Teresa; Orlich, Donika; Kulasegaram, Kulamakan; Sherbino, Jonathan
To define the important elements of an emergency department (ED) consultation request and to develop a simple model of the process. From March to September 2010, 61 physicians (21 emergency medicine [EM], 20 general surgery [GS], 20 internal medicine [IM]; 31 residents, 30 attending staff) were questioned about how junior learners should be taught about ED consultation. Two investigators independently reviewed focus group and interview transcripts using grounded theory to generate an index of themes until saturation was reached. Disagreements were resolved by consensus, yielding an inventory of themes and subthemes. All transcripts were coded using this index of themes; 30% of transcripts were coded in duplicate to determine the agreement. A total of 245 themes and subthemes were identified. The agreement between reviewers was 77%. Important themes in the process were as follows: initial preparation and review of investigations by EM physician (overall endorsement 87% [range 70-100% in different groups]); identification of involved parties (patient and involved physicians) (100%); hypothesis of patient's diagnosis (75% [range 62-83%]) or question for the consulting physician (70% [range 55-95%]); urgency (100%) and stability (74% [range 62-80%]); questions from the consultant (100%); discussion/communication (98% [range 95-100%]); and feedback (98% [range 95-100%]). These components were reorganized into a simple framework (PIQUED). Each clinical specialty significantly contributed to the model (χ2 = 7.9; p value = 0.019). Each group contributed uniquely to the final list of important elements (percent contributions: EM, 57%; GS, 41%; IM, 64%). We define important elements of an ED consultation with input from emergency and consulting physicians. We propose a model that organizes these elements into a simple framework (PIQUED) that may be valuable for junior learners.
Liu, Hanqing; Tu, Zhigang; Feng, Fan; Shi, Haifeng; Chen, Keping; Xu, Ximing
A virosome is an innovative hybrid drug delivery system with advantages of both viral and non-viral vectors. Studies have shown that a virosome can carry various biologically active molecules, such as nucleic acids, peptides, proteins and small organic molecules. Targeted drug delivery using virosome-based systems can be achieved through surface modifications of virosomes. A number of virosome-based prophylactic and therapeutic products with high safety profiles are currently available in the market. Cancer treatment is a big battlefield for virosome-based drug delivery systems. This review provides an overview of the general concept, preparation procedures, working mechanisms, preclinical studies and clinical applications of virosomes in cancer treatment.
Full Text Available Asthma is a chronic, reversible obstructive disease that when in exacerbation can present to the emergency department in a spectrum of severity. Prompt recognition of the potentially severely ill asthmatic requires a careful history and physical exam while considering alternative diagnoses for the presenting symptoms. Early administration of salbutamol and corticosteroids is indicated in almost all patients with other medications such as ipratropium and magnesium and supportive modalities like BiPAP reserved for sicker patients. The global impact of asthma is increasing, especially amongst children. While the benign clinical presentation is most common and mortality has decreased in recent decades due to improved recognition and care, the ubiquity of the condition and frequent lack of regular outpatient management contribute to the disease claiming 250,000 lives worldwide annually. The emergency physician must be prepared to assess and appropriately manage both the young child with a mild wheeze and the adult in respiratory failure.
The CTD2 Center at Emory University has developed a computational methodology to combine high-throughput knockdown data with known protein network topologies to infer the importance of protein-protein interactions (PPIs) for the survival of cancer cells. Applying these data to the Achilles shRNA results, the CCLE cell line characterizations, and known and newly identified PPIs provides novel insights for potential new drug targets for cancer therapies and identifies important PPI hubs.
Chetan S. Urade
Full Text Available Objectives- To study the prescription pattern of antihypertensive drugs and analyze the medication adherence to antihypertensive drugs at rural tertiary care teaching hospital.Materials and Methods- Prospective, observational, 12 weeks, questionnaire based study, conducted in rural tertiary care teaching hospital of central India. 214 antihypertensive prescriptions were analyzed by Morisky medication adherence scale. Statistical analysis was done by MS Excel and Graph pad prism 6.0.Results- 28.03% patients were not aware about the medicines taken, 29.90% patients were unacquainted about dose and route of administration whereas 32.71% patients were unfamiliar about frequency of administration of medicines. 53.27% patients were unaware about precautions to be taken while consuming medicines. 58.68% & 12.67% patients consumed amlodipine & atenolol respectively. In 16.43% patients, atenolol + amlodipine combination therapy was prescribed. Amongst 214 patients 12, 58 & 144 showed high, medium & low adherence respectively. No significant difference was found on gender basis at any level of adherence.Conclusion- In this study, physicians given preference to amlodipine than other antihypertensive drugs. However, thiazide is a first line drug in stage 1 hypertension, recommended by JNC VII guideline. This indicates that there is need of creating awareness about current management of hypertension to clinicians by organizing various workshops. We observed only 5.60% patients showed high adherence to antihypertensive therapy. Therefore educational strategies must be carried out for physicians focusing on causes for nonadherence to antihypertensive medications. Also raising patient trust in their physicians may improve patient motivation to prescribed medication.
Smith, Roderick W
A unique, full-color introduction to Linux fundamentals Serving as a low-cost, secure alternative to expensive operating systems, Linux is a UNIX-based, open source operating system. Full-color and concise, this beginner's guide takes a learning-by-doing approach to understanding the essentials of Linux. Each chapter begins by clearly identifying what you will learn in the chapter, followed by a straightforward discussion of concepts that leads you right into hands-on tutorials. Chapters conclude with additional exercises and review questions, allowing you to reinforce and measure your underst
Essential SQLAlchemy introduces a high-level open-source code library that makes it easier for Python programmers to access relational databases such as Oracle, DB2, MySQL, PostgreSQL, and SQLite. SQLAlchemy has become increasingly popular since its release, but it still lacks good offline documentation. This practical book fills the gap, and because a developer wrote it, you get an objective look at SQLAlchemy's tools rather than an advocate's description of all the "cool" features. SQLAlchemy includes both a database server-independent SQL expression language and an object-relational mappe
If you want to learn Prezi, and specifically design within Prezi, this is the book for you. Perhaps you already know a bit about Prezi but have never used it, or perhaps you have used Prezi before but want to learn how to incorporate your own custom design elements. In either case, this book will get you up and running quickly. It would be helpful to have a bit of familiarity with basic design concepts and the use of Prezi, but prior experience is not essential.
Zaidi, Syed Mohammad Asad; Haseeb, Abdul; Habib, Shifa Salman; Malik, Amyn; Khowaja, Saira; SaifUllah, Nausheen; Rizvi, Nadeem
Pakistan is classified as one of the high multi-drug resistant tuberculosis (MDR-TB) burden countries. A poorly regulated private sector, over-prescription of antibiotics and self-medication has led to augmented rates of drug-resistance in the country. Pakistan's first national anti-tuberculosis drug resistance survey identified high prevalence of fluoroquinolone resistance among MDR-TB patients. Further institutional evidence of fluoroquinolone drug-resistance can support re-evaluation of treatment regimens as well as invigorate efforts to control antibiotic resistance in the country. In this study, data for drug-susceptibility testing (DST) was retrospectively analyzed for a total of 133 patients receiving MDR-TB treatment at the Chest Department of Jinnah Postgraduate Medical Center, Karachi, Pakistan. Frequency analyses for resistance patterns was carried out and association of fluoroquinolone (ofloxacin) resistance with demographics and past TB treatment category were assessed. Within first-line drugs, resistance to isoniazid was detected in 97.7% of cases, followed by rifampicin (96.9%), pyrazinamide (86.4%), ethambutol (69.2%) and streptomycin (64.6%). Within second-line drugs, ofloxacin resistance was detected in 34.6% of cases. Resistance to ethionamide and amikacin was 2.3% and 1.6%, respectively. Combined resistance of oflaxacin and isoniazid was detected in 33.9% of cases. Age, gender and past TB treatment category were not significantly associated with resistance to ofloxacin. Fluoroquinolone resistance was observed in an alarmingly high proportion of MDR-TB cases. Our results suggest caution in their use for empirical management of MDR-TB cases and recommended treatment regimens for MDR-TB may require re-evaluation. Greater engagement of private providers and stringent pharmacy regulations are urgently required.
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Jensen, Mette; Groth, L.; Holmer, G.
were fed with a fat-free diet lacking linoleic acid. The EFAD condition was established within 8 weeks. In order to ensure that this condition had been established, several parameters were measured and observed, i.e. animal weight, water consumption, transepidermal water loss, clinical skin symptoms...... with calcipotriol. Dithranol and its coal tar-containing vehicle also showed a reductive effect on epidermal thickness. EFAD hairless rats possess various histological changes resembling psoriasis. These histological changes normalise during treatment with anti-psoriatic drugs as calcipotriol, dithranol and coal...
Lang, Kenneth R
Essential Astrophysics is a book to learn or teach from, as well as a fundamental reference volume for anyone interested in astronomy and astrophysics. It presents astrophysics from basic principles without requiring any previous study of astronomy or astrophysics. It serves as a comprehensive introductory text, which takes the student through the field of astrophysics in lecture-sized chapters of basic physical principles applied to the cosmos. This one-semester overview will be enjoyed by undergraduate students with an interest in the physical sciences, such as astronomy, chemistry, engineering or physics, as well as by any curious student interested in learning about our celestial science. The mathematics required for understanding the text is on the level of simple algebra, for that is all that is needed to describe the fundamental principles. The text is of sufficient breadth and depth to prepare the interested student for more advanced specialized courses in the future. Astronomical examples are provide...
Full Text Available Background and Objective: Pain is an emotional and unpleasant experience associated with actual or potential tissue damage. The literature shows no study on the effect of aromatherapy with the essential oil of orange on unpleasant feelings of patients with fractured limbs. In this regard, this paper aims at studying the effect of aromatherapy with the essential oil of orange on patients with fractured limbs admitted to the emergency ward. Methods: Sixty patients admitted to the emergency ward of Vali-e-Asr Hospital were selected by purposive sampling method and then were divided into two groups of control and experiment by block method. This study was done in one shift work (morning or afternoon. Four drops of the orange oil were poured on a pad and were pinned with a plastic pin to the patient's collar, about 20 cm distant from head. The old pad was replaced by the new one every 1 h. The patients' pain and vital signs were checked every 1 h for at last 6 h. The data were analyzed by SPSS Version 21. Results: Forty (66.7% patients were male and twenty (33.3% were female. Their age average was 37.93 ± 18.19 years old. The most fractured cases were in the scapular (11 patients [18.3%]. Friedman test showed that pain in the experiment group (P = 0.0001 decreased significantly rather than the control group (0.339. However, in vital signs, there could be found that no significant change between the two groups was seen. Conclusion: Aromatherapy with orange oil can relieve pain in patients with fractured limbs but has no effect on their vital signs. Therefore, aromatherapy with orange oil can be used as a complementary medicine in these patients.
Scully, Christopher G; Forrest, Shawn; Galeotti, Loriano; Schwartz, Suzanne B; Strauss, David G
The Food and Drug Administration (FDA) performs regulatory science to provide science-based medical product regulatory decisions. This article describes the types of scientific research the FDA's Center for Devices and Radiological Health performs and highlights specific projects related to medical devices for emergency medicine. In addition, this article discusses how results from regulatory science are used by the FDA to support the regulatory process as well as how the results are communicated to the public. Regulatory science supports the FDA's mission to assure safe, effective, and high-quality medical products are available to patients. Published by Elsevier Inc.
McGillivray, Jane A.; McCabe, Marita P.
Background: Concerns about the pharmacological management of the behaviour of individuals with intellectual disability have resulted in the development of legislative and procedural controls. Method: This Australian study provided a comparison of 873 reported cases where drugs were administered to manage behaviour in March 2000, with 762 cases…
Raschi, Emanuel; De Ponti, Fabrizio
Drug-induced liver injury (DILI) and herb-induced liver injury is a hot topic for clinicians, academia, drug companies and regulators, as shown by the steadily increasing number of publications in the past 15 years. This review will first provide clues for clinicians to suspect idiosyncratic (unpredictable) DILI and succeed in diagnosis. Causality assessment remains challenging and requires careful medical history as well as awareness of multifaceted aspects, especially for herbs. Drug discontinuation and therapy reconciliation remain the mainstay in patent's management to minimize occurrence of acute liver failure. The second section will address novel agents associated with liver injury in 2014 (referred to as "signals"), especially in terms of clinical, research and drug development implications. Insights will be provided into recent trends by highlighting the contribution of different post-marketing data, especially registries and spontaneous reporting systems. This literature scrutiny suggests: (1) the importance of post-marketing databases as tools of clinical evidence to detect signals of DILI risk; and (2) the need for joining efforts in improving predictivity of pre-clinical assays, continuing post-marketing surveillance and design ad hoc post-authorization safety studies. In this context, ongoing European/United States research consortia and novel pharmaco-epidemiological tools (e.g., specialist prescription event monitoring) will support innovation in this field. Direct oral anticoagulants and herbal/dietary supplements appear as key research priorities.
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Full Text Available Sustained virological response (SVR rates have increased dramatically following the approval of direct acting antiviral (DAA therapies. While individual DAAs have a low barrier to resistance, most patients can be successfully treated using DAA combination therapy. However, DAAs are vulnerable to drug resistance, and resistance-associated variants (RAVs may occur naturally prior to DAA therapy or may emerge following drug exposure. While most RAVs are quickly lost in the absence of DAAs, compensatory mutations may reinforce fitness. However, the presence of RAVs does not necessarily preclude successful treatment. Although developments in hepatitis C virus (HCV therapy in Asia have largely paralleled those in the United States, Japan’s July 2014 approval of asunaprevir plus daclatasvir combination therapy as the first all-oral interferon-free therapy was not repeated in the United States. Instead, two different combination therapies were approved: sofosbuvir/ledipasvir and paritaprevir/ritonavir/ombitasvir/dasabuvir. This divergence in treatment approaches may lead to differences in resistance challenges faced by Japan and the US. However, the recent approval of sofosbuvir plus ledipasvir in Japan and the recent submissions of petitions for approval of paritaprevir/ritonavir plus ombitasvir suggest a trend towards a new consensus on emerging DAA regimens.
Gundersen, Oystein Hoel; Mordal, Jon; Berman, Anne H; Bramness, Jørgen G
High rates of substance use disorders (SUD) among psychiatric patients are well documented. This study explores the usefulness of the Alcohol Use Disorders Identification Test (AUDIT) and the Drug Use Disorders Identification Test (DUDIT) in identifying SUD in emergency psychiatric patients. Of 287 patients admitted consecutively, 256 participants (89%) were included, and 61-64% completed the questionnaires and the Mini-International Neuropsychiatric Interview (MINI), used as the reference standard. Both AUDIT and DUDIT were valid (area under the curve above 0.92) and reliable (Cronbach's alpha above 0.89) in psychotic and nonpsychotic men and women. The suitable cutoff scores for AUDIT were higher among the psychotic than nonpsychotic patients, with 12 versus 10 in men and 8 versus 5 in women. The suitable cutoff scores for DUDIT were 1 in both psychotic and nonpsychotic women, and 5 versus 1 in psychotic and nonpsychotic men, respectively. This study shows that AUDIT and DUDIT may provide precise information about emergency psychiatric patients' problematic alcohol and drug use. Copyright © 2013 S. Karger AG, Basel.
Thevis, Mario; Schänzer, Wilhelm
The number and diversity of potentially performance-enhancing substances is continuously growing, fueled by new pharmaceutical developments but also by the inventiveness and, at the same time, unscrupulousness of black-market (designer) drug producers and providers. In terms of sports drug testing, this situation necessitates reactive as well as proactive research and expansion of the analytical armamentarium to ensure timely, adequate, and comprehensive doping controls. This review summarizes literature published over the past 5 years on new drug entities, discontinued therapeutics, and 'tailored' compounds classified as doping agents according to the regulations of the World Anti-Doping Agency, with particular attention to analytical strategies enabling their detection in human blood or urine. Among these compounds, low- and high-molecular mass substances of peptidic (e.g. modified insulin-like growth factor-1, TB-500, hematide/peginesatide, growth hormone releasing peptides, AOD-9604, etc.) and non-peptidic (selective androgen receptor modulators, hypoxia-inducible factor stabilizers, siRNA, S-107 and ARM036/aladorian, etc.) as well as inorganic (cobalt) nature are considered and discussed in terms of specific requirements originating from physicochemical properties, concentration levels, metabolism, and their amenability for chromatographic-mass spectrometric or alternative detection methods. Copyright © 2014 Elsevier B.V. All rights reserved.
Birdi, K S
Surface chemistry plays an important role in everyday life, as the basis for many phenomena as well as technological applications. Common examples range from soap bubbles, foam, and raindrops to cosmetics, paint, adhesives, and pharmaceuticals. Additional areas that rely on surface chemistry include modern nanotechnology, medical diagnostics, and drug delivery. There is extensive literature on this subject, but most chemistry books only devote one or two chapters to it. Surface Chemistry Essentials fills a need for a reference that brings together the fundamental aspects of surface chemistry w
Full Text Available BACKGROUND: Certain non-steroidal anti-inflammatory drugs (NSAIDs (e.g., rofecoxib [Vioxx] increase the risk of heart attack and stroke and should be avoided in patients at high risk of cardiovascular events. Rates of cardiovascular disease are high and rising in many low- and middle-income countries. We studied the extent to which evidence on cardiovascular risk with NSAIDs has translated into guidance and sales in 15 countries. METHODS AND FINDINGS: Data on the relative risk (RR of cardiovascular events with individual NSAIDs were derived from meta-analyses of randomised trials and controlled observational studies. Listing of individual NSAIDs on Essential Medicines Lists (EMLs was obtained from the World Health Organization. NSAID sales or prescription data for 15 low-, middle-, and high-income countries were obtained from Intercontinental Medical Statistics Health (IMS Health or national prescription pricing audit (in the case of England and Canada. Three drugs (rofecoxib, diclofenac, etoricoxib ranked consistently highest in terms of cardiovascular risk compared with nonuse. Naproxen was associated with a low risk. Diclofenac was listed on 74 national EMLs, naproxen on just 27. Rofecoxib use was not documented in any country. Diclofenac and etoricoxib accounted for one-third of total NSAID usage across the 15 countries (median 33.2%, range 14.7-58.7%. This proportion did not vary between low- and high-income countries. Diclofenac was by far the most commonly used NSAID, with a market share close to that of the next three most popular drugs combined. Naproxen had an average market share of less than 10%. CONCLUSIONS: Listing of NSAIDs on national EMLs should take account of cardiovascular risk, with preference given to low risk drugs. Diclofenac has a risk very similar to rofecoxib, which was withdrawn from worldwide markets owing to cardiovascular toxicity. Diclofenac should be removed from EMLs.
Schneider Kristan A
Full Text Available Abstract Background Considering the distinct biological characteristics of Plasmodium species is crucial for control and elimination efforts, in particular when facing the spread of drug resistance. Whereas the evolutionary fitness of all malarial species could be approximated by the probability of being taken by a mosquito and then infecting a new host, the actual steps in the malaria life cycle leading to a successful transmission event show differences among Plasmodium species. These “steps” are called fitness components. Differences in terms of fitness components may affect how selection imposed by interventions, e.g. drug treatments, differentially acts on each Plasmodium species. Thus, a successful malaria control or elimination programme should understand how differences in fitness components among different malaria species could affect adaptive evolution (e.g. the emergence of drug resistance. In this investigation, the interactions between some fitness components and natural selection are explored. Methods A population-genetic model is formulated that qualitatively explains how different fitness components (in particular gametocytogenesis and longevity of gametocytes affect selection acting on merozoites during the erythrocytic cycle. By comparing Plasmodium falciparum and Plasmodium vivax, the interplay of parasitaemia and gametocytaemia dynamics in determining fitness is modelled under circumstances that allow contrasting solely the differences between these two parasites in terms of their fitness components. Results By simulating fitness components, it is shown that selection acting on merozoites (e.g., on drug resistant mutations or malaria antigens is more efficient in P. falciparum than in P. vivax. These results could explain, at least in part, why resistance against drugs, such as chloroquine (CQ is highly prevalent in P. falciparum worldwide, while CQ is still a successful treatment for P. vivax despite its massive use
Full Text Available Two distinct classes of methicillin-resistant Staphylococcus aureus (MRSA are spreading in hospitals (as hospital-acquired MRSA, HA-MRSA and in the community (as community-acquired MRSA, CA-MRSA. Multilocus sequence type (ST 239 MRSA, one of the most worldwide-disseminated lineages, has been noted as a representative HA-MRSA. Here, we isolated ST239 MRSA (spa type 3 [t037] and staphylococcal cassette chromosome mec [SCCmec] type III.1.1.1 and its novel variant with ST239/spa351 (t030/SCCmecIII.1.1.4 (SCCmecIII(R not only from hospitals but also from patients with urethritis in the community in Russia. The Russian variant (strain 16K possessed a hybrid genome consisting of CC8 and CC30, similar to the ST239/spa3/SCCmecIII.1.1.1 HA-MRSA (TW20 genome, but with marked diversity. The 16K' CC30 section had SCCmecIII(R carrying the dcs-carrying unit (which corresponded to the SCCmecIVc J3 joining region of ST30 CA-MRSA, lacked SCCmercury, and possessed a novel mobile element structure (MES16K carrying the ccrC-carrying unit (with the recombinase gene ccrC1 allele 3 and drug resistance tranposons. The Russian variant included strains with a high ability to transfer its multiple drug resistance by conjugation; e.g., for strain 16K, the transfer frequency of a chloramphenicol resistance plasmid (p16K-1 with 2.9 kb in size reached 1.4×10(-2, followed by Tn554 conjugative transfer at 3.6×l0(-4. The Russian variant, which has been increasing recently, included divergent strains with different plasmid patterns and pulsed field gel electrophoresis profiles. The data demonstrate the alternative nature of ST239 MRSA as CA-MRSA and also as a drug resistance disseminator, and its micro but dynamic evolution in Russia.
Disponibilidad de medicamentos esenciales en unidades de primer nivel de la Secretaría de Salud de Tamaulipas, México Availability of essential drugs in Ministry of Health first level healthcare units in Tamaulipas, Mexico
medicamentos en el país, en general, y la disponibilidad de medicamentos esenciales en las unidades de primer nivel, en particular. Dos iniciativas de reciente puesta en marcha permiten ser optimistas al respecto: la descentralización de los servicios de salud para población no asegurada y el Programa de Medicamentos Genéricos Intercambiables, implantado en el ámbito nacional en 1998.OBJECTIVE: To describe the availability of some essential drugs at the primary health care units of the Ministry of Health of Tamaulipas, Mexico. MATERIAL AND METHODS: Between September and October 1998, all first level healthcare units of Tamaulipas' three sanitary jurisdictions were surveyed. Drug availability was assessed. The measurement instrument was a checklist of 56 drugs and 10 different supplies. For each drug and input the absolute number and the proportion of units with this drug or input was calculated. In the units where the drugs were available, the medians were calculated. The median of the total number of drugs available in all units was used as a global indicator. This same exercise was developed for each unit. Comparisons between the availability of these inputs in the units and stockrooms were also done. Stata 5.0 was used for statistical analysis. RESULTS: None of the inspected units had full availability of all checklist drugs. The highest percentage of drug availability was 84% and the lowest was 32%. There was limited availability of antibiotics, antihypertensive, hypoglycemic, and iron deficiency drugs. The availability of oral rehydration salts and contraceptive and vaccine agents was acceptable. CONCLUSIONS: Healthcare organizations must find alternative ways to improve access to drugs nationwide, in general, and availability of essential drugs in first level healthcare units, in particular. Two recent initiatives provide an optimistic outlook: decentralization of health services for the uninsured and the Generic Exchangeable Drugs Program, established nationwide in
Hickman, R.; Anspaugh, L.
FEMA has broad roles in the management of disasters potentially involving substantial amounts of radioactive contamination. These could be either peacetime or wartime disasters. A meeting was held in March 1985 to see if there are any research contributions that FEMA might reasonably make in the area of radioprotective drugs that would substantially enhance its ability to perform its mission. The other federal agencies presently sponsoring research in the field were represented at the meeting. A few selected researchers also participated to provide complementary viewpoints. Activities of a modest scale that FEMA might undertake were identified, as were larger scale activities that might be undertaken in the event of long-term, major funding-level increases for FEMA. 2 refs
Full Text Available BACKGROUND: During 2011, a dramatic increase (1600% of reported HIV-1 infections among injecting drug users (IDUs was noted in Athens, Greece. We herein assess the potential causal pathways associated with this outbreak. METHODS: Our study employed high resolution HIV-1 phylogenetic and phylogeographic analyses. We examined also longitudinal data of ecological variables such as the annual growth of gross domestic product (GDP of Greece in association with HIV-1 and HCV sentinel prevalence in IDUs, unemployment and homelessness rates and HIV transmission networks in Athens IDUs before and during economic recession (2008-2012. RESULTS: IDU isolates sampled in 2011 and 2012 suggested transmission networks in 94.6% and 92.7% of the cases in striking contrast with the sporadic networking (5% during 1998-2009. The geographic origin of most HIV-1 isolates was consistent with the recently documented migratory waves in Greece. The decline in GDP was inversely correlated with annual prevalence rates of HIV and HCV and with unemployment and homelessness rates in IDUs (all p<0.001. The slope of anti-HCV prevalence in the sentinel populations of IDUs and in "new" drug injectors was found 120 and 1.9-fold (p = 0.007, p = 0.08 respectively higher in 2008-2012 (economic recession compared with 2002-2006. The median (25th, 75th size of transmission networks were 34 (12, 58 and 2 (2, 2 (p = 0.057 in 2008-2012 and 1998-2007, respectively. The coverage of harm reduction services was low throughout the study period. CONCLUSIONS: Scaling-up harm reduction services and addressing social and structural factors related to the current economic crisis should be urgently considered in environments where HIV-1 outbreaks may occur.
Zaurova, Milana; Hoffman, Robert S; Vlahov, David; Manini, Alex F
Synthetic cannabinoid receptor agonists (SCRAs) are heterogeneous compounds originally intended as probes of the endogenous cannabinoid system or as potential therapeutic agents. We assessed the clinical toxicity associated with recent SCRA use in a large cohort of drug overdose patients. This subgroup analysis of a large (n = 3739) drug overdose cohort study involved consecutive ED patients at two urban teaching hospitals collected between 2009 and 2013. Clinical characteristics of patients with the exposure to SCRAs (SRCA subgroup) were compared with those from patients who smoked traditional cannabinoids (marijuana subgroup). Data included demographics, exposure details, vital signs, mental status, and basic chemistries gathered as part of routine clinical care. Study outcomes included altered mental status and cardiotoxicity. Eighty-seven patients reported exposure to any cannabinoid, of whom 17 reported SCRAs (17 cases, 70 controls, mean age 38.9 years, 77 % males, 31 % Hispanic). There were no significant differences between SRCA and marijuana with respect to demographics (age, gender, and race/ethnicity), exposure history (suicidality, misuse, and intent), vital signs, or serum chemistries. Mental status varied between SRCA and marijuana, with agitation significantly more likely in SCRA subgroup (OR = 3.8, CI = 1.2-11.9). Cardiotoxicity was more pronounced in the SCRA subgroup with dysrhythmia significantly more likely (OR = 9.2, CI = 1.0-108). In the first clinical study comparing the adverse effects of SCRA overdose vs. marijuana controls in an ED population, we found that SCRA overdoses had significantly pronounced neurotoxicity and cardiotoxicity compared with marijuana.
Combined effect of the essential oil from Chenopodium ambrosioides and antileishmanial drugs on promastigotes of Leishmania amazonensis Efeito combinado do óleo de essência de Chenopodium ambrosioides e drogas anti-leishmaniose nos promastigotas de Leishmania amazonensis
Full Text Available To date, there are no vaccines against Leishmania, and chemotherapy remains the mainstay for the control of leishmaniasis. The drugs of choice used for leishmaniasis therapy are significantly toxic, expensive and with a growing frequency of refractory infections. Because of these limitations, a combination therapy is the better hope. This work demonstrates that the essential oil from Chenopodium ambrosioides shows a synergic activity after incubation in conjunction with pentamidine against promastigotes of Leishmania amazonensis. However, an indifferent effect has been found for combinations of meglumine antimoniate or amphotericin B and the essential oil.Até hoje não temos vacina contra a Leishmania e a quimioterapia é a indicação para o controle desta doença. Os remédios que hoje utilizamos são tóxicos e muito caros e além disso o resultado não é sempre o desejado. Por isso, uma terapia de combinação é a melhor opção. Este trabalho mostra que o óleo de essência de C. ambrosioides tem atividade sinérgica junto com a pentamidina sobre os promastigotas de L. amazonensis, diferente do resultado da combinação de antimônio de meglumine e anfotericina B e o óleo de essência.
Choo, Esther; Guthrie, K Morrow; Mello, Michael; Wetle, Terrie F; Ranney, Megan; Tapé, Chantal; Zlotnick, Caron
Addressing violence and linking women to community services in parallel with drug change goals is critical for women with coexisting intimate partner violence (IPV) and substance use disorders (SUD). Our objective was to develop a Web-based intervention to address violence and drug use among women patients in the ED. The intervention was developed in a five-step process: 1) Initial intervention development based on selected theoretical frameworks; 2) In-depth interviews with the target population; 3) Intervention adaptation, with iterative feedback from further interviews; 4) Beta testing and review by an advisory committee of domestic violence advocates; 5) Acceptability and feasibility testing in a small open trial. Themes supported the selection of MI and empowerment models but also guided major adaptations to the intervention, including the introduction of videos and a more robust booster phone call. Participants in the open trial reported high scores for satisfaction, usability, and consistency with essential elements of motivational interviewing. This qualitative work with our target population of women in the ED with SUD experiencing IPV underscored the importance of connection to peers and empathetic human contact. We developed an acceptable and feasible intervention distinct from prior ED-based brief interventions for substance-using populations.
A T Makadzange
Full Text Available To determine immunologic, virologic outcomes and drug resistance among children and adolescents receiving care during routine programmatic implementation in a low-income country.A cross-sectional evaluation with collection of clinical and laboratory data for children (0-<10 years and adolescents (10-19 years attending a public ART program in Harare providing care for pediatric patients since 2004, was conducted. Longitudinal data for each participant was obtained from the clinic based medical record.Data from 599 children and adolescents was evaluated. The participants presented to care with low CD4 cell count and CD4%, median baseline CD4% was lower in adolescents compared with children (11.0% vs. 15.0%, p<0.0001. The median age at ART initiation was 8.0 years (IQR 3.0, 12.0; median time on ART was 2.9 years (IQR 1.7, 4.5. On ART, median CD4% improved for all age groups but remained below 25%. Older age (≥ 5 years at ART initiation was associated with severe stunting (HAZ <-2: 53.3% vs. 28.4%, p<0.0001. Virologic failure rate was 30.6% and associated with age at ART initiation. In children, nevirapine based ART regimen was associated with a 3-fold increased risk of failure (AOR: 3.5; 95% CI: 1.3, 9.1, p = 0.0180. Children (<10 y on ART for ≥4 years had higher failure rates than those on ART for <4 years (39.6% vs. 23.9%, p = 0.0239. In those initiating ART as adolescents, each additional year in age above 10 years at the time of ART initiation (AOR 0.4 95%CI: 0.1, 0.9, p = 0.0324, and each additional year on ART (AOR 0.4, 95%CI 0.2, 0.9, p = 0.0379 were associated with decreased risk of virologic failure. Drug resistance was evident in 67.6% of sequenced virus isolates.During routine programmatic implementation of HIV care for children and adolescents, delayed age at ART initiation has long-term implications on immunologic recovery, growth and virologic outcomes.
Marwood, Joseph; Aguirrebarrena, Gonzalo; Kerr, Stephen; Welch, Susan A; Rimmer, Janet
Self-reported penicillin allergy is common among patients attending the ED, but is a poor predictor of true immunoglobulin E-mediated hypersensitivity to penicillin. We hypothesise that with a combination of skin testing and drug provocation testing, selected patients can be safely de-labelled of their allergy. This prospective study enrolled a sample of patients presenting to an urban academic ED between 2011 and 2016 with a self-reported allergy to penicillin. Standardised skin prick and intradermal testing with amoxicillin and both major and minor determinants of penicillin was performed in the department. If negative, testing was followed by a graded oral challenge of amoxicillin over 9 days. The primary end point was the allergy status of participants at the end of the study. A total of 100 patients (mean age 42; standard deviation 14 years; 54% women) completed the testing. Of these, 81% (95% confidence interval 71.9-88.2) showed no hypersensitivity to penicillin and were labelled non-allergic. The majority (16/19) of allergies were confirmed by skin testing, with three suspected allergies detected by the oral challenge. Women were more likely than men to have a true penicillin allergy, with odds ratio of 4.0 (95% confidence interval 1.23-13.2). There were no serious adverse events. Selected patients in the ED who self-report an allergy to penicillin can be safely tested there for penicillin allergy, using skin tests and oral drug provocation testing. This testing allows a significant de-labelling of penicillin allergy, with the majority of these patients able to tolerate penicillin without incident. © 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.
Paraskevis, Dimitrios; Nikolopoulos, Georgios; Fotiou, Anastasios; Tsiara, Chrissa; Paraskeva, Dimitra; Sypsa, Vana; Lazanas, Marios; Gargalianos, Panagiotis; Psichogiou, Mina; Skoutelis, Athanasios; Wiessing, Lucas; Friedman, Samuel R.; Jarlais, Don C. d. e. s.; Terzidou, Manina; Kremastinou, Jenny; Malliori, Meni; Hatzakis, Angelos
Background During 2011, a dramatic increase (1600%) of reported HIV-1 infections among injecting drug users (IDUs) was noted in Athens, Greece. We herein assess the potential causal pathways associated with this outbreak. Methods Our study employed high resolution HIV-1 phylogenetic and phylogeographic analyses. We examined also longitudinal data of ecological variables such as the annual growth of gross domestic product (GDP) of Greece in association with HIV-1 and HCV sentinel prevalence in IDUs, unemployment and homelessness rates and HIV transmission networks in Athens IDUs before and during economic recession (2008–2012). Results IDU isolates sampled in 2011 and 2012 suggested transmission networks in 94.6% and 92.7% of the cases in striking contrast with the sporadic networking (5%) during 1998–2009. The geographic origin of most HIV-1 isolates was consistent with the recently documented migratory waves in Greece. The decline in GDP was inversely correlated with annual prevalence rates of HIV and HCV and with unemployment and homelessness rates in IDUs (all pperiod. Conclusions Scaling-up harm reduction services and addressing social and structural factors related to the current economic crisis should be urgently considered in environments where HIV-1 outbreaks may occur. PMID:24265730
Al-Niemat, Sahar I.; Bloukh, Diana T.; Al-Harasis, Manal D.; Al-Fanek, Alen F.; Salah, Rehab K.
Objective was to evaluate the use of antibiotics prescribed in hospital outpatient and emergency clinics in King Hussein Medical Centre (KHMC) using WHO prescribing indicators in an attempt to rationalize the use of antibiotics in the Royal Medical Services. We retrospectively surveyed a sample of 187,822 antibiotic prescriptions obtained from 5 outpatient pharmacies in KHMC written over the period of 3 consecutive months May 2007 to July 2007. The percentage of encounters of an antibiotic prescribed was calculated using the methodology recommended by the WHO. An additional indicator, the percentage share of different antibiotics was also included to identify the frequency prescribed from those antibiotics. The average percentage of prescriptions involving antibiotics was 35.6% out of 187,822 prescriptions surveyed. From these, 65,500 antibiotic prescriptions were observed. Penicillins most frequently amoxcillins and Quinolones most frequently ciprofloxacinllin and norfloxacillin were the most commonly prescribed antibiotics with an average percentage of 31.8% and 27.5%. The average prescribing rate for the other antibiotic categories was as follows: macrolides 5.2%, cephalosporins 16% and amoxcillins/clavulanate 5.4%. The high percentage of prescriptions involving antibiotics observed in KHMC pharmacies requires rational use of antibiotics and judicious prescribing by Military prescribers. An insight into factors influencing antibiotic prescribing patterns and adherence to antibiotic prescribing guidelines by the Military prescribers is warranted. (author)
Tofilon, P.J.; Arundel, C.; Vines, C.M.
Repeated administration of antineoplastic chemotherapeutic agents is generally considered to induce and/or select for drug resistant cells. The authors recently begun to investigate whether chemotherapy interdigitated with radiation can minimize or eliminate the emergence of drug resiistent cells in 9L rat brain tumor spheroids grown from defined mixtures of cells sensitive (9L) and resistant (R/sub 3/) to BCNU. In this experimental system, the sister chromatid exchange (SCE) assay is used to quantitate the proportions of sensitive and resistant cells within the spheroids. While 9L and R/sub 3/ cell have different sensitivities to BCNU, they are equally sensitive to radiation. Mixed-cell spheroids consisting of 1% R/sub 3/ cells were treated with three doses of BCNU (10 μM) every 72 hr resulting in a shift in the 9L to R/sub 3/ ratio to greater than 50% R/sub 3/ cells. The combined protocols to be investigated will involve γ rays administered either 36 hr before or after each BCNU treatment. By initiating these combined protocols on spheroids of different sizes, the effectiveness of each protocol is evaluated with respect to the number of resistant cells present
van Dijk, D P; Dinant, G; Jacobs, J A
Drug donations to developing countries may be part of medical relief operations in acute emergencies, development aid in non-emergency situations, or a corporate donations programme. After a number of documented inappropriate drug donations, the World Health Organization developed the 'Guidelines for Drug Donations', with the second and final version published in 1999. We reviewed the medical literature on drug donations since the Guidelines publication in 1999. Literature was retrieved from PubMed and other on-line databases as well as from relevant websites providing medical literature for use in developing countries. We considered the following donations to be inappropriate: (i) essential drugs in excessive quantities; (ii) mixed unused drugs (unsorted medicines and free samples); and (iii) drug dumping (large quantities of useless medicines). We retrieved 25 publications dated after 1999, including 20 and 5 from the scientific literature and 'grey' literature (technical reports, working papers), respectively. New information concerned emergencies in East Timor, Mozambique, El Salvador, Gujarat State (India), Aceh (Indonesia) and Sri Lanka. Except for East Timor and Gujarat, inappropriate donations still occurred, accounting for 85%, 37%, 70% and 80% of donations in Mozambique, El Salvador, Aceh and Sri Lanka, respectively. Very little information was found on drug donations in non-emergency situations. There are few recent reports on the compliance of drug donations with the World Health Organization guidelines. For emergency situations, there is still room for improvement. Drug donations in non-emergency situations need to be evaluated. A reform of drug donations policy is needed.
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Hipertensão arterial sistêmica no setor de emergência: o uso de medicamentos sintomáticos como alternativa de tratamento Systemic hypertension at emergency units: the use of symptomatic drugs as choice for management
Sandro Gonçalves de Lima
íveis estabelecidos no critério de alta e tornaram-se assintomáticos após o período de observação.OBJECTIVE: Compare the therapeutic response of symptomatic, hypertensive patients to symptomatic medication or anti-hypertensive drugs at the Emergency Unit. METHODS: A randomized, blind clinical trial involving 100 (one hundred patients assisted at the Cardiology Emergency Unit at Oswaldo Cruz University Hospital (HUOC. All patients reported symptoms associated to systolic pressure (SBP between 180 and 200 mmHg and/or diastolic pressure (DBP between 110 and 120 mmHg. Patients were randomized for treatment with symptomatic (dipirone or diazepan or anti-hipertensive drug (captopril. Those reporting any associated clinical condition and in need of immediate treatment at the Emergency Unit were excluded from the study. Patients reporting no symptoms, and systolic pressure reduced to levels under 180 mmHg and diastolic pressure under 110 mmHg after the 90-minute period were considered as having met discharge criteria. RESULTS: Mean age of population studied was 54.4 years old, most commonly females. Patients were chronic hypertensive, on irregular pharmacological treatment, with low compliance to non-pharmacologic actions, and classified as overweight and obese grade I. Headache, type D (non-angina chest pain, and dyspnea were the most frequent complaints. The number of patients treated with symptomatic drug who reached discharge criteria was similar to that of patients treated with anti-hypertensive (p=0.165. No association was found between previous high blood pressure (HBP diagnosis (p=0.192, pharmacological treatment (p=0.687, and non-pharmacological treatment and discharge criteria. CONCLUSION: Blood pressure (BP was reduced below levels for discharge criteria for a (non-significant higher rate of patients treated with symptomatic drug, who were turned into asymptomatic after the observation period.
Suffoletto, Brian; Lynch, Michael; Pacella, Charissa B; Yealy, Donald M; Callaway, Clifton W
Prescription drug monitoring programs (PDMPs) enable registered prescribers to obtain real-time information on patients' prescription history of controlled medications. We sought to describe the effect of a state-mandated PDMP on opioid prescribing by emergency medicine providers. We retrospectively analyzed electronic medical records of 122,732 adult patients discharged with an opioid prescription from 15 emergency departments in a single health system in Pennsylvania from July 2015 to March, 2017. We used an interrupted time series design to evaluate the percentage of patients discharged each month with an opioid prescription before and after state law-mandated PDMP use on August 25, 2016. From August (pre-PDMP) to September, 2016 (post-PDMP), the opioid prescribing rate decreased from 12.4% (95% confidence interval [CI], 10.8%-14.1%) to 10.2% (95% CI, 8.8%-11.8%). For each month between September 2016 to March 2017, there was a mean decline of .46% (95% CI, -.38% to -.53%) in the percentage of patients discharged with an opioid prescription. There was heterogeneity in opioid prescribing across hospitals as well as according to patient diagnosis. This study examined the effect of a state-mandated PDMP on opioid prescribing among emergency medicine providers from 15 different hospitals in a single health system. Findings support current PDMP mandates in reducing opioid prescriptions, which could curb the prescription opioid epidemic and may ultimately reduce abuse, misuse, and overdose death. Copyright © 2017 The American Pain Society. Published by Elsevier Inc. All rights reserved.
Proyecto Grannacional ALBASALUD para Centro Regulador de Medicamentos Esenciales de los países del ALBA-TCP Grand-national Project ALBASALUD for Regulatory Center of Essential Drugs for the ALBA-TCP countries
Celeste Aurora Sánchez González
countries. It will provide a Grand-national Register that will be valid for all the member states to facilitate the access to quality essential drugs. The objective of this research work was to design and to conduct a project from the technical viewpoint in order to lay down the legal and methodological basis of the future center and its main functions. Some techniques like nominal group, points of reference and expert consultation were used, and the specific methodologies to plan and to prepare the required documents were devised. The guidelines of international regulatory bodies, the basic groups of drugs and the pharmaceutical regulations of the participating countries were reviewed. Several documents and strategies for the project work in the pre-investment stage were developed, the first listing of essential drugs for the ALBA countries was defined and the main legal provisions and the regulation that states the functions of registering, surveillance, supervision, lab work and release of batches of the new entity were approved. The Grand-national Project ALBASALUD " Regulatory Center of Drugs for the ALBA-TCP" has proved its efficiency and capacities to achieve the set objectives through collective involvement-supported scientific and technical work that has guaranteed the required provisions and guidelines for the basic functions and the legal endorsement of the center.
Bei, Chengli; Fu, Manjiao; Zhang, Yao; Xie, Hebin; Yin, Ke; Liu, Yanke; Zhang, Li; Xie, Bangruan; Li, Fang; Huang, Hua; Liu, Yuhong; Yang, Li; Zhou, Jing
Limited treatment options of extensive drug-resistant tuberculosis (XDR-TB) have led to its high mortality worldwide. Relevant data about mortality of XDR-TB patients in literature are limited and likely underestimate the real situation in China, since the majority of patients with XDR-TB are lost to follow-up after discharge from TB hospitals. In this study, we sought to investigate the mortality and associated risk factors of Human Immunodeficiency Virus (HIV)-negative patients with XDR-TB in China. All patients who were diagnosed with XDR-TB for the first time in four TB care centers across China between March 2013 and February 2015 were consecutively enrolled. Active tracking through contacting patients or family members by phone or home visit was conducted to obtain patients' survival information by February 2017. Multivariable Cox regression models were used to evaluate factors associated with mortality. Among 67 patients enrolled, the mean age was 48.7 (Standard Deviation [SD] = 16.7) years, and 51 (76%) were men. Fourteen patients (21%) were treatment naïve at diagnosis indicating primary transmission. 58 (86.8%) patients remained positive for sputum smear or culture when discharged. During a median follow-up period of 32 months, 20 deaths occurred, with an overall mortality of 128 per 1000 person-years. Among patients who were dead, the median survival was 5.4 months (interquartile range [IQR]: 2.2-17.8). Seventeen (85%) of them died at home, among whom the median interval from discharge to death was 8.4 months (IQR: 2.0-18.2). In Cox proportional hazards regression models, body mass index (BMI) study suggested an alarming situation of XDR-TB patients in China with a sizable proportion of newly transmitted cases, a high mortality rate, and a long period in community. This observation calls for urgent actions to improve XDR-TB case management in China, including providing regimens with high chances of cure and palliative care, and enhanced infection
This paper distinguishes between Jung's theoretical discourse regarding the archetypes and his phenomenological account of numinous experience. For this author, the initial attraction of 'my Jung' came from both the vivid Romanticism of his descriptions of the anima and the apparent 'ground of being' offered by his theory of archetypes. However, the essentialism inherent to archetypal theory in general and the anima in particular has necessitated a re-evaluation of Jung's theory in terms of emergence theory. My own version of this emphasises the role of symbols in the constitution of affect through collective human action in the world. In this reconfiguration, the visceral energy of numinous experience is retained while the problematic theory of archetypes is no longer needed. © 2018, The Society of Analytical Psychology.
Murti, Y V G S
Current literature on Nonlinear Optics varies widely in terms of content, style, and coverage of specific topics, relative emphasis of areas and the depth of treatment. While most of these books are excellent resources for the researchers, there is a strong need for books appropriate for presenting the subject at the undergraduate or postgraduate levels in Universities. The need for such a book to serve as a textbook at the level of the bachelors and masters courses was felt by the authors while teaching courses on nonlinear optics to students of both science and engineering during the past two decades. This book has emerged from an attempt to address the requirement of presenting the subject at college level. A one-semester course covering the essentials can effectively be designed based on this.
Liu, Huixin; Ma, Ye; Su, Yingying; Smith, M. Kumi; Liu, Ying; Jin, Yantao; Gu, Hongqiu; Wu, Jing; Zhu, Lin; Wang, Ning
Background. Highly active antiretroviral therapy (HAART) has led to a dramatic decrease in AIDS-related morbidity and mortality through sustained suppression of human immunodeficiency virus (HIV) replication and reconstitution of the immune response. Settings like China that experienced rapid HAART rollout and relatively limited drug selection face considerable challenges in controlling HIV drug resistance (DR). Methods. We conducted a systematic review and meta-analysis to describe trends in emergent HIV DR to first-line HAART among Chinese HIV-infected patients, as reflected in the point prevalence of HIV DR at key points and fixed intervals after treatment initiation, using data from cohort studies and cross-sectional studies respectively. Results. Pooled prevalence of HIV DR from longitudinal cohorts studies was 10.79% (95% confidence interval [CI], 5.85%–19.07%) after 12 months of HAART and 80.58% (95% CI, 76.6%–84.02%) after 72 months of HAART. The HIV DR prevalence from cross-sectional studies was measured in treatment intervals; during the 0–12-month HAART treatment interval, the pooled prevalence of HIV DR was 11.1% (95% CI, 7.49%–16.14%), which increased to 22.92% at 61–72 months (95% CI, 9.45%–45.86%). Stratified analyses showed that patients receiving a didanosine-based regimen had higher HIV DR prevalence than those not taking didanosine (15.82% vs 4.97%). Patients infected through former plasma donation and those receiving AIDS treatment at village clinics had higher HIV DR prevalence than those infected through sexual transmission or treated at a county-level hospital. Conclusions. Our findings indicate higher prevalence of HIV DR for patients with longer cumulative HAART exposure, highlighting important subgroups for future HIV DR surveillance and control. PMID:25053721
Hawk, Kathryn; D'Onofrio, Gail; Fiellin, David A; Chawarski, Marek C; O'Connor, Patrick G; Owens, Patricia H; Pantalon, Michael V; Bernstein, Steven L
Despite increasing reliance on prescription drug monitoring programs (PDMPs) as a response to the opioid epidemic, the relationship between aberrant drug-related behaviors captured by the PDMP and opioid use disorder is incompletely understood. How PDMP data should guide emergency department (ED) assessment has not been studied. The objective was to evaluate a relationship between PDMP opioid prescription records and self-reported nonmedical opioid use of prescription opioids in a cohort of opioid-dependent ED patients enrolled in a treatment trial. PDMP opioid prescription records during 1 year prior to study enrollment on 329 adults meeting Diagnostic and Statistical Manual IV criteria for opioid dependence entering a randomized clinical trial in a large, urban ED were cross-tabulated with data on 30-day nonmedical prescription opioid use self-report. The association among these two types of data was assessed by the Goodman and Kruskal's gamma; a logistic regression was used to explore characteristics of participants who had PDMP record of opioid prescriptions. During 1 year prior to study enrollment, 118 of 329 (36%) patients had at least one opioid prescription (range = 1-51) in our states' PDMP. Patients who reported ≥15 of 30 days of nonmedical prescription opioid use were more likely to have at least four PDMP opioid prescriptions (20/38; 53%) than patients reporting 1 to 14 days (14/38, 37%) or zero days of nonmedical prescription opioid use (4/38, 11%; p = 0.002). Female sex and having health insurance were significantly more represented in the PDMP (p Medicine.
Hong, Steven Y; Jonas, Anna; DeKlerk, Michael; Shiningavamwe, Andreas; Desta, Tiruneh; Badi, Alfons; Morris, Lynn; Hunt, Gillian M; Ledwaba, Johanna; Sheehan, Heidi B; Lau, Kiger; Trotter, Andrew; Tang, Alice M; Wanke, Christine; Jordan, Michael R
The World Health Organization (WHO) prospective surveys of acquired HIV drug resistance (HIVDR) evaluate HIVDR emerging after the first year of antiretroviral therapy (ART) and associated factors. Consecutive ART starters in 2009 were enrolled at 3 sentinel sites in Namibia. Genotyping was performed at start and after 12 months in patients with HIV viral load (VL) >1000 copies per mL. HIVDR outcomes were: HIVDR prevention (VL ≤1000 copies/mL), possible HIVDR (VL >1000 copies/mL without detectable HIVDR or loss to follow-up or ART stop), and HIVDR (VL >1000 copies/mL with detectable HIVDR). Adherence was assessed using medication possession ratio (MPR). Of 394 starters, at 12 months, 80% were on first-line ART, 1% died, 4% transferred out, 1% stopped ART, <1% switched to second-line, and 15% were lost to follow-up. Among patients on first-line, 77% had VL testing, and 94% achieved VL ≤1000 copies per mL. At baseline, 7% had HIVDR. After 12 months, among patients with VL testing, 5% had HIVDR. A majority of patients failing therapy had high-level resistance to nonnucleoside reverse transcriptase inhibitors but none to protease inhibitors. All sites achieved the WHO target of ≥70% HIVDR prevention. Factors associated with not achieving HIVDR prevention were: baseline resistance to nonnucleoside reverse transcriptase inhibitors [odds ratio (OR) 3.0, P = 0.023], WHO stage 3 or 4 at baseline (OR 2.0, P = 0.012), and MPR <75% (OR 4.9, P = 0.021). Earlier ART initiation and removal of barriers to on-time drug pickups may help to prevent HIVDR. These data inform decisions at national and global levels on the effectiveness of first- and second-line regimens.
Effects of oral glucose-lowering drugs on long term outcomes in patients with diabetes mellitus following myocardial infarction not treated with emergent percutaneous coronary intervention--a retrospective nationwide cohort study
Jørgensen, Casper H; Gislason, Gunnar H; Andersson, Charlotte
The optimum oral pharmacological treatment of diabetes mellitus to reduce cardiovascular disease and mortality following myocardial infarction has not been established. We therefore set out to investigate the association between individual oral glucose-lowering drugs and cardiovascular outcomes...... following myocardial infarction in patients with diabetes mellitus not treated with emergent percutaneous coronary intervention....
Cao, Yongzhong; Shen, Yongxiu; Cheng, Lingling; Zhang, Xiaorong; Wang, Chao; Wang, Yan; Zhou, Xiaohui; Chao, Guoxiang; Wu, Yantao
Salmonellae is one of the most important foodborne pathogens and becomes resistant to multiple antibiotics, which represents a significant challenge to food industry and public health. However, a molecular signature that can be used to distinguish antimicrobial resistance profile, particularly multi-drug resistance or extensive-drug resistance (XDR). In the current study, 168 isolates from the chicken and pork production chains and ill chickens were characterized by serotyping, antimicrobial susceptibility test, multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). The results showed that these isolates belonged to 13 serotypes, 14 multilocus sequence types (STs), 94 PFGE genotypes, and 70 antimicrobial resistant profiles. S. Enteritidis, S. Indiana, and S. Derby were the predominant serotypes, corresponding to the ST11, ST17, and ST40 clones, respectively and the PFGE Cluster A, Cluster E, and Cluster D, respectively. Among the ST11-S. Enteritidis (Cluster A) and the ST40-S. Derby (Cluster D) clones, the majority of isolates were resistant to 4-8 antimicrobial agents, whereas in the ST17S. Indiana (Cluster E) clone, isolates showed extensive-drug resistance (XDR) to 9-16 antimicrobial agents. The bla TEM-1-like gene was prevalent in the ST11 and ST17 clones corresponding to high ampicillin resistance. The bla TEM-1-like , bla CTX-M , bla OXA-1-like , sul1, aaC4, aac(6')-1b, dfrA17, and floR gene complex was highly prevalent among isolates of ST17, corresponding to an XDR phenotype. These results demonstrated the association of the resistant phenotypes and genotypes with ST clone and PFGE cluster. Our results also indicated that the newly identified gene complex comprising bla TEM-1-like , bla CTX-M , bla OXA-1-like , sul1, aaC4, aac(6')-1b, dfrA17, and floR, was responsible for the emergence of the ST17S. Indiana XDR clone. ST17 could be potentially used as a molecular signature to distinguish S. Indiana XDR clone. Copyright © 2017
Torres Bonafonte, Olga H; Gil Olivas, Eva; Pérez Macho, Estefanía; Pacho Pacho, Cristina; Mateo Roca, Miriam; Casademont Pou, Jordi; Ruiz Hidalgo, Domingo
To analyze factors related to drug-resistant pathogens (DRPs) in community-onset pneumonia (COP) and whether previously suggested criteria are useful in our emergency-department. Prospective 1-year study of adults coming to the emergency department for COP. We assessed the usefulness of criteria used in health-care-associated pneumonia (HCAP), as well the Shorr index, the Barthel index, and clinical suspicion of resistant pathogens. Data were analyzed by multiple logistic regression and the area under the receiver operating characteristic curve (AUC). We included 139 patients with a mean (SD) age of 75.9 (15.3) years; 63.3% were men. Forty-nine COP patients (35.2%) were at risk for DRP-caused pneumonia according to HCAP criteria; 43 (30.9%) according to the Shorr index, and 56 (40.3%) according to the Aliberti index. A score of less than 60 derived from the Barthel index was recorded for 25 patients (18%). Clinical suspicion of a DRP was recorded for 11 (7.9%). A DRP was isolated in 5 patients (3.6%) (3, Pseudomonas aeruginosa; 2, methicillin-resistant Staphylococcus aureus). Multiple logistic regression analysis identified 2 predictors of DRP-caused COP: hospital admission within the last 90 days (odds ratio [OR], 8.92; 95% CI, 1.92-41.45) and initial arterial blood oxygen saturation (OR, 0.85; 95% CI, 0.74-0.98). The AUC was 0.91 (95% CI, 0.85-0.98). The model identified 22 patients (16.8%) at risk for DRP-caused pneumonia. The positive and negative predictive values were 20% and 99.1%, respectively, for the model 90-day period (vs 8.7% and 98.9%, respectively, for criteria used in HCAP). Hospitalization within the 90-day period before a COP emergency and arterial blood oxygen saturation were good predictors of DRP in our setting. Criteria of DRP in HCAP, on the other hand, had lower ability to identify patients at risk in COP.
Sofía Piñero-De Fuentes
Full Text Available Objetivo. Conocer la asociación entre consumo de marihuana, cocaína y/o bazuco, y causas de ingreso de pacientes al Hospital Central de Valencia, Venezuela. Material y métodos. Se estudiaron 148 individuos recibidos en el área de urgencias, debido a lesiones por agresión (LA, accidentes de tránsito (AT, accidentes de trabajo (ATB, lesión autoinfringida (LAU e intoxicaciones (INT. Se aplicó un cuestionario y un análisis toxicológicos. Resultados. Se encontró un consumo de drogas, solas y/o asociadas, de 23.6% (13.5% cocaína, 7.4% marihuana y 2.7% ambas. De los pacientes positivos para cocaína, 50% ingresaron por LA; 20% por INT; 10% por LAU; 5% por ATB, y 15% por otras causas. De los positivos para marihuana, 36.4% ingresaron por AT; 27.3% por ATB; 18% por LA; 9.09% por INT, y 9.09% por otros motivos. Los ingresos por LA fueron de 75%, y por ATB, de 25%, para drogas en combinación. El consumo alcohólico asociado a cocaína fue de 50%; a marihuana, de 9%; a combinación, de 25%. Conclusiones. Estos hallazgos demuestran que uno de cada cuatro ingresos por causa traumática está asociado al abuso de drogas, solas o en combinación, lo que revela una estrecha relación causa-efecto.Objective. To determine the association between patient admission due to trauma and the consumption of marihuana, cocaine and bazooka (basic cocaine paste at the Central Hospital of Valencia, Venezuela. Material and methods. 148 subjects were studied who had entered the emergency room due to lesions caused by aggression (AL, traffic accidents (TA, work-related accidents (WRA, self-inflicted injury (SII and intoxication (INT. A questionnaire was applied and toxicology analyses performed. Results. Drug consumption, alone or in combination, was found in 23.6% of individuals (13.5% cocaine, 7.4% marihuana and 2.7% both. Of the cocaine positive, 50% entered for AL, 20% for INT, 10% for SII, 5% for WRA and 15% for other causes. Of the marihuana positive, 36
Anorectal emergencies refer to anorectal disorders presenting with some alarming symptoms such as acute anal pain and bleeding which might require an immediate management. This article deals with the diagnosis and management of common anorectal emergencies such as acutely thrombosed external hemorrhoid, thrombosed or strangulated internal hemorrhoid, bleeding hemorrhoid, bleeding anorectal varices, anal fissure, irreducible or strangulated rectal prolapse, anorectal abscess, perineal necrotizing fasciitis (Fournier gangrene), retained anorectal foreign bodies and obstructing rectal cancer. Sexually transmitted diseases as anorectal non-surgical emergencies and some anorectal emergencies in neonates are also discussed. The last part of this review dedicates to the management of early complications following common anorectal procedures that may present as an emergency including acute urinary retention, bleeding, fecal impaction and anorectal sepsis. Although many of anorectal disorders presenting in an emergency setting are not life-threatening and may be successfully treated in an outpatient clinic, an accurate diagnosis and proper management remains a challenging problem for clinicians. A detailed history taking and a careful physical examination, including digital rectal examination and anoscopy, is essential for correct diagnosis and plan of treatment. In some cases, some imaging examinations, such as endoanal ultrasonography and computerized tomography scan of whole abdomen, are required. If in doubt, the attending physicians should not hesitate to consult an expert e.g., colorectal surgeon about the diagnosis, proper management and appropriate follow-up. PMID:27468181
José Ferreira Sarmento-Neto
Full Text Available Pain is an unpleasant sensation associated with a wide range of injuries and diseases, and affects approximately 20% of adults in the world. The discovery of new and more effective drugs that can relieve pain is an important research goal in both the pharmaceutical industry and academia. This review describes studies involving antinociceptive activity of essential oils from 31 plant species. Botanical aspects of aromatic plants, mechanisms of action in pain models and chemical composition profiles of the essential oils are discussed. The data obtained in these studies demonstrate the analgesic potential of this group of natural products for therapeutic purposes.
Cennini, E; Oortman Gerlings, P
On September 19th 2008, a technical fault was at the centre of a sequence of events which hampered the performance of certain equipments of the LHC 3-4 sector. Once the first effects of this sequence of events were detected, the behaviour of the CERN staff confronted to this complex and critical situation became the centre of the risk control process. During such a downward spiral the preparation of all stakeholders is essential and should respect the (apparently) basic principles of emergency preparedness. Preparedness towards normal operation of CERN facilities towards minor up to major emergency situations will be presented. The main technical, organisational and legal frameworks of the CERN emergency preparedness will be recalled, highlighting the CERN risk management and risk control strategy. Then, the sequence of events experienced by different stakeholders on September 19th will be reported, thus starting the learned lessons process.
Meyer, Markus R; Welter, Jessica; Weber, Armin A; Maurer, Hans H
To date, immunoassays are commercially available for quantification of valproic acid, salicylic acid, paracetamol, phenobarbital, phenytoin, and primidone. As they are no longer available, a fast, simple, and cost-effective quantitative gas chromatography-mass spectrometry (GC-MS) method was developed and fully validated for these drugs. After simple and fast liquid-liquid extraction, the samples were analyzed by GC-MS using the selected ion monitoring mode. The method was validated including the parameters selectivity, calibration model, precision, accuracy, and extraction efficiency. The above-mentioned analytes were separated within 8.5 minutes and sensitively detected. No interfering peaks were observed in blank samples from 8 different sources. The linearity ranges were 20-200 mg/L for valproic acid, 100-1200 mg/L for salicylic acid, 10-200 mg/L for paracetamol, 10-200 mg/L for phenobarbital, 4-20 mg/L for primidone, and 2.5-30 mg/L for phenytoin. Generally accepted criteria for accuracy and precision were fulfilled for all analytes using 6-point calibration. Even 1-point calibration was applicable for all analytes. The assay was successfully applied to analysis of real plasma samples and proficiency testing material. The assay described allowed fast and reliable determination of analytes relevant in the diagnosis of poisonings. Furthermore, time- and cost-saving 1-point calibration was shown to be suitable for daily routine work, especially in emergency cases.
Mannucci, Pier Mannuccio; Franchini, Massimo
Hemophilia B is a rare congenital bleeding disorder characterized by a deficiency of coagulation factor IX (FIX). Hemophilia B patients experience mild-to-severe bleeding complications according to the degree of FIX defect. Prophylaxis, with regular infusion of FIX concentrates, is nowadays, the mainstay of hemophilia care. However, because the relatively short half-life of such products necessitates frequent infusions and thus makes patients' adherence difficult, a number of strategies have been implemented to improve the pharmacokinetics of FIX clotting factors. This review summarizes the main results of Phase I/II and III studies on new FIX molecules engineered to have a longer half-life. Several technologies are being applied to extend FIX half-life, including Fc fusion, recombinant (r) albumin fusion and the addition of PEG polymers. By prolonging the FIX half-life up to 5 times, long-acting FIX products are expected to substantially improve the management of hemophilia B patients, allowing less frequent infusions and improving patients' adherence to prophylactic regimens and individualized treatments. Some of them are at an advanced stage of development, such as the rFIX-Fc which has been launched in March 2014. Along with the ongoing Phase III trials, long-term post-marketing surveillance studies are needed to assess their safety and effectiveness and their impact on patients' quality of life.
Mooney, Peter D; Hadjivassiliou, Marios; Sanders, David S
Coeliac disease is an autoimmune gluten sensitive enteropathy and is now known to affect 1% of the adult population. A gluten-free diet (GFD) should be curative; however, up to 30% of patients have persistent symptoms and many patients find the diet difficult to fully adhere to. Currently, there are no licensed therapeutic options for patients with coeliac disease outside of a GFD. This review will outline the case for alternative treatments and discuss the potential therapeutic targets. The products in the most advanced stage of development will be discussed in detail. There is clearly an unmet need for alternatives to a GFD for the treatment of coeliac disease. Oral glutenase supplements to improve the degradation of gluten into non-toxic peptides appear to be the most likely to provide a breakthrough in the treatment of coeliac disease; however, other modalities such as a therapeutic vaccine or zonulin inhibitors to reduce intestinal permeability have shown promising results.
Duong, David K; O'Sullivan, Patricia S; Satre, Derek D; Soskin, Philippa; Satterfield, Jason
Residency education is challenged by a shortage of personnel and time, particularly for teaching behavioral interventions such as screening, brief intervention, and referral to treatment (SBIRT) to reduce hazardous drinking and drug use. However, social workers may be well placed to teach SBIRT in clinical training settings. We describe a curriculum with social workers as SBIRT trainers of emergency medicine (EM) residents during actual clinical shifts in an EM residency training program. The curriculum required 1 EM faculty member working with social workers and 1 additional hour of formal residency conference teaching time. We implemented the curriculum at both a university tertiary care hospital emergency department and a county trauma center. We trained 8 social workers at both sites as SBIRT superusers to teach and assess EM resident SBIRT performance with actual patients. We measured the length and number of sessions to attain SBIRT competence, residents' satisfaction, and resident comments (coded by authors). Five of the 8 social workers trained residents between June 2013 and May 2014, 31 EM residents trained to a level indicating SBIRT competence with 114 patients. Each patient interaction averaged 8.8 minutes and residents averaged 3.13 patients. Twenty-four (77%) residents gave ratings of 1.58 (SD = .58) for the quality of teaching, 2.33 (SD = .87) for recommending the training to a colleague, 1.38 (SD = .49) for superusers' knowledge, 1.88 (SD = .95) for usefulness of instruction, 1.54 (SD = .72) for workplace learning, and 1.58 (SD = .78) for valuing learning from social workers (on a scale of 1 [very satisfied/strongly agree] to 5 [very dissatisfied/strongly disagree]). Residents preferred learning SBIRT during the 1st and 2nd training years and in the workplace. Social work colleagues can be effective in teaching SBIRT to residents in the workplace, and our residents highly valued learning from social workers, who all had prior training in
Abd Nasir Ibrahim; Azali Muhammad; Ab Razak Hamzah; Abd Aziz Mohamed; Mohammad Pauzi Ismail
The following subjects are discussed - Emergency Procedures: emergency equipment, emergency procedures; emergency procedure involving X-Ray equipment; emergency procedure involving radioactive sources
Kan, Hiromi; Imamura, Michio; Kawakami, Yoshiiku; Daijo, Kana; Teraoka, Yuji; Honda, Fumi; Nakamura, Yuki; Morio, Kei; Kobayashi, Tomoki; Nakahara, Takashi; Nagaoki, Yuko; Kawaoka, Tomokazu; Tsuge, Masataka; Aikata, Hiroshi; Hayes, Clair Nelson; Miki, Daiki; Ochi, Hidenori; Honda, Yoji; Mori, Nami; Takaki, Shintaro; Tsuji, Keiji; Chayama, Kazuaki
Combination of sofosbuvir plus ledipasvir therapy has been expected to enhance sustained virological response (SVR) rates in hepatitis C virus (HCV) genotype 1 chronic infected patients. We analyzed the emergence of drug resistance-associated variants (RAVs) in treatment failure and changes in lipid profiles in sofosbuvir/ledipasvir-treated patients. A total of 176 patients with chronic HCV genotype 1 infection without decompensated liver cirrhosis were treated with sofosbuvir/ledipasvir for 12 weeks. NS5A and NS5B RAVs were determined by either Invader assay or direct sequencing. Serum lipid-related markers were measured at the start of treatment and at week 4 in patients who received sofosbuvir/ledipasvir and ombitasvir/paritaprevir/ritonavir therapies. SVR was achieved in 94.9% (167 out of 176) of patients. SVR12 rate was 97.1% for patietns with low frequncy (75%) of NS5A RAVs. In multivariate regression analysis, higher albumin (odds ratio [OR] = 0.020 for presence; P = 0.007), and NS5A-L31/Y93 RAVs with a population frequency <75% (OR = 29.860 for presence; P = 0.023) were identified as significant independent predictors for SVR12. NS5A-Y93H substitutions were detected in all nine treatment failures at HCV relapse, and three out of six patients with NS5A inhibitor-naïve patients achieved additional NS5A RAVs. Serum low-density lipoprotein cholesterol and apolipoprotein B levels were significantly elevated at week 4 in sofosbuvir/ledipasvir-treated patients. These elevations were greater than in ombitasvir/paritaprevir/ritonavir-treated patients. In conclusion, NS5A multi-RAVs are likely to develop in patients who fail to respond to sofosbuvir/ledipasvir therapy. Inhibition of HCV replication with sofosbuvir might affect lipid metabolism. © 2017 Wiley Periodicals, Inc.
Blouin, Karine; Leclerc, Pascale; Morissette, Carole; Roy, Élise; Blanchette, Caty; Parent, Raymond; Serhir, Bouchra; Alary, Michel
Recent analyses have shown an emerging positive association between sex work and human immunodeficiency virus (HIV) incidence among people who inject drugs (PWIDs) in the SurvUDI network. Participants who had injected in the past 6 months were recruited across the Province of Quebec and in the city of Ottawa, mainly in harm reduction programs. They completed a questionnaire and provided gingival exudate for HIV antibody testing. The associations with HIV seroconversion were tested with a Cox proportional hazard model using time-dependent covariables including the main variable of interest, sexual activity (sex work; no sex work; sexually inactive). The final model included significant variables and confounders of the associations with sexual activity. Seventy-two HIV seroconversions were observed during 5239.2 person-years (py) of follow-up (incidence rates: total = 1.4/100 py; 95% confidence interval [CI], 1.1-1.7; sex work = 2.5/100 py; 95% CI, 1.5-3.6; no sex work = 0.8/100 py; 95% CI, 0.5-1.2; sexually inactive = 1.8/100 py; 95% CI, 1.1-2.5). In the final multivariate model, HIV incidence was significantly associated with sexual activity (sex work: adjusted hazard ratio [AHR], 2.19; 95% CI, 1.13-4.25; sexually inactive: AHR, 1.62; 95% CI, 0.92-2.88), and injection with a needle/syringe used by someone else (AHR, 2.84; 95% CI, 1.73-4.66). Sex work is independently associated with HIV incidence among PWIDs. At the other end of the spectrum of sexual activity, sexually inactive PWIDs have a higher HIV incidence rate, likely due to more profound dependence leading to increased vulnerabilities, which may include mental illness, poverty, and social exclusion. Further studies are needed to understand whether the association between sex work and HIV is related to sexual transmission or other vulnerability factors.
Full Text Available In recent years, the surprising progress made in other areas of hematology (advances in the understanding of leukemogenesis, improved transplant techniques has been conspicuously absent in the management of hematologic emergencies. And yet, every step toward greater knowledge, every new treatment option will be of little value unless we are able to manage the acute complications of hematologic diseases. These complications are better defined as hematologic emergencies, and they are characterized by a high rate of mortality. This review is based on a search of the literature that was initially confined to articles published in the journal Hematology from 2000 to 2009. The search was then extended to the Cochrane Library and to Pub Med in February 2010 with the following Keywords emergencies; urgencies; hematology. The same key words were employed in a search of the archives of Blood and the New England Journal of Medicine from 2000 to 2010. The results confirm that hematologic emergencies can be caused by hematologic malignancies as well as by non-neoplastic hematologic diseases. Within the former category; this review examines the causes; manifestations; treatment and prevention of disseminated intravascular coagulation; superior vena caval syndrome; spinal cord compression; tumor lysis syndrome; hyperleukocytosis; and hypercalcemia. We also review emergency situations associated with non-neoplatic haematological diseases; such as thrombotic thrombocytopenic purpura; drug-induced hemolytic anemia; and acute sickle-cell crisis.
Full Text Available ... Twitter YouTube Flickr RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts ... to HIV and progression of AIDS. Drugs of abuse and HIV both affect the brain. Research has ...
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Full Text Available ... Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl ... AIDS (acquired immune deficiency syndrome). AIDS is a disease of the immune system for which there is ...
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.
Mohler, S. R.; Nicogossian, A.; Margulies, R. A.
Problems related to immediate medical care in case of in-flight emergencies are discussed with reference to such critical types of medical emergencies as obstructed airway, cardiac dysfunction, trauma, hemorrhage, hypoxia, and pain. It is shown that training flight attendants to deal with in-flight medical emergencies and to use first-aid support equipment and essential and useful drugs may later help with stabilization of a victim and allow continuing the flight to the scheduled destination without the need for a diverted landing. Among the steps suggested in order to upgrade inflight welfare and safety of passengers are the development of an advisory circular by the FAA covering standardized training for flight attendants, regulatory action requiring upgrading of the present rudimentary first-aid kit, and the enactment of Good Samaritan legislation by the U.S. Government.
Vishvakarama Prabhakar; Agarwal Shivendra; Sharma Ritika; Saurabh Sharma
Various new technologies have been developed for the transdermal delivery of some important drugs. Today about 74% of drugs are taken orally and are found not to be as effective as desired. To improve such characters transdermal drug delivery system was emerged. Drug delivery through the skin to achieve a systemic effect of a drug is commonly known as transdermal drug delivery and differs from traditional topical drug delivery. Transdermal drug delivery systems (TDDS) are dosage forms involve...
Max Joseph Herman
Full Text Available Although essentially not all therapies need drug intervention, drugs is still an important components in health sector, either in preventive, curative, rehabilitative or promotion efforts. Hence the access to drugs is a main problem, either in international or national scale even to the smallest unit. The problem on access to drugs is very complicated and cannot be separated especially from pharmacy management problems; moreover in general from the overall lack of policy development and effective of health policy, and also the implementation process. With the policy development and effective health policy, rational drug uses, sufficient health service budget so a country can overcome the health problems. Besides infrastructures, regulations, distribution and cultural influences; the main obstacles for drug access is drugs affordability if the price of drugs is an important part and determined by many factors, especially the drug status whether is still patent orgenerics that significantly decrease cost of health cares and enhance the drugs affordability. The determination of essential drug prices in developing countries should based on equity principal so that poor people pay cheaper and could afford the essential drugs. WHO predicts two third of world population can not afford the essential drugs in which in developing countries, some are because of in efficient budget allocation in consequence of drug distribution management, including incorrect selection and allocation and also irrational uses. In part these could be overcome by enhancing performances on the allocation pharmacy needs, including the management of information system, inventory management, stock management and the distribution. Key words: access, drugs, essential drugs, generic drugs
Lynch, Caroline A; Pearce, Richard; Pota, Hirva; Egwang, Connie; Egwang, Thomas; Bhasin, Amit; Cox, Jonathan; Abeku, Tarekegn A; Roper, Cally
emergence of a regional cluster of I164L in SW Uganda and Rwanda indicates that transmission of I164L is facilitated by strong drug pressure in low transmission areas potentially catalysed in those areas by travel and the importation of parasites from relatively higher transmission settings.
Full Text Available Emergency contraception refers to any device or drug that is used as an emergency procedure to prevent pregnancy after unprotected sexual intercourse.The first method of emergency contraception was high dose of estrogen. Concern about side effects led to subsequent development of the so-called Yuzpe regimen which combined ethinil estradiol with levonorgestrel and levonorgestrel alone. Less convenient to use is the copper intauterine contraceptive device.It is known that in some women sexual steroids may inhibit or delay ovulation and may interfere with ovum and sperm transport and implantation. Copper intrauterine device causes a foreign-body effect on the endometrium and a direct toxic effect to sperm and blastocyst.The Yuzpe regimen reduces the risk of pregnancy after a single act of sexual intercourse by about 75% and the levonorgestrel alone by about 85%. The copper intrauterine device is an extremely effective method for selected patients.Nausea and vomiting are common among women using the Yuzpe regimen and considerably less common among women using levonorgestrel alone regimen.Emergency contraception is relatively safe with no contraindications except pregnancy. It is ineffective if a woman is pregnant. There is no need for a medical hystory or a phisical examination before providing emergency contraceptive pills. They are taken long before organogenesis starts, so they should not have a teratogenic effect.Counseling should include information about correct use of the method, possible side effects and her preferences for regular contraception.Unintended pregnancy is a great problem. Several safe, effective and inexpensive methods of emergency contraception are available including Yuzpe regimen, levonorges-trel-only regimen and copper intrauterine device.
... for PATIENTS and their FAMILIES TREATMENT OF ESSENTIAL TREMOR This fact sheet is provided to help you understand which therapies help treat essential tremor. Neurologists from the American Academy of Neurology are ...
Lerch, Michael M.; Hansen, Mickel J.; van Dam, Gooitzen M.; Szymanski, Wiktor; Feringa, Ben L.
The field of photopharmacology uses molecular photoswitches to establish control over the action of bioactive molecules. It aims to reduce systemic drug toxicity and the emergence of resistance, while achieving unprecedented precision in treatment. By using small molecules, photopharmacology
Halskov, Kim; Dalsgård, Peter
The development of new ideas is an essential concern for many design projects. There are, however, few in-depth studies of how such ideas emerge within these contexts. In this article we offer an analysis of the emergence of ideas from specific sources of inspiration, as they arise through...
Ellner, Jerrold J
Surveillance studies and outbreak investigations indicate that an extensively drug-resistant (XDR) form of tuberculosis (TB) is increasing in prevalence worldwide. In outbreak settings among HIV-infected, there is a high-case fatality rate. Better outcomes occur in HIV-uninfected, particularly if drug susceptibility test (DST) results are available rapidly to allow tailoring of drug therapy. This review will be presented in two segments. The first characterizes the problem posed by XDR-TB, addressing the epidemiology and evolution of XDR-TB and treatment outcomes. The second reviews technologic advances that may contribute to the solution, new diagnostics, and advances in understanding drug resistance and in the development of new drugs.
Duong, Mai; Moles, Rebekah J; Chaar, Betty; Chen, Timothy F
To explore the perspectives of a diverse group of stakeholders engaged in medicines decision making around what constitutes an "essential" medicine, and how the Essential Medicines List (EML) concept functions in a high income country context. In-depth qualitative semi-structured interviews were conducted with 32 Australian stakeholders, recognised as decision makers, leaders or advisors in the area of medicines reimbursement or supply chain management. Participants were recruited from government, pharmaceutical industry, pharmaceutical wholesale/distribution companies, medicines non-profit organisations, academic health disciplines, hospitals, and consumer groups. Perspectives on the definition and application of the EML concept in a high income country context were thematically analysed using grounded theory approach. Stakeholders found it challenging to describe the EML concept in the Australian context because many perceived it was generally used in resource scarce settings. Stakeholders were unable to distinguish whether nationally reimbursed medicines were essential medicines in Australia. Despite frequent generic drug shortages and high prices paid by consumers, many struggled to describe how the EML concept applied to Australia. Instead, broad inclusion of consumer needs, such as rare and high cost medicines, and consumer involvement in the decision making process, has led to expansive lists of nationally subsidised medicines. Therefore, improved communication and coordination is needed around shared interests between stakeholders regarding how medicines are prioritised and guaranteed in the supply chain. This study showed that decision-making in Australia around reimbursement of medicines has strayed from the fundamental utilitarian concept of essential medicines. Many stakeholders involved in medicine reimbursement decisions and management of the supply chain did not consider the EML concept in their approach. The wide range of views of what stakeholders
Full Text Available To explore the perspectives of a diverse group of stakeholders engaged in medicines decision making around what constitutes an "essential" medicine, and how the Essential Medicines List (EML concept functions in a high income country context.In-depth qualitative semi-structured interviews were conducted with 32 Australian stakeholders, recognised as decision makers, leaders or advisors in the area of medicines reimbursement or supply chain management. Participants were recruited from government, pharmaceutical industry, pharmaceutical wholesale/distribution companies, medicines non-profit organisations, academic health disciplines, hospitals, and consumer groups. Perspectives on the definition and application of the EML concept in a high income country context were thematically analysed using grounded theory approach.Stakeholders found it challenging to describe the EML concept in the Australian context because many perceived it was generally used in resource scarce settings. Stakeholders were unable to distinguish whether nationally reimbursed medicines were essential medicines in Australia. Despite frequent generic drug shortages and high prices paid by consumers, many struggled to describe how the EML concept applied to Australia. Instead, broad inclusion of consumer needs, such as rare and high cost medicines, and consumer involvement in the decision making process, has led to expansive lists of nationally subsidised medicines. Therefore, improved communication and coordination is needed around shared interests between stakeholders regarding how medicines are prioritised and guaranteed in the supply chain.This study showed that decision-making in Australia around reimbursement of medicines has strayed from the fundamental utilitarian concept of essential medicines. Many stakeholders involved in medicine reimbursement decisions and management of the supply chain did not consider the EML concept in their approach. The wide range of views of
Full Text Available INTRODUCTION: Inadequate access to essential medicines is a common issue within developing countries. Policy response is constrained, amongst other factors, by a dearth of in-depth country level evidence. We share here i gaps related to access to essential medicine in Pakistan; and ii prioritization of emerging policy and research concerns. METHODS: An exploratory research was carried out using a health systems perspective and applying the WHO Framework for Equitable Access to Essential Medicine. Methods involved key informant interviews with policy makers, providers, industry, NGOs, experts and development partners, review of published and grey literature, and consultative prioritization in stakeholder's Roundtable. FINDINGS: A synthesis of evidence found major gaps in essential medicine access in Pakistan driven by weaknesses in the health care system as well as weak pharmaceutical regulation. 7 major policy concerns and 11 emerging research concerns were identified through consultative Roundtable. These related to weaknesses in medicine registration and quality assurance systems, unclear and counterproductive pricing policies, irrational prescribing and sub-optimal drug availability. Available research, both locally and globally, fails to target most of the identified policy concerns, tending to concentrate on irrational prescriptions. It overlooks trans-disciplinary areas of policy effectiveness surveillance, consumer behavior, operational pilots and pricing interventions review. CONCLUSION: Experience from Pakistan shows that policy concerns related to essential medicine access need integrated responses across various components of the health systems, are poorly addressed by existing evidence, and require an expanded health systems research agenda.
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REA, Editors of
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Electric Circuits I includes units, notation, resistive circuits, experimental laws, transient circuits, network theorems, techniques of circuit analysis, sinusoidal analysis, polyph
REA, Editors of
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Calculus III includes vector analysis, real valued functions, partial differentiation, multiple integrations, vector fields, and infinite series.
Milewski, Emil G
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Statistics I covers include frequency distributions, numerical methods of describing data, measures of variability, parameters of distributions, probability theory, and distributions.
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Pre-Calculus reviews sets, numbers, operations and properties, coordinate geometry, fundamental algebraic topics, solving equations and inequalities, functions, trigonometry, exponents
REA, The Editors of
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Transport Phenomena II covers forced convention, temperature distribution, free convection, diffusitivity and the mechanism of mass transfer, convective mass transfer, concentration
REA, Editors of
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Differential Equations I covers first- and second-order equations, series solutions, higher-order linear equations, and the Laplace transform.
REA, The Editors of
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Heat Transfer II reviews correlations for forced convection, free convection, heat exchangers, radiation heat transfer, and boiling and condensation.
REA, The Editors of; Staff of Research Education Association
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Numerical Analysis II covers simultaneous linear systems and matrix methods, differential equations, Fourier transformations, partial differential equations, and Monte Carlo methods.
REA, Editors of
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Algebra & Trigonometry II includes logarithms, sequences and series, permutations, combinations and probability, vectors, matrices, determinants and systems of equations, mathematica
Lutfiyya, Lutfi A
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Modern Algebra includes set theory, operations, relations, basic properties of the integers, group theory, and ring theory.
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Business Statistics I includes descriptive statistics, introduction to probability, probability distributions, sampling and sampling distributions, interval estimation, and hypothesis t
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Computer Science I includes fundamental computer concepts, number representations, Boolean algebra, switching circuits, and computer architecture.
Woods, Hannah; Oronsaye, Efosa; Bali, Anjli; Rajakulasingam, Yathavan; Lee, Taehoon; Umali, Norman; Cohen, Eyal; Finkelstein, Yaron; Offringa, Martin; Persaud, Nav
Worldwide, many countries have developed a list of essential medicines for children to improve prescribing. We aimed to create an essential medicines list for children in Canada. We adapted the previously created preliminary list of essential medicines for adults in Canada and the WHO Model List of Essential Medicines for Children to create a provisional list of essential medicines for children in Canada. Canadian clinicians made suggestions for changes. Literature relevant to each suggestion was presented to clinician-scientists, who used a modified nominal group technique to make recommendations on the suggestions. Ontario Public Drug Programs prescription data were reviewed to identify commonly prescribed medications missing from the list. Literature relevant to these medications was shared with a clinician-scientist review panel to determine which should be added, and a revised list was developed. A total of 76 items were removed from the list of essential medicines for adults in Canada because they were not indicated for use in children or were not relevant in the Canadian health care context; 7 medications were added to the child list based on Ontario Public Drugs Programs prescribing data and clinician-scientist review. Suggestions to add, remove or substitute medications were made by peer-reviewers and resulted in removal of 1 medication and replacement of 1 medication. The process produced a provisional list of 67 essential medications for children. A provisional list of 67 essential medicines for children was created through a peer-reviewed, multistep process based on current clinical evidence, Canadian clinical practice guidelines and historical prescribing data. It is publicly posted at http://cleanmeds.ca/. The list should be further developed based on wider input and should be continuously revised based on emerging evidence of the safety and effectiveness of these medicines in all pediatric age groups. Copyright 2018, Joule Inc. or its licensors.
Coleman, Michael D
.... Completely revised and updated throughout, the new edition focuses only on essential chemical detail and includes patient case histories to illustrate the clinical consequences of changes in drug...
Kobayashi, K.; Ehrlich, S.D.; Albertini, A.
To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximate to4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were...... predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related...... to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from...
: Environmental Documents, Reports LANL Home Calendar Search Contacts Resources Â» Emergency Communication Emergency Communication Stay informed of emergencies, weather delays, closures, other alerts. Find links to
İLHAN, Mustafa Necmi
The NationalStrategy Document on Drugs and Emergency Action Plan started with thecontributions of all the relevant institutions within the year of 2014 wasprepared and after that in accordance with the Prime Ministry Notice entitledFight Against Drugs published within this scope, the committees for FightAgainst Drugs were established (under the presidency of Deputy Prime Ministerand with the help of Ministry of Health, Ministry of Justice, Ministry of Laborand Social Security, Ministry of Fam...
Hegedüs, Csilla; Truta-Feles, Krisztina; Antalffy, Géza; Várady, György; Német, Katalin; Ozvegy-Laczka, Csilla; Kéri, György; Orfi, László; Szakács, Gergely; Settleman, Jeffrey; Váradi, András; Sarkadi, Balázs
Human ABCG2 is a plasma membrane glycoprotein that provides physiological protection against xenobiotics. ABCG2 also significantly influences biodistribution of drugs through pharmacological tissue barriers and confers multidrug resistance to cancer cells. Moreover, ABCG2 is the molecular determinant of the side population that is characteristically enriched in normal and cancer stem cells. Numerous tumors depend on unregulated EGFR signaling, thus inhibition of this receptor by small molecular weight inhibitors such as gefitinib, and the novel second generation agents vandetanib, pelitinib and neratinib, is a promising therapeutic option. In the present study, we provide detailed biochemical characterization regarding the interaction of these EGFR inhibitors with ABCG2. We show that ABCG2 confers resistance to gefitinib and pelitinib, whereas the intracellular action of vandetanib and neratinib is unaltered by the presence of the transporter. At higher concentrations, however, all these EGFR inhibitors inhibit ABCG2 function, thereby promoting accumulation of ABCG2 substrate drugs. We also report enhanced expression of ABCG2 in gefitinib-resistant non-small cell lung cancer cells, suggesting potential clinical relevance of ABCG2 in acquired drug resistance. Since ABCG2 has important impact on both the pharmacological properties and anti-cancer efficiencies of drugs, our results regarding the novel EGFR inhibitors should provide useful information about their therapeutic applicability against ABCG2-expressing cancer cells depending on EGFR signaling. In addition, the finding that these EGFR inhibitors efficiently block ABCG2 function may help to design novel drug-combination therapeutic strategies. Copyright © 2012 Elsevier Inc. All rights reserved.
herbal forms of medicine and relaxation (such as aromatherapy), and .... (Flower bud, aerial part, cell suspension) α-farnesene 0-91, 3-OH .... (Leaf, stem); camphor 32, pulegone 15, 1,8-cineole 13. n.s. ..... Volatile oil-containing drugs and essential oils have ...... Achillea asplenifolia Vent. through multiple shoot regeneration.
Michaelis, M.; Rothweiler, F.; Barth, S.; Cinatl, J.; van Rikxoort, M.; Loeschmann, N.; Voges, Y.; Breitling, R.; von Deimling, A.; Roedel, F.; Weber, K.; Fehse, B.; Mack, E.; Stiewe, T.; Doerr, H. W.; Speidel, D.; Cinatl, J.; Cinatl jr., J.; Stephanou, A.
Six p53 wild-type cancer cell lines from infrequently p53-mutated entities (neuroblastoma, rhabdomyosarcoma, and melanoma) were continuously exposed to increasing concentrations of the murine double minute 2 inhibitor nutlin-3, resulting in the emergence of nutlin-3-resistant, p53-mutated sublines
Williams, Vernon B
Sports neurology is an emerging area of subspecialty. Neurologists and non-neurologists evaluating and managing individuals participating in sports will encounter emergencies that directly or indirectly involve the nervous system. Since the primary specialty of sports medicine physicians and other practitioners involved in the delivery of medical care to athletes in emergency situations varies significantly, experience in recognition and management of neurologic emergencies in sports will vary as well. This article provides a review of information and elements essential to neurologic emergencies in sports for the practicing neurologist, although content may be of benefit to readers of varying background and expertise. Both common neurologic emergencies and less common but noteworthy neurologic emergencies are reviewed in this article. Issues that are fairly unique to sports participation are highlighted in this review. General concepts and principles related to treatment of neurologic emergencies that are often encountered unrelated to sports (eg, recognition and treatment of status epilepticus, increased intracranial pressure) are discussed but are not the focus of this article. Neurologic emergencies can involve any region of the nervous system (eg, brain, spine/spinal cord, peripheral nerves, muscles). In addition to neurologic emergencies that represent direct sports-related neurologic complications, indirect (systemic and generalized) sports-related emergencies with significant neurologic consequences can occur and are also discussed in this article. Neurologists and others involved in the care of athletes should consider neurologic emergencies in sports when planning and providing medical care.
REA, The Editors of
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Physics I includes vectors and scalars, one-dimensional motion, plane motion, dynamics of a particle, work and energy, conservation of energy, dynamics of systems of particles, rotation
REA, The Editors of
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Electronics II covers operational amplifiers, feedback and frequency compensation of OP amps, multivibrators, logic gates and families, Boolean algebra, registers, counters, arithmet
REA, The Editors of
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Thermodynamics I includes review of properties and states of a pure substance, work and heat, energy and the first law of thermodynamics, entropy and the second law of thermodynamics
Ackermann, Ernest C
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. C Programming Language discusses fundamental notions, data types and objects, expressions, statements, declarations, function and program structure, the preprocessor, and the standar
REA, The Editors of
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Electronics I covers fundamentals of semiconductor devices, junction diodes, bipolar junction transistors, power supplies, multitransistor circuits, small signals, low-frequency anal
REA, The Editors of
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Thermodynamics II includes review of thermodynamic relations, power and refrigeration cycles, mixtures and solutions, chemical reactions, chemical equilibrium, and flow through nozzl
Milewski, Emil G
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Group Theory I includes sets and mapping, groupoids and semi-groups, groups, isomorphisms and homomorphisms, cyclic groups, the Sylow theorems, and finite p-groups.
Solomon, Alan D
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Boolean Algebra includes set theory, sentential calculus, fundamental ideas of Boolean algebras, lattices, rings and Boolean algebras, the structure of a Boolean algebra, and Boolean
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Laplace Transforms includes the Laplace transform, the inverse Laplace transform, special functions and properties, applications to ordinary linear differential equations, Fourier tr
REA, The Editors of
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Physical Chemistry II includes reaction mechanisms, theoretical approaches to chemical kinetics, gravitational work, electrical and magnetic work, surface work, kinetic theory, collisional and transport properties of gases, statistical mechanics, matter and waves, quantum mechanics, and rotations and vibrations of atoms and molecules.
Milewski, Emil G
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Statistics II discusses sampling theory, statistical inference, independent and dependent variables, correlation theory, experimental design, count data, chi-square test, and time se
REA, Editors of
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Algebra & Trigonometry I includes sets and set operations, number systems and fundamental algebraic laws and operations, exponents and radicals, polynomials and rational expressions, eq
REA, The Editors of
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Geometry I includes methods of proof, points, lines, planes, angles, congruent angles and line segments, triangles, parallelism, quadrilaterals, geometric inequalities, and geometric
REA, The Editors of
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Transport Phenomena I includes viscosity, flow of Newtonian fluids, velocity distribution in laminar flow, velocity distributions with more than one independent variable, thermal con
Smolarski, Dennis C
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Data Structures II includes sets, trees, advanced sorting, elementary graph theory, hashing, memory management and garbage collection, and appendices on recursion vs. iteration, alge
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Computer Science II includes organization of a computer, memory and input/output, coding, data structures, and program development. Also included is an overview of the most commonly
Smolarski, Dennis C
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Data Structures I includes scalar variables, arrays and records, elementary sorting, searching, linked lists, queues, and appendices of binary notation and subprogram parameter passi
Milewski, Emil G
REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Set Theory includes elementary logic, sets, relations, functions, denumerable and non-denumerable sets, cardinal numbers, Cantor's theorem, axiom of choice, and order relations.
Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...
... SUBSCRIBE Emergency 101 Share this! Home » Emergency 101 Childhood Emergencies Keeping children healthy and safe is every ... and tools to prevent, recognize and address a childhood emergency is the first step in keeping your ...
... The Marfan Foundation Marfan & Related Disorders What is Marfan Syndrome? What are Related Disorders? What are the Signs? ... Emergencies Eye Emergencies Lung Emergencies Surgeries Eye Emergencies Marfan syndrome significantly increases your risk of retinal detachment, a ...
Morning-after pill; Postcoital contraception; Birth control - emergency; Plan B; Family planning - emergency contraception ... IUD placed inside the uterus CHOICES FOR EMERGENCY CONTRACEPTION Two emergency contraceptive pills may be bought without a prescription. ...
Delves, Peter J; Roitt, Ivan M
... of the immune system, the hallmark easy-reading style of Roitt's Essential Immunology clearly explains the key principles needed by medical and health sciences students, from the basis of immunity to clinical applications...
... the same for many years; and, in rare cases, improve spontaneously. Clinical Trials Throughout the U.S. and Worldwide NINDS Clinical Trials Related ... Definition Benign essential blepharospasm (BEB) is a progressive neurological ...
Kotler, P.J.; Keller, K.; Robben, H.S.J.
'Marketingmanagement, de essentie' biedt een volledige introductie in modern marketingmanagement. De nieuwste concepten en onderzoeksresultaten komen aan bod. Zo wordt veel aandacht besteed aan holistische marketing en is de impact van technologische ontwikkelingen op hedendaagse marketing in deze
Kotler, P.J.; Keller, K.; Robben, H.S.J.
'Marketingmanagement, de essentie' biedt een volledige introductie in modern marketingmanagement. De nieuwste concepten en onderzoeksresultaten komen aan bod. Zo wordt veel aandacht besteed aan holistische marketing en is de impact van technologische ontwikkelingen op hedendaagse marketing in deze
José Díaz Novás
Full Text Available INTRODUCCIÓN: los servicios de urgencias requieren de un soporte de exámenes y medicamentos que apoyen su capacidad resolutiva y que se utilicen con eficiencia. OBJETIVOS: identificar el uso de exámenes complementarios y medicamentos, sus costos y relación con la morbilidad observada. MÉTODOS: se realizó un estudio observacional, descriptivo, longitudinal y retrospectivo sobre la utilización de exámenes complementarios, medicamentos y sus costos, en el servicio de urgencias del Policlínico-Hospital "Raúl Gómez García", en el período de enero a marzo de 2007. Se correlacionó el uso de exámenes y medicamentos con la morbilidad observada. RESULTADOS: el chequeo de la tensión arterial, las infecciones respiratorias agudas y las crisis agudas de asma bronquial fueron las causas más frecuentes de consulta. Se observó 1 de cada 21,3 pacientes atendidos. El 19,7 % de los pacientes requirieron la realización de exámenes complementarios. El laboratorio clínico, fue el medio diagnóstico más utilizado. Los medicamentos más utilizados fueron: el aerosol de salbutamol, la dipirona y la aminofilina. La indicación de exámenes y medicamentos, generalmente, estuvo justificada por los problemas de salud atendidos. Los exámenes de rayos X, los electrocardiogramas y entre los medicamentos la hidrocortisona, fueron los que más gastos ocasionaron. CONCLUSIONES: la morbilidad observada estuvo acorde con lo esperado para un servicio de urgencias primario, y justificó, en la mayoría de los casos, los exámenes y medicamentos utilizados. El empleo racional del método clínico puede mejorar el uso de recursos y los costos.INTRODUCTION: the emergency services require tests and drugs that support their resolving capacity and that be used with efficiency. OBJECTIVES: to identify the use of complementary tests and drugs, their costs and their connection with the morbidity observed. METHODS: an observational descriptive, longitudinal and
Essential equivalence: the objectives and requirements of a stategic nuclear policy: a perspective on the evolution of US strategic nuclear policy, and an assessment of present and emerging US strategic policy and force stucture options
This study provides a discussion of the origins and evolution of US strategic nuclear policy, the objectives an requirements of US nuclear forces, and an assessment of present and emerging US stategic nuclear policy and force structure options. It identifies the distinctive phases of US strategic nuclear policy, the conditions of the military environments in which those policies were developed, the interaction of US-Soviet strategic force and arms control processes during these phases, and the domestic debates which have accompanied US strategic nuclear policy developments. In particular, the study focuses on the major contending views which continue to characterize the debate concerning US strategic nuclear policy. The study assesses the implications of the contending views represented in what is commonly referred to as the counterforce-countervalue debate, particularly as they relate to the perception of what constitutes a credible US deterrent posture, and the corresponding alternatives that these views bring with them for making US strategic nuclear policy and force structure decisions. The arms control process, in general, and SALT I and SALT II in particular, is discussed as an integral and dynamic component of the strategic debate, fundamentally affecting the nation's security policies. The implications of modern weapons technology, and the problems inherent in preserving strategic stability between adversary nations with asymmetries in military force structures and doctrines, are also discussed. Further, the study focuses on the question of whether or not nuclear superiority can be considered relevant under the contemporary international conditions
Job titles like ""Technical Architect"" and ""Chief Architect"" nowadays abound in software industry, yet many people suspect that ""architecture"" is one of the most overused and least understood terms in professional software development. Gorton's book tries to resolve this dilemma. It concisely describes the essential elements of knowledge and key skills required to be a software architect. The explanations encompass the essentials of architecture thinking, practices, and supporting technologies. They range from a general understanding of structure and quality attributes through technical i
Full Text Available ... Parents & Educators Children & Teens Search Connect with NIDA : Facebook LinkedIn Twitter YouTube Flickr RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts ...
Full Text Available ... Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA ( ... materials include print PSAs, Web banner PSAs, promo cards, and posters. Videos The campaign includes the "After ...
Drake, Penelope M; Rabuka, David
Antibody-drug conjugates (ADCs) have become de rigueur for pharmaceutical oncology drug development pipelines. There are more than 40 ADCs undergoing clinical trials and many more in preclinical development. The field has rushed to follow the initial successes of Kadcyla™ and Adcetris™, and moved forward with new targets without much pause for optimization. In some respects, the ADC space has become divided into the clinical realm-where the proven technologies continue to represent the bulk of clinical candidates with a few exceptions-and the research realm-where innovations in conjugation chemistry and linker technologies have suggested that there is much room for improvement in the conventional methods. Now, two and four years after the approvals of Kadcyla™ and Adcetris™, respectively, consensus may at last be building that these two drugs rely on rather unique target antigens that enable their success. It is becoming increasingly clear that future target antigens will require additional innovative approaches. Next-generation ADCs have begun to move out of the lab and into the clinic, where there is a pressing need for continued innovation to overcome the twin challenges of safety and efficacy. Copyright © 2015 Elsevier Ltd. All rights reserved.
Full Text Available ... Twitter YouTube Flickr RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs ... from the Director of the National Institute on Drug Abuse, Dr. Nora D. Volkow. Message from the Director ...
Margot, Nicolas; Cox, Stephanie; Das, Moupali; McCallister, Scott; Miller, Michael D; Callebaut, Christian
The single tablet regimen (STR) composed of elvitegravir (E), cobicistat (C), emtricitabine (F), and tenofovir alafenamide (TAF) (E/C/F/TAF) was compared to the STR composed of E, C, F, and tenofovir disoproxil fumarate (TDF) (E/C/F/TDF) in 2 phase 3 studies in 1733 HIV-1 infected treatment-naïve adults. Superior efficacy of E/C/F/TAF compared to E/C/F/TDF was demonstrated at Week 144 with 84% treatment success compared to 80%, respectively, along with significantly better outcomes of bone and renal safety. Analyze the emergence of HIV-1 resistance in treatment-naïve adults receiving E/C/F/TAF for 144 weeks. We conducted an integrated resistance analysis of the 2 Phase 3 studies, comprising pretreatment HIV-1 sequencing for all participants (N = 1733) and post-baseline HIV-1 resistance analysis for participants with virologic failure (HIV-1 RNA ≥400 copies/mL). Primary resistance-associated mutations (RAMs) were observed pre-treatment in 7.4% (NRTI-RAMs), 18.1% (NNRTI-RAMs), and 3.3% (PI-RAMs) of enrolled subjects. Baseline HIV-1 subtype or pre-existing RAMs did not affect E/C/F/TAF treatment response at week 144. Virologic failure resistance analyses were conducted for 28/866 (3.2%) and 30/867 (3.5%) patients in the E/C/F/TAF and E/C/F/TDF arms, respectively. Over the 3-year study, the rate of resistance emergence remained low at 1.4% in each group (12/866 in E/C/F/TAF; 12/867 in E/C/F/TDF). Resistant virus emerged in 24 patients who developed resistance to antiretrovirals in the regimens (E/C/F/TAF: M184V/I [1.3%], INSTI-RAMs [0.9%], K65R/N [0.2%]; E/C/F/TDF: M184V/I [1.0%], INSTI-RAMs [0.9%], K65R/N [0.5%]). Resistance emergence was rare (1.4%) with similar patterns of emergent mutations in both groups. M184V/I was the most prevalent RAM (1.2% overall). Copyright © 2018 Elsevier B.V. All rights reserved.
Nguyen, Thi Van Anh; Anthony, Richard M; Bañuls, Anne-Laure; Vu, Dinh Hoa; Alffenaar, Jan-Willem C
Bedaquiline, a new anti-tuberculosis drug, has already been used in more than 50 countries. The emergence of bedaquiline resistance is alarming, as it may result in the rapid loss of this new drug. This paper aims to review currently identified mechanisms of resistance, the emergence of bedaquiline resistance, and discuss strategies to delay the resistance acquisition. In vitro and clinical studies as well as reports from the compassionate use have identified the threat of bedaquiline resistance and cross-resistance with clofazimine, emphasizing the crucial need for the systematic surveillance of resistance. Currently known mechanisms of resistance include mutations within the atpE, Rv0678 and pepQ genes. The development of standardized drug susceptibility testing (DST) for bedaquiline is urgently needed.Understanding any target and non-target based mechanisms is essential to minimize the resistance development and treatment failure, help to develop appropriate DST for bedaquiline and genetic based resistance screening. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: email@example.com.
Hamdam, Junnat; Sethu, Swaminathan; Smith, Trevor; Alfirevic, Ana; Alhaidari, Mohammad; Atkinson, Jeffrey; Ayala, Mimieveshiofuo; Box, Helen; Cross, Michael; Delaunois, Annie; Dermody, Ailsa; Govindappa, Karthik; Guillon, Jean-Michel; Jenkins, Rosalind; Kenna, Gerry; Lemmer, Björn; Meecham, Ken; Olayanju, Adedamola; Pestel, Sabine; Rothfuss, Andreas
Safety pharmacology (SP) is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials. SP studies are described in the International Conference on Harmonisation (ICH) S7A and S7B guidelines. The core battery and supplemental SP studies evaluate effects of a new chemical entity (NCE) at both anticipated therapeutic and supra-therapeutic exposures on major organ systems, including cardiovascular, central nervous, respiratory, renal and gastrointestinal. This review outlines the current practices and emerging concepts in SP studies including frontloading, parallel assessment of core battery studies, use of non-standard species, biomarkers, and combining toxicology and SP assessments. Integration of the newer approaches to routine SP studies may significantly enhance the scope of SP by refining and providing mechanistic insight to potential adverse effects associated with test compounds. - Highlights: • SP — mandatory non-clinical risk assessments performed during drug development. • SP organ system studies ensure the safety of clinical participants in FiH trials. • Frontloading in SP facilitates lead candidate drug selection. • Emerging trends: integrating SP-Toxicological endpoints; combined core battery tests
Hamdam, Junnat; Sethu, Swaminathan; Smith, Trevor; Alfirevic, Ana; Alhaidari, Mohammad [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Atkinson, Jeffrey [Lorraine University Pharmacolor Consultants Nancy PCN (France); Ayala, Mimieveshiofuo; Box, Helen; Cross, Michael [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Delaunois, Annie [UCB Pharma (Belgium); Dermody, Ailsa; Govindappa, Karthik [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Guillon, Jean-Michel [Sanofi-aventis (France); Jenkins, Rosalind [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Kenna, Gerry [Astra-Zeneca (United Kingdom); Lemmer, Björn [Ruprecht-Karls-Universität Heidelberg (Germany); Meecham, Ken [Huntingdon Life Sciences (United Kingdom); Olayanju, Adedamola [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Pestel, Sabine [Boehringer-Ingelheim (Germany); Rothfuss, Andreas [Roche (Switzerland); and others
Safety pharmacology (SP) is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials. SP studies are described in the International Conference on Harmonisation (ICH) S7A and S7B guidelines. The core battery and supplemental SP studies evaluate effects of a new chemical entity (NCE) at both anticipated therapeutic and supra-therapeutic exposures on major organ systems, including cardiovascular, central nervous, respiratory, renal and gastrointestinal. This review outlines the current practices and emerging concepts in SP studies including frontloading, parallel assessment of core battery studies, use of non-standard species, biomarkers, and combining toxicology and SP assessments. Integration of the newer approaches to routine SP studies may significantly enhance the scope of SP by refining and providing mechanistic insight to potential adverse effects associated with test compounds. - Highlights: • SP — mandatory non-clinical risk assessments performed during drug development. • SP organ system studies ensure the safety of clinical participants in FiH trials. • Frontloading in SP facilitates lead candidate drug selection. • Emerging trends: integrating SP-Toxicological endpoints; combined core battery tests.
Beazley, David M
Python Essential Reference is the definitive reference guide to the Python programming language — the one authoritative handbook that reliably untangles and explains both the core Python language and the most essential parts of the Python library. Designed for the professional programmer, the book is concise, to the point, and highly accessible. It also includes detailed information on the Python library and many advanced subjects that is not available in either the official Python documentation or any other single reference source. Thoroughly updated to reflect the significant new programming language features and library modules that have been introduced in Python 2.6 and Python 3, the fourth edition of Python Essential Reference is the definitive guide for programmers who need to modernize existing Python code or who are planning an eventual migration to Python 3. Programmers starting a new Python project will find detailed coverage of contemporary Python programming idioms.
Zuckerman, Jane N; Leggat, Peter
This 1st edition of Essential Travel Medicine provides an excellent concise introduction to the specialty of Travel Medicine. This core text will enable health care practitioners particularly those new to the clinical practice of Travel Medicine, to gain a fundamental understanding of the diverse and complex issues which can potentially affect the health of the many millions of people who undertake international travel. Jane N Zuckerman is joined by Gary W Brunette from CDC and Peter A Leggat from Australia as Editors. Leading international specialists in their fields have contributed authoritative chapters reflecting current knowledge to facilitate best clinical practice in the different aspects of travel medicine. The aim of Essential Travel Medicine is to provide a comprehensive guide to Travel Medicine as well as a fundamental knowledge base to support international undergraduate and postgraduate specialty training programmes in the discipline of Travel Medicine. The 1st edition of Essential Travel ...
Full Text Available ... Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use and Other People Drug Use and Families Drug Use and Kids Drug Use and Unborn ...
Full Text Available ... Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, ... Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug Use and Kids ...
Full Text Available ... People Drug Use and Families Drug Use and Kids Drug Use and Unborn Children Drug Use and ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used ...
For students who just need to know the vital concepts of physics, whether as a refresher, for exam prep, or as a reference, Physics Essentials For Dummies is a must-have guide. Free of ramp-up and ancillary material, Physics Essentials For Dummies contains content focused on key topics only. It provides discrete explanations of critical concepts taught in an introductory physics course, from force and motion to momentum and kinetics. This guide is also a perfect reference for parents who need to review critical physics concepts as they help high school students with homework assignments, as we
Essentials of Computational Electromagnetics provides an in-depth introduction of the three main full-wave numerical methods in computational electromagnetics (CEM); namely, the method of moment (MoM), the finite element method (FEM), and the finite-difference time-domain (FDTD) method. Numerous monographs can be found addressing one of the above three methods. However, few give a broad general overview of essentials embodied in these methods, or were published too early to include recent advances. Furthermore, many existing monographs only present the final numerical results without specifyin
Full Text Available Background: Essential tremor (ET is one of the most common neurological disorders among adults, and is the most common of the many tremor disorders. It has classically been viewed as a benign monosymptomatic condition, yet over the past decade, a growing body of evidence indicates that ET is a progressive condition that is clinically heterogeneous, as it may be associated with a spectrum of clinical features, with both motor and non‐motor elements. In this review, I will describe the most significant emerging milestones in research which, when taken together, suggest that ET is a neurodegenerative condition.Methods: A PubMed search conducted in June 2014 crossing the terms “essential tremor” (ET and “neurodegenerative” yielded 122 entries, 20 of which included the term “neurodegenerative” in the article title. This was supplemented by articles in the author's files that pertained to this topic.Results/Discussion: There is an open and active dialogue in the medical community as to whether ET is a neurodegenerative disease, with considerable evidence in favor of this. Specifically, ET is a progressive disorder of aging associated with neuronal loss (reduction in Purkinje cells as well as other post‐mortem changes that occur in traditional neurodegenerative disorders. Along with this, advanced neuroimaging techniques are now demonstrating distinct structural changes, several of which are consistent with neuronal loss, in patients with ET. However, further longitudinal clinical and neuroimaging longitudinal studies to assess progression are required.
Sun, Benjamin C.; Costantino, Giorgio; Barbic, Franca; Bossi, Ilaria; Casazza, Giovanni; Dipaola, Franca; McDermott, Daniel; Quinn, James; Reed, Matthew; Sheldon, Robert S.; Solbiati, Monica; Thiruganasambandamoorthy, Venkatesh; Krahn, Andrew D.; Beach, Daniel; Bodemer, Nicolai; Brignole, Michele; Casagranda, Ivo; Duca, Piergiorgio; Falavigna, Greta; Ippoliti, Roberto; Montano, Nicola; Olshansky, Brian; Raj, Satish R.; Ruwald, Martin H.; Shen, Win-Kuang; Stiell, Ian; Ungar, Andrea; van Dijk, J. Gert; van Dijk, Nynke; Wieling, Wouter; Furlan, Raffaello
There is limited evidence to guide the emergency department (ED) evaluation and management of syncope. The First International Workshop on Syncope Risk Stratification in the Emergency Department identified key research questions and methodological standards essential to advancing the science of
AMADEI, A; LINSSEN, ABM; BERENDSEN, HJC
Analysis of extended molecular dynamics (MD) simulations of lysozyme in vacuo and in aqueous solution reveals that it is possible to separate the configurational space into two subspaces: (1) an ''essential'' subspace containing only a few degrees of freedom in which anharmonic motion occurs that
Bhuwan Raj Pandey
Full Text Available Introduction: Palatal myoclonus is a rare condition presenting with clicking sound in ear or muscle tremor in pharynx. There are two varieties: essential and symptomatic. Various treatment options exists ranging from watchful observation to botulinum toxin injection. We have not found any reported case of palatal myoclonus from our country. Here we present a case of essential palatal myoclonus managed with clonazepam. Case report: A young female presented in Ear Nose and Throat clinic with complain of auditory click and spontaneous rhythmic movement of throat muscles for eight months. On examination, there was involuntary, rhythmic contraction of bilateral soft-palate, uvula, and base of tongue. Neurological, eye, and peripheral examination were normal. A diagnosis of essential palatal myoclonus was made. It was managed successfully with clonazepam; patient was still on low dose clonazepam at the time of making this report. Conclusion: Essential palatal myoclonus can be clinically diagnosed and managed even in settings where MRI is not available or affordable.
This document presents the essential activities of the Areva Group, a world nuclear industry leader. This group proposes technological solutions to produce the nuclear energy and to transport the electric power. It develops connection systems for the telecommunication, the computers and the automotive industry. Key data on the program management, the sustainable development activities and the different divisions are provided. (A.L.B.)
Roeser, S.; Hillerbrand, R.; Sandin, P.; Peterson, M.B.
Risk has become one of the main topics in fields as diverse as engineering, medicine and economics, and it is also studied by social scientists, psychologists and legal scholars. This Springer Essentials version offers an overview of the in-depth handbook and highlights some of the main points
Julia Dutra Rossetto
Full Text Available The present study reports two cases of symptomatic essential trichomegaly. Trichomegaly may develop in various diseases, including anorexia nervosa, hypothyroidism, pregnancy, pretibial myxedema, systemic lupus erythematosus, vernal keratoconjunctivitis, and uveitis. The exact incidence trichomegaly is unknown, and the condition remains sporadically reported. Two cases of symptomatic trichomegaly without any associated systemic disorder are presented in this paper.
Desserud, K F; Veen, T; Søreide, K
Emergency general surgery in the elderly is a particular challenge to the surgeon in charge of their care. The aim was to review contemporary aspects of managing elderly patients needing emergency general surgery and possible alterations to their pathways of care. This was a narrative review based on a PubMed/MEDLINE literature search up until 15 September 2015 for publications relevant to emergency general surgery in the geriatric patient. The number of patients presenting as an emergency with a general surgical condition increases with age. Up to one-quarter of all emergency admissions to hospital may be for general surgical conditions. Elderly patients are a particular challenge owing to added co-morbidity, use of drugs and risk of poor outcome. Frailty is an important potential risk factor, but difficult to monitor or manage in the emergency setting. Risk scores are not available universally. Outcomes are usually severalfold worse than after elective surgery, in terms of both higher morbidity and increased mortality. A care bundle including early diagnosis, resuscitation and organ system monitoring may benefit the elderly in particular. Communication with the patient and relatives throughout the care pathway is essential, as indications for surgery, level of care and likely outcomes may evolve. Ethical issues should also be addressed at every step on the pathway of care. Emergency general surgery in the geriatric patient needs a tailored approach to improve outcomes and avoid futile care. Although some high-quality studies exist in related fields, the overall evidence base informing perioperative acute care for the elderly remains limited. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.
... The Marfan Foundation Marfan & Related Disorders What is Marfan Syndrome? What are Related Disorders? What are the Signs? ... Emergencies Lung Emergencies Surgeries Lung Emergencies People with Marfan syndrome can be at increased risk of sudden lung ...
Thukral, Inderpreet S.; Von Ehr, James; Walsh, Steven Thomas; Groen, Arend J.; van der Sijde, Peter; Adham, Khairul Akmaliah
Academics and practitioners alike have long understood the benefits, if not the risks, of both emerging markets and emerging technologies.Yet it is only recently that foresighted firms have embraced emerging technologies and emerging markets through entrepreneurial activity. Emerging technologies
Aims: This article reports on findings to emerge from a project examining YouTube "drug videos" in the light of an emerging literature on the relationship between YouTube and health education. The aim of this article is to describe the variety of discourses circulated by the "drug videos" available on YouTube and to consider…
Musselwhite, Laura W; Maciag, Karolina; Lankowski, Alex; Gretes, Michael C; Wellems, Thomas E; Tavera, Gloria; Goulding, Rebecca E; Guillen, Ethan
Universities Allied for Essential Medicines organized its first Neglected Diseases and Innovation Symposium to address expanding roles of public sector research institutions in innovation in research and development of biomedical technologies for treatment of diseases, particularly neglected tropical diseases. Universities and other public research institutions are increasingly integrated into the pharmaceutical innovation system. Academic entities now routinely undertake robust high-throughput screening and medicinal chemistry research programs to identify lead compounds for small molecule drugs and novel drug targets. Furthermore, product development partnerships are emerging between academic institutions, non-profit entities, and biotechnology and pharmaceutical companies to create diagnostics, therapies, and vaccines for diseases of the poor. With not for profit mission statements, open access publishing standards, open source platforms for data sharing and collaboration, and a shift in focus to more translational research, universities and other public research institutions are well-placed to accelerate development of medical technologies, particularly for neglected tropical diseases.
Laing, R O; McGoldrick, K M
Access to tuberculosis drugs depends on multiple factors. Selection of a standard list of TB drugs to procure is the first step. This paper reviews the advantages and disadvantages of procuring and using fixed-dose combination (FDC) products for both the intensive and continuation phases of treatment. The major advantages are to prevent the emergence of resistance, to simplify logistic management and to reduce costs. The major disadvantage is the need for the manufacturers to assure the quality of these FDCs by bioavailability testing. The paper reports on the inclusion of second-line TB drugs in the 1999 WHO Essential Drug List (EDL). The need to ensure that these drugs are used within established DOTS-Plus programs is stressed. The price of TB drugs is determined by many factors, including producer prices, local taxes and duties as well as mark-ups and fees. TB drug prices for both the public and private sectors from industrialized and developing countries are reported. Price trends over time are also reported. The key findings of this study are that TB drug prices have generally declined in developing countries while they have increased in developed countries, both for the public and private sectors. Prices vary between countries, with the US paying as much as 95 times the price paid in a specific developing country. The prices of public sector first-line TB drugs vary little between countries, although differences do exist due to the procurement methods used. The price of tuberculin, a diagnostic agent, has increased dramatically in the US, with substantial inter-country variations in price. The paper suggests that further research is necessary to identify the reasons for the price disparities and changes over time, and suggests methods which can be used by National Tuberculosis Programme managers to ensure availability of quality assured TB drugs at low prices.
Since its publication, Essentials of Artificial Intelligence has beenadopted at numerous universities and colleges offering introductory AIcourses at the graduate and undergraduate levels. Based on the author'scourse at Stanford University, the book is an integrated, cohesiveintroduction to the field. The author has a fresh, entertaining writingstyle that combines clear presentations with humor and AI anecdotes. At thesame time, as an active AI researcher, he presents the materialauthoritatively and with insight that reflects a contemporary, first hand
If you are an experienced system administrator and know how to manage servers and set up web environments but now want to explore Moodle, this book is perfect for you. You'll get to grips with the basics and learn to manage Moodle quickly, focusing on essential tasks. Having prior knowledge of virtual learning environments would be beneficial, but is not mandatory to make the most of this book.
Holtzman DJ, et al. Quality of root-end preparations using ultrasonic and rotary instrumentation in cadavers. J Endod 2000;26:281. 39. Peters CI...00-00-2010 to 00-00-2010 4. TITLE AND SUBTITLE Essentials of Endodontic Microsurgery 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT... Endodontic Program,Harvard School of Dental Medicine,Boston,MA 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND
Persse, James R
Process Improvement Essentials combines the foundation needed to understand process improvement theory with the best practices to help individuals implement process improvement initiatives in their organization. The three leading programs: ISO 9001:2000, CMMI, and Six Sigma--amidst the buzz and hype--tend to get lumped together under a common label. This book delivers a combined guide to all three programs, compares their applicability, and then sets the foundation for further exploration.
IPv6 Essentials, Second Edition provides a succinct, in-depth tour of all the new features and functions in IPv6. It guides you through everything you need to know to get started, including how to configure IPv6 on hosts and routers and which applications currently support IPv6. Aimed at system and network administrators, engineers, network designers, and IT managers, this book will help you understand, plan for, design, and integrate IPv6 into your current IPv4 infrastructure
Android Application Security Essentials is packed with examples, screenshots, illustrations, and real world use cases to secure your apps the right way.If you are looking for guidance and detailed instructions on how to secure app data, then this book is for you. Developers, architects, managers, and technologists who wish to enhance their knowledge of Android security will find this book interesting. Some prior knowledge of development on the Android stack is desirable but not required.
A step-by-step and interactive approach explaining the Rake essentials along with code examples and advanced features. If you are a developer who is acquainted with the Ruby language and want to speed up writing the code concerned with files, then this book is for you. To start reading this book, basic Ruby knowledge is required; however, a huge amount of experience with the language is not necessary.
Heuett, Nubia V; Batchu, Sudha Rani; Gardinali, Piero R
A QExactive Orbitrap was used for the identification of phase I and II transformation products (TPs) of illicit drugs in raw sewage influents. Two operating modes (targeted MS(2) and Data-dependent screening) were used for data acquisition. Even though, data-dependent scan is a faster route towards the potential identification of metabolites, it suffered from its limitation to provide enough data points across the chromatographic peak during the MS(2) cycle in contrast to targeted MS(2). Therefore, the later technique was implemented as the method of choice in this study for the positive confirmation and quantitation of TPs (n=54). The vast majority of the identified TPs were products of phase I transformation reactions, with the latter being more prevalent in the nature. Estimated mole fractions showed that for a large number of the analytes, TPs must also be monitored in order to fully understand their environmental fate and calculate potential consumption. Copyright © 2014 Elsevier B.V. All rights reserved.
Derrida, in the interview Rhetoric of Drugs (1993), following on from the explication of the notion of pharmakon (both poison and beneficial drug, at the same time), outlines a possible ï¿½theoryï¿½ of drugs and addiction. It has several key features:\\ud ï¿½ there are no drugs in nature: the definition of ï¿½drugï¿½ is an institutionalised one\\ud ï¿½ the concept of drugs is non-scientific, non-positive\\ud ï¿½ drugs are a parasitism ï¿½at once accidental and essentialï¿½; and are thus a topic ...
Porter, Danielle P; Daeumer, Martin; Thielen, Alexander; Chang, Silvia; Martin, Ross; Cohen, Cal; Miller, Michael D; White, Kirsten L
At Week 96 of the Single-Tablet Regimen (STaR) study, more treatment-naïve subjects that received rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF) developed resistance mutations compared to those treated with efavirenz (EFV)/FTC/TDF by population sequencing. Furthermore, more RPV/FTC/TDF-treated subjects with baseline HIV-1 RNA >100,000 copies/mL developed resistance compared to subjects with baseline HIV-1 RNA ≤100,000 copies/mL. Here, deep sequencing was utilized to assess the presence of pre-existing low-frequency variants in subjects with and without resistance development in the STaR study. Deep sequencing (Illumina MiSeq) was performed on baseline and virologic failure samples for all subjects analyzed for resistance by population sequencing during the clinical study (n = 33), as well as baseline samples from control subjects with virologic response (n = 118). Primary NRTI or NNRTI drug resistance mutations present at low frequency (≥2% to 20%) were detected in 6.6% of baseline samples by deep sequencing, all of which occurred in control subjects. Deep sequencing results were generally consistent with population sequencing but detected additional primary NNRTI and NRTI resistance mutations at virologic failure in seven samples. HIV-1 drug resistance mutations emerging while on RPV/FTC/TDF or EFV/FTC/TDF treatment were not present at low frequency at baseline in the STaR study.
Danielle P. Porter
Full Text Available At Week 96 of the Single-Tablet Regimen (STaR study, more treatment-naïve subjects that received rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF developed resistance mutations compared to those treated with efavirenz (EFV/FTC/TDF by population sequencing. Furthermore, more RPV/FTC/TDF-treated subjects with baseline HIV-1 RNA >100,000 copies/mL developed resistance compared to subjects with baseline HIV-1 RNA ≤100,000 copies/mL. Here, deep sequencing was utilized to assess the presence of pre-existing low-frequency variants in subjects with and without resistance development in the STaR study. Deep sequencing (Illumina MiSeq was performed on baseline and virologic failure samples for all subjects analyzed for resistance by population sequencing during the clinical study (n = 33, as well as baseline samples from control subjects with virologic response (n = 118. Primary NRTI or NNRTI drug resistance mutations present at low frequency (≥2% to 20% were detected in 6.6% of baseline samples by deep sequencing, all of which occurred in control subjects. Deep sequencing results were generally consistent with population sequencing but detected additional primary NNRTI and NRTI resistance mutations at virologic failure in seven samples. HIV-1 drug resistance mutations emerging while on RPV/FTC/TDF or EFV/FTC/TDF treatment were not present at low frequency at baseline in the STaR study.
Ivanov, Sergey; Semin, Maxim; Lagunin, Alexey; Filimonov, Dmitry; Poroikov, Vladimir
Drug-induced liver injury (DILI) is the leading cause of acute liver failure as well as one of the major reasons for drug withdrawal from clinical trials and the market. Elucidation of molecular interactions associated with DILI may help to detect potentially hazardous pharmacological agents at the early stages of drug development. The purpose of our study is to investigate which interactions with specific human protein targets may cause DILI. Prediction of interactions with 1534 human proteins was performed for the dataset with information about 699 drugs, which were divided into three categories of DILI: severe (178 drugs), moderate (310 drugs) and without DILI (211 drugs). Based on the comparison of drug-target interactions predicted for different drugs' categories and interpretation of those results using clustering, Gene Ontology, pathway and gene expression analysis, we identified 61 protein targets associated with DILI. Most of the revealed proteins were linked with hepatocytes' death caused by disruption of vital cellular processes, as well as the emergence of inflammation in the liver. It was found that interaction of a drug with the identified targets is the essential molecular mechanism of the severe DILI for the most of the considered pharmaceuticals. Thus, pharmaceutical agents interacting with many of the identified targets may be considered as candidates for filtering out at the early stages of drug research. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Schaefer-Prokop, Cornelia; Eisenhuber, Edith
There is an ever increasing number of drugs that can cause lung disease. Imaging plays an important role in the diagnosis, since the clinical symptoms are mostly nonspecific. Various HRCT patterns can be correlated - though with overlaps - to lung changes caused by certain groups of drugs. Alternative diagnosis such as infection, edema or underlying lung disease has to be excluded by clinical-radiological means. Herefore is profound knowledge of the correlations of drug effects and imaging findings essential. History of drug exposure, suitable radiological findings and response to treatment (corticosteroids and stop of medication) mostly provide the base for the diagnosis. (orig.)
Full Text Available ... Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used Drugs in the Past Drug Use ... Videos Information About Drugs Alcohol ...
... Loss of consciousness Other conditions resulting from drug allergy Less common drug allergy reactions occur days or ... you take the drug. Drugs commonly linked to allergies Although any drug can cause an allergic reaction, ...
This chapter explores the use of mass spectrometry and its application to emerging contaminants (ECs) in the environment; such classes of compounds as organometallics, pharmaceuticals/drugs, nanomaterials, and dispersants (surfactants). Table 1 shows the variety of ECs that are...
Staudacher, Alexander H; Brown, Michael P
Antibody drug conjugates (ADCs) employ the exquisite specificity of tumour-specific monoclonal antibodies (mAb) for the targeted delivery of highly potent cytotoxic drugs to the tumour site. The chemistry of the linker, which connects the drug to the mAb, determines how and when the drug is released from the mAb. This, as well as the chemistry of the drug, can dictate whether the drug can diffuse into surrounding cells, resulting in 'bystander killing'. Initially, any bystander killing mechanism of action of an ADC was understood to involve an essential sequence of steps beginning with surface antigen targeting, internalisation, intracellular linker cleavage, drug release, and diffusion of drug away from the targeted cell. However, recent studies indicate that, depending on the linker and drug combination, this mechanism may not be essential and ADCs can be cleaved extracellularly or via other mechanisms. In this minireview, we will examine the role of bystander killing by ADCs and explore the emerging evidence of how this can occur independently of internalisation.
Sakkas, Hercules; Gousia, Panagiota; Economou, Vangelis; Sakkas, Vassilios; Petsios, Stefanos; Papadopoulou, Chrissanthy
The emergence of drug-resistant pathogens has drawn attention on medicinal plants for potential antimicrobial properties. The objective of the present study was the investigation of the antimicrobial activity of five plant essential oils on multidrug resistant Gram-negative bacteria. Basil, chamomile blue, origanum, thyme, and tea tree oil were tested against clinical isolates of Acinetobacter baumannii (n = 6), Escherichia coli (n = 4), Klebsiella pneumoniae (n = 7), and Pseudomonas aeruginosa (n = 5) using the broth macrodilution method. The tested essential oils produced variable antibacterial effect, while Chamomile blue oil demonstrated no antibacterial activity. Origanum, Thyme, and Basil oils were ineffective on P. aeruginosa isolates. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration values ranged from 0.12% to 1.50% (v/v) for tea tree oil, 0.25-4% (v/v) for origanum and thyme oil, 0.50% to >4% for basil oil and >4% for chamomile blue oil. Compared to literature data on reference strains, the reported MIC values were different by 2SD, denoting less successful antimicrobial activity against multidrug resistant isolates. The antimicrobial activities of the essential oils are influenced by the strain origin (wild, reference, drug sensitive, or resistant) and it should be taken into consideration whenever investigating the plants' potential for developing new antimicrobials.
Sarkar, N N
The objective of our study was the evaluation and elucidation of levonorgestrel (LNG) as emergency contraception (EC) administered through oral and vaginal routes. Data regarding post-coital oral and peri-coital vaginal application of LNG were extracted from the literature through MEDLINE database service for years 2001-2010. It was found that a single dose of 1.5 mg LNG or two doses of 0.75 mg LNG 12 h apart were used for EC. Currently, LNG is also on trial for vaginal application as EC in Carraguard gel for 'dual protection'. The oral or vaginal dose of 1.5 mg LNG resulted in peak plasma concentration, C(max) 19.2 or 3.21 ng/ml, with shorter time, T(max) 1.4 or 6.6 h, and greater AUC, 152.7 or 52.5 ng.h/ml, with shorter half-life, 25 or 32 h, respectively. LNG EC inhibited mid-cycle LH surge and delayed or prevented ovulation when administered before ovulation. Mechanism of action of LNG EC appeared to inhibit or delay ovulation. The risk of pregnancy was 4.12%. A single dose of 1.5 mg LNG could reduce the pregnancy rate to 0.7%. Occurrence of ectopic pregnancy following failure of LNG EC was reported. This EC caused no serious adverse effects but was associated with menstrual disturbance. Although widely acceptable, the cost and short-supply to rural areas pose a barrier to access EC for the poor and rural-dwellers, respectively. It was concluded that unlike post-coital oral administration, peri-coital vaginal application of 1.5 mg LNG needs further study to be an alternative option for women to use it for prevention of pregnancy.
Ellenberg, Susan S; Keusch, Gerald T; Babiker, Abdel G
Randomized clinical trials are the most reliable approaches to evaluating the effects of new treatments and vaccines. During the 2014-15 West African Ebola epidemic, many argued that such trials were neither ethical nor feasible in an environment of limited health infrastructure and severe disease...
1) Introduction: Summary of system technology and reactor protection equipment. 2) Definitions. 3) LOCA: a) blowdown and refilling phase; b) jet and reaction forces; c) flow and heat transfer behavior in the core; d) behavior of the heater rods; e) core melting. 4) Protection against and during LOCA: a) general measures; b) break of a primary coolant pipe; c) break of a small pipe; d) break of a secondary pipe. (orig.) [de
... foundations, emerging technologies and innovations in regulatory science, as well as the current quality and... strategies, while industry professionals from some of today's leading pharmaceutical companies present case.... Drug Safety. Emerging Active Pharmaceutical Ingredients (API) Regulations. Investigations. Emerging API...
Ramina, Ricardo; Pontifical Catholic Univ. of Parana, Curitiba; Pires Aguiar, Paulo Henrique; Sao Paulo Univ.; Hospital Santa Paula, Sao Paulo; Tatagiba, Marcos
'Samii's Essentials in Neurosurgery' contains selected papers written by internationally recognized contributors who were trained by Professor Madjid Samii in Hannover, Germany. The main topics deal with cutting-edge technology in neurosurgery, skull-base surgery, and specific peripheral nerve, spine, and vascular surgeries. The texts and a wealth of illustrations review and reinforce guidelines on the diagnosis and management of situations that readers are likely to encounter in everyday practice. This book will be of great interest to neurosurgeons, neurologists, ENT surgeons, neuroradiologists, and neurophysiotherapists. (orig.)
Just the critical concepts you need to score high in geometry This practical, friendly guide focuses on critical concepts taught in a typical geometry course, from the properties of triangles, parallelograms, circles, and cylinders, to the skills and strategies you need to write geometry proofs. Geometry Essentials For Dummies is perfect for cramming or doing homework, or as a reference for parents helping kids study for exams. Get down to the basics - get a handle on the basics of geometry, from lines, segments, and angles, to vertices, altitudes, and diagonals Conque
ForewordPrefaceComputing ParadigmsLearning ObjectivesPreambleHigh-Performance ComputingParallel ComputingDistributed ComputingCluster ComputingGrid ComputingCloud ComputingBiocomputingMobile ComputingQuantum ComputingOptical ComputingNanocomputingNetwork ComputingSummaryReview PointsReview QuestionsFurther ReadingCloud Computing FundamentalsLearning ObjectivesPreambleMotivation for Cloud ComputingThe Need for Cloud ComputingDefining Cloud ComputingNIST Definition of Cloud ComputingCloud Computing Is a ServiceCloud Computing Is a Platform5-4-3 Principles of Cloud computingFive Essential Charact
The premiere book on getting started with Maya 2014 Whether you're just beginning, or migrating from another 3D application, this step-by-step guide is what you need to get a good working knowledge of Autodesk Maya 2014. Beautifully illustrated with full-color examples and screenshots, Autodesk Maya 2014 Essentials explains the basics of Maya as well as modeling, texturing, animating, setting a scene, and creating visual effects. You'll absorb important concepts and techniques, and learn how to confidently use Maya tools the way professionals do. Each chapter includes fun and cha
O'Donnell, Peter J
Essential Dynamics & Relativity provides students with an introduction to the core aspects of dynamics and special relativity. The author reiterates important ideas and terms throughout and covers concepts that are often missing from other textbooks at this level. He also places each topic within the wider constructs of the theory, without jumping from topic to topic to illustrate a point.The first section of the book focuses on dynamics, discussing the basic aspects of single particle motion and analyzing the motion of multi-particle systems. The book also explains the dynamical behavior of b
The essential fundamentals of 3D animation for aspiring 3D artists 3D is everywhere--video games, movie and television special effects, mobile devices, etc. Many aspiring artists and animators have grown up with 3D and computers, and naturally gravitate to this field as their area of interest. Bringing a blend of studio and classroom experience to offer you thorough coverage of the 3D animation industry, this must-have book shows you what it takes to create compelling and realistic 3D imagery. Serves as the first step to understanding the language of 3D and computer graphics (CG)Covers 3D anim
Twisted Network Programming Essentials from O'Reilly is a task-oriented look at this new open source, Python-based technology. The book begins with recommendations for various plug-ins and add-ons to enhance the basic package as installed. It then details Twisted's collection simple network protocols, and helper utilities. The book also includes projects that let you try out the Twisted framework for yourself. For example, you'll find examples of using Twisted to build web services applications using the REST architecture, using XML-RPC, and using SOAP. Written for developers who want to s
There are few scientists of the twentieth century whose life's work has created more excitement and controversy than that of physicist David Bohm (1917-1992). For the first time in a single volume, The Essential David Bohm offers a comprehensive overview of Bohm's original works from a non-technical perspective. Including three chapters of previously unpublished material, and a forward by the Dalai Lama, each reading has been selected to highlight some aspect of the implicate order process, and to provide an introduction to one of the most provocative thinkers of our time.
Windows security concepts and technologies for IT beginners IT security can be a complex topic, especially for those new to the field of IT. This full-color book, with a focus on the Microsoft Technology Associate (MTA) program, offers a clear and easy-to-understand approach to Windows security risks and attacks for newcomers to the world of IT. By paring down to just the essentials, beginners gain a solid foundation of security concepts upon which more advanced topics and technologies can be built. This straightforward guide begins each chapter by laying out a list of topics to be discussed,
The core concepts and technologies of Windows networking Networking can be a complex topic, especially for those new to the field of IT. This focused, full-color book takes a unique approach to teaching Windows networking to beginners by stripping down a network to its bare basics, thereby making each topic clear and easy to understand. Focusing on the new Microsoft Technology Associate (MTA) program, this book pares down to just the essentials, showing beginners how to gain a solid foundation for understanding networking concepts upon which more advanced topics and technologies can be built.
An engaging approach for anyone beginning a career in networking As the world leader of networking products and services, Cisco products are constantly growing in demand. Yet, few books are aimed at those who are beginning a career in IT--until now. Cisco Networking Essentials provides a solid foundation on the Cisco networking products and services with thorough coverage of fundamental networking concepts. Author Troy McMillan applies his years of classroom instruction to effectively present high-level topics in easy-to-understand terms for beginners. With this indispensable full-color resour
Lawless, Laura K
Just the core concepts you need to write and speak French correctly If you have some knowledge of French and want to polish your skills, French Essentials For Dummies focuses on just the core concepts you need to communicate effectively. From conjugating verbs to understanding tenses, this easy-to-follow guide lets you skip the suffering and score high at exam time. French 101 - get the lowdown on the basics, from expressing dates and times to identifying parts of speech Gender matters - see how a noun's gender determines the articles, adjectives, and pronouns y
Start a career in networking Cisco Networking Essentials, 2nd Edition provides the latest for those beginning a career in networking. This book provides the fundamentals of networking and leads you through the concepts, processes, and skills you need to master fundamental networking concepts. Thinking of taking the CCENT Cisco Certified Entry Networking Technician ICND1 Exam 100-101? This book has you covered! With coverage of important topics and objectives, each chapter outlines main points and provides clear, engaging discussion that will give you a sound understanding of core topics and c
This book is a quick and concise introduction to RabbitMQ. Follow the unique case study of Clever Coney Media as they progressively discover how to fully utilize RabbitMQ, containing clever examples and detailed explanations.Whether you are someone who develops enterprise messaging products professionally or a hobbyist who is already familiar with open source Message Queuing software and you are looking for a new challenge, then this is the book for you. Although you should be familiar with Java, Ruby, and Python to get the most out of the examples, RabbitMQ Essentials will give you the push y
... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Definition of emergency situation. 290.10 Section...) DRUGS: GENERAL CONTROLLED DRUGS General Provisions § 290.10 Definition of emergency situation. For the... Controlled Substances Act, the term emergency situation means those situations in which the prescribing...
Roberta Simone Andreazza
Full Text Available Objective: To assess the frequency and types of drug-related problems (DRPs in patients seeking emergency care in a teaching hospital in southern Brazil and to identify the possible causes and drugs involved in these problems. Method: A cross-sectional study was performed, using a structured questionnaire for data collection. Multivariate logistic regression was used to control for possible confounding factors and to establish an independent association between the presence of DRPs and the amount of medication, patient's age and their educational level. Results: A total of 350 patients were interviewed. The frequency of DRPs was 31.6%. Quantitative ineffectiveness was observed in 30.9% of DRPs and the main cause of the DRP was an inadequate dosing regimen. Sixty-six DRPs (53.7% were caused by the health system or the health professionals. Factors independently influencing the development of DRPs were educational level and the number of drugs being taken. Conclusions: Our data suggest that one-third of the patients attending the emergency room of our hospital had a drug-related problem, highlighting the importance of considering drugs as a possible cause of health problems and the need for their more rational use.Objetivo: Evaluar la frecuencia y el tipo de problemas relacionados con medicamentos que presentan los pacientes que acuden al servicio de urgencias en un hospital universitario del sur de Brasil, e identificar las posibles causas y los fármacos involucrados. Método: La investigación siguió el modelo de estudio transversal, con una encuesta estructurada para la recogida de los datos. Se empleó el análisis de regresión logística múltiple para controlar posibles factores de confusión y establecer una asociación independiente entre la presencia de problemas relacionados con medicamentos y el número de éstos, la edad y el nivel educativo. Resultados: Se entrevistaron 350 pacientes y la frecuencia de problemas relacionados con
Martínez de Victoria, Emilio
Calcium (Ca) is the most abundant mineral element in our body. It accounts for about 2% of body weight. The functions of calcium are: a) functions skeletal and b) regulatory functions. Bone consists of a protein matrix that mineralizes mainly with calcium (the most abundant), phosphate and magnesium, for it is essential an adequate dietary intake of Ca, phosphorus and vitamin D. The ionic Ca (Ca2+) is essential to maintain and / or perform different specialized functions of, virtually, all body cells cellular. Because of its important functions Ca2+ must be closely regulated, keeping plasma concentrations within narrow ranges. For this reason there is an accurate response against hypocalcemia or hypercalcemia in which the parathormone, calcitriol, calcitonin and vitamin K are involved. Ca intakes in the Spanish population are low in a significant percentage of the older adult’s population, especially in women. The main source of Ca in the diet is milk and milk derivatives. Green leafy vegetables, fruits and legumes can be important sources of Ca in a Mediterranean dietary pattern. The bioavailability of dietary Ca depends on physiological and dietary factors. Physiological include age, physiological status (gestation and lactation) Ca and vitamin D status and disease. Several studies relate Ca intake in the diet and various diseases, such as osteoporosis, cancer, cardiovascular disease and obesity.
Molecular Diversity of HIV-1 among People Who Inject Drugs in Kuala Lumpur, Malaysia: Massive Expansion of Circulating Recombinant Form (CRF) 33_01B and Emergence of Multiple Unique Recombinant Clusters
Chow, Wei Zhen; Ng, Kim Tien; Yong, Yean Kong; Azmel, Azureen; Takebe, Yutaka; Al-Darraji, Haider Abdulrazzaq Abed; Kamarulzaman, Adeeba; Tee, Kok Keng
Since the discovery of HIV-1 circulating recombinant form (CRF) 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B′ of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID) however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B′ (11%) and CRF01_AE (5%)] and CRF01_AE/B′ unique recombinants (13%) were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B′ recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers) and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the
Molecular diversity of HIV-1 among people who inject drugs in Kuala Lumpur, Malaysia: massive expansion of circulating recombinant form (CRF) 33_01B and emergence of multiple unique recombinant clusters.
Chow, Wei Zhen; Ong, Lai Yee; Razak, Siti Humaira; Lee, Yeat Mei; Ng, Kim Tien; Yong, Yean Kong; Azmel, Azureen; Takebe, Yutaka; Al-Darraji, Haider Abdulrazzaq Abed; Kamarulzaman, Adeeba; Tee, Kok Keng
Since the discovery of HIV-1 circulating recombinant form (CRF) 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B' of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID) however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B' (11%) and CRF01_AE (5%)] and CRF01_AE/B' unique recombinants (13%) were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B' recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers) and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the escalating
Molecular diversity of HIV-1 among people who inject drugs in Kuala Lumpur, Malaysia: massive expansion of circulating recombinant form (CRF 33_01B and emergence of multiple unique recombinant clusters.
Wei Zhen Chow
Full Text Available Since the discovery of HIV-1 circulating recombinant form (CRF 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B' of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B' (11% and CRF01_AE (5%] and CRF01_AE/B' unique recombinants (13% were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B' recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the
Saab, Antoine M; Gambari, Roberto; Sacchetti, Gianni; Guerrini, Alessandra; Lampronti, Ilaria; Tacchini, Massimo; El Samrani, Antoine; Medawar, Samir; Makhlouf, Hassane; Tannoury, Mona; Abboud, Jihad; Diab-Assaf, Mona; Kijjoa, Anake; Tundis, Rosa; Aoun, Jawad; Efferth, Thomas
Natural products frequently exert pharmacological activities. The present review gives an overview of the ethnobotany, phytochemistry and pharmacology of the Cedrus genus, e.g. cytotoxic, spasmolytic immunomodulatory, antiallergic, anti-inflammatory and analgesic activities. Cancer patients frequently seek remedies from traditional medicinal plants that are believed to exert less side effects than conventional therapy with synthetic drugs. A long-lasting goal of anti-cancer and anti-microbial therapy research is to find compounds with reduced side effects compared to currently approved drugs. In this respect, Cedrus species might be of interest. The essential oil isolated from Cedrus libani leaves may bear potential for drug development due to its high concentrations of germacrene D and β-caryophyllene. The essential oils from Cedrus species also show bioactivity against bacteria and viruses. More preclinical analyses (e.g. in vivo experiments) as well as clinical trials are required to evaluate the potential of essential oils from Cedrus species for drug development.
Serra, Elisa; Hidalgo-Bastida, Lilia Araida; Verran, Joanna; Williams, David; Malic, Sladjana
Management of oral candidosis, most frequently caused by Candida albicans , is limited due to the relatively low number of antifungal drugs and the emergence of antifungal tolerance. In this study, the antifungal activity of a range of commercial essential oils, two terpenes, chlorhexidine and triclosan was evaluated against C. albicans in planktonic and biofilm form. In addition, cytotoxicity of the most promising compounds was assessed using murine fibroblasts and expressed as half maximal inhibitory concentrations (IC50). Antifungal activity was determined using a broth microdilution assay. The minimum inhibitory concentration (MIC) was established against planktonic cells cultured in a range of concentrations of the test agents. The minimal biofilm eradication concentration (MBEC) was determined by measuring re-growth of cells after pre-formed biofilm was treated for 24 h with the test agents. All tested commercial essential oils demonstrated anticandidal activity (MICs from 0.06% ( v / v ) to 0.4% ( v / v )) against planktonic cultures, with a noticeable increase in resistance exhibited by biofilms (MBECs > 1.5% ( v / v )). The IC50s of the commercial essential oils were lower than the MICs, while a one hour application of chlorhexidine was not cytotoxic at concentrations lower than the MIC. In conclusion, the tested commercial essential oils exhibit potential as therapeutic agents against C. albicans , although host cell cytotoxicity is a consideration when developing these new treatments.
Federal Laboratory Consortium — The Center for Drug Evaluation and Research(CDER) performs an essential public health task by making sure that safe and effective drugs are available to improve the...
Hamdam, Junnat; Sethu, Swaminathan; Smith, Trevor; Alfirevic, Ana; Alhaidari, Mohammad; Atkinson, Jeffrey; Ayala, Mimieveshiofuo; Box, Helen; Cross, Michael; Delaunois, Annie; Dermody, Ailsa; Govindappa, Karthik; Guillon, Jean-Michel; Jenkins, Rosalind; Kenna, Gerry; Lemmer, Björn; Meecham, Ken; Olayanju, Adedamola; Pestel, Sabine; Rothfuss, Andreas; Sidaway, James; Sison-Young, Rowena; Smith, Emma; Stebbings, Richard; Tingle, Yulia; Valentin, Jean-Pierre; Williams, Awel; Williams, Dominic; Park, Kevin; Goldring, Christopher
Safety pharmacology (SP) is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials. SP studies are described in the International Conference on Harmonisation (ICH) S7A and S7B guidelines. The core battery and supplemental SP studies evaluate effects of a new chemical entity (NCE) at both anticipated therapeutic and supra-therapeutic exposures on major organ systems, including cardiovascular, central nervous, respiratory, renal and gastrointestinal. This review outlines the current practices and emerging concepts in SP studies including frontloading, parallel assessment of core battery studies, use of non-standard species, biomarkers, and combining toxicology and SP assessments. Integration of the newer approaches to routine SP studies may significantly enhance the scope of SP by refining and providing mechanistic insight to potential adverse effects associated with test compounds. Copyright © 2013 Elsevier Inc. All rights reserved.
Achan, Jane; Mwesigwa, Julia; Edwin, Chinagozi Precious; D'alessandro, Umberto
Antimalarial drugs are essential weapons to fight malaria and have been used effectively since the 17 th century. However, P.falciparum resistance has been reported to almost all available antimalarial drugs, including artemisinin derivatives, raising concerns that this could jeopardize malaria elimination. Areas covered: In this article, we present a historical perspective of antimalarial drug resistance, review current evidence of resistance to available antimalarial drugs and discuss possible mitigating strategies to address this challenge. Expert commentary: The historical approach to drug resistance has been to change the national treatment policy to an alternative treatment. However, alternatives to artemisinin-based combination treatment are currently extremely limited. Innovative approaches utilizing available schizonticidal drugs such as triple combination therapies or multiple first line treatments could delay the emergence and spread of drug resistance. Transmission blocking drugs like primaquine may play a key role if given to a substantial proportion of malaria infected persons. Deploying antimalarial medicines in mass drug administration or mass screening and treatment campaigns could also contribute to containment efforts by eliminating resistant parasites in some settings. Ultimately, response to drug resistance should also include further investment in the development of new antimalarial drugs.
Johnson, Michael L
The use of computers and computational methods has become ubiquitous in biological and biomedical research. During the last 2 decades most basic algorithms have not changed, but what has is the huge increase in computer speed and ease of use, along with the corresponding orders of magnitude decrease in cost. A general perception exists that the only applications of computers and computer methods in biological and biomedical research are either basic statistical analysis or the searching of DNA sequence data bases. While these are important applications they only scratch the surface of the current and potential applications of computers and computer methods in biomedical research. The various chapters within this volume include a wide variety of applications that extend far beyond this limited perception. As part of the Reliable Lab Solutions series, Essential Numerical Computer Methods brings together chapters from volumes 210, 240, 321, 383, 384, 454, and 467 of Methods in Enzymology. These chapters provide ...
In DSP Architecture Design Essentials, authors Dejan Marković and Robert W. Brodersen cover a key subject for the successful realization of DSP algorithms for communications, multimedia, and healthcare applications. The book addresses the need for DSP architecture design that maps advanced DSP algorithms to hardware in the most power- and area-efficient way. The key feature of this text is a design methodology based on a high-level design model that leads to hardware implementation with minimum power and area. The methodology includes algorithm-level considerations such as automated word-length reduction and intrinsic data properties that can be leveraged to reduce hardware complexity. From a high-level data-flow graph model, an architecture exploration methodology based on linear programming is used to create an array of architectural solutions tailored to the underlying hardware technology. The book is supplemented with online material: bibliography, design examples, CAD tutorials and custom software.
Essential French Grammar is an innovative reference grammar and workbook for intermediate and advanced undergraduate students of French (CEFR levels B2 to C1). Its clear explanations of grammar are supported by contemporary examples and lively cartoon drawings. Each chapter contains: * real-life language examples in French, with English translations * a 'key points' box and tables that summarise grammar concepts * a variety of exercises to reinforce learning * a contemporary primary source or literary extract to illustrate grammar in context. To aid your understanding, this book also contains a glossary of grammatical terms in French and English, useful verb tables and a key to the exercises. Together, these features all help you to grasp complex points of grammar and develop your French language skills.
This book provides a rigorous introduction to the techniques and results of real analysis, metric spaces and multivariate differentiation, suitable for undergraduate courses. Starting from the very foundations of analysis, it offers a complete first course in real analysis, including topics rarely found in such detail in an undergraduate textbook such as the construction of non-analytic smooth functions, applications of the Euler-Maclaurin formula to estimates, and fractal geometry. Drawing on the author’s extensive teaching and research experience, the exposition is guided by carefully chosen examples and counter-examples, with the emphasis placed on the key ideas underlying the theory. Much of the content is informed by its applicability: Fourier analysis is developed to the point where it can be rigorously applied to partial differential equations or computation, and the theory of metric spaces includes applications to ordinary differential equations and fractals. Essential Real Analysis will appeal t...
Chambers, D W
This is an introduction to the major concepts in total quality management, a loose collection of management approaches that focus on continuous improvement of processes, guided by routine data collection and adjustment of the processes. Customer focus and involvement of all members of an organization are also characteristics commonly found in TQM. The seventy-five-year history of the movement is sketched from its beginning in statistical work on quality assurance through the many improvements and redefinitions added by American and Japanese thinkers. Essential concepts covered include: control cycles, focus on the process rather than the defects, the GEAR model, importance of the customer, upstream quality, just-in-time, kaizen, and service quality.
China looks to strategically important emerging industries for innovation-driven economic growthc hina will soon announce a decision to rev up seven strategically impor- tant emerging industries,said the National
Peterson, Eric; Owens, S Michael; Henry, Ralph L
Drug abuse continues to be a major national and worldwide problem, and effective treatment strategies are badly needed. Antibodies are promising therapies for the treatment of medical problems caused by drug abuse, with several candidates in preclinical and early clinical trials. Monoclonal antibodies can be designed that have customized affinity and specificity against drugs of abuse, and because antibodies can be designed in various forms, in vivo pharmacokinetic characteristics can be tailored to suit specific clinical applications (eg, long-acting for relapse prevention, or short-acting for overdose). Passive immunization with antibodies against drugs of abuse has several advantages over active immunization, but because large doses of monoclonal antibodies may be needed for each patient, efficient antibody production technology is essential. In this minireview we discuss some of the antibody forms that may be effective clinical treatments for drug abuse, as well as several current and emerging production systems that could bridge the gap from discovery to patient use.
The concept of emergence appears in various places within the literature on expertise and expert practice. Here, I examine some of these applications of emergence in the light of two prominent accounts of emergence from the philosophy of science and philosophy of mind. I evaluate these accounts with respect to several specific contexts in which…
Full Text Available Natural entities—plants and animals, on the one hand, society, language, and culture, on the other—emerge through an assiduous diachronic effort, respond to diachronically developed needs, exist and function diachronically. However, through the instruments at his disposal, man can only perceive and grasp the “fragment”, seizing it for a prolonged instant, which explains his objective tendency to segment the spatiotemporal reality according to his own proportions and abilities. Reality itself, however, cannot be subjected to the unnatural segregation of one of its own products and elements, and cannot be fully comprehended in any other way than how it exists: as a whole. At the end of the synchronic road, what offers comprehension and understanding of the ontologically-becoming whole is the path of the diachronic method.
... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...
... Cocaine Heroin Inhalants Marijuana Prescription drugs, including opioids Drug abuse also plays a role in many major social problems, such as drugged driving, violence, stress, and child abuse. Drug abuse can lead to ...
Full Text Available ... Use and Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...
Full Text Available ... Drug Use and Kids Drug Use and Unborn Children Drug Use and Your Health Other Effects on ... Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids ...
... uses. Other uses of these drugs are abuse. Club drugs are also sometimes used as "date rape" drugs, to make someone unable to say no to or fight back against sexual assault. Abusing these drugs can ...