Marcio C. Mancini
Full Text Available Pharmacological treatment of obesity is an area of sudden changes,development of new drugs and treatment propositions. This articlepresents information on physiological agents that are currentlybeing used as well as drugs that were widely used but are nomore available.
Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS of a putative autoimmune origin characterized by neurologic dysfunction disseminated in space and time due to demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of the disease resulted in the introduction of numerous effective immunomodulatoty drugs having diverse mechanisms of action, modes of administration and risk-benefit profiles. This results in more complex albeit more promising treatment selection and choices. The epidemiology, clinical features, pathogenesis and diagnosis of the disease are discussed. The mode of action and main characteristics of current immunomodulatory drugs for MS and their place in the therapeutic algorithm of the disease based on evidence from clinical trials are described. Speculation on new paradigms, treatment goals and outcome measures aimed at improving the landscape of MS treatment is presented. Multiple disease, drug and patient-related factors should be taken into consideration when selecting the appropriate drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS.
Ujeyl, Mariam; Schlegel, Claudia; Gundert-Remy, Ursula
Until AMNOG came into effect Germany had free pricing of new drugs. Our exemplary work investigates the costs of new drugs that were licensed in the two years prior to AMNOG, and compares them to the costs of standard treatment that has been used in pivotal trials. Also, the important components of pharmaceutical prices will be illustrated. We retrospectively analysed the European Public Assessment Reports of proprietary medicinal products that the European Medicinal Agency initially approved in 2009 and 2010 and that were tested against an active control in at least one pivotal trial. If the standard treatment was a generic, the average pharmacy retail price of new drugs was 7.4 times (median 7.1) higher than that of standard treatment. If the standard treatment was an originator drug the average price was 1.4 times (median 1.2) higher than that of the new drug. There was no clear correlation of an increase in costs for new drugs and their "grade of innovation" as rated according to the criteria of Fricke. Our study shows that prices of new drugs must be linked to the evidence of comparative benefit; since German drug pricing is complex, cost saving effects obtained thereby will depend on a range of other rules and decisions. Copyright © 2013. Published by Elsevier GmbH.
McCarthy, Matthew W; Walsh, Thomas J
The widespread implementation of immunosuppressants, immunomodulators, hematopoietic stem cell transplantation and solid organ transplantation in clinical practice has led to an expanding population of patients who are at risk for invasive candidiasis, which is the most common form of fungal disease among hospitalized patients in the developed world. The emergence of drug-resistant Candida spp. has added to the morbidity associated with invasive candidiasis and novel therapeutic strategies are urgently needed. Areas covered: In this paper, we explore investigational agents for the treatment of invasive candidiasis, with particular attention paid to compounds that have recently entered phase I or phase II clinical trials. Expert opinion: The antifungal drug development pipeline has been severely limited due to regulatory hurdles and a systemic lack of investment in novel compounds. However, several promising drug development strategies have recently emerged, including chemical screens involving Pathogen Box compounds, combination antifungal therapy, and repurposing of existing agents that were initially developed to treat other conditions, all of which have the potential to redefine the treatment of invasive candidiasis.
Full Text Available Substance-use disorders (SUD cause severe problems both globally and locally. Research suggests that multiple addictions create a more complex illness. This study investigated whether in-patients admitted for SUD at three drug treatment centres in Durban, South Africa had other, undiagnosed addictions. It utilised a three-phase concurrent mixed-methods design and initially screened for gambling and sex addiction. Results showed that, of the sample of 123 participants, 54% had either sex or gambling and 24% had both addictions which current treatment programmes neither assessed for nor treated. Recommendations include suggestions to update current assessment and treatment approaches and the need to train professional staff at drug treatment centres.
Reas, Deborah L.; Grilo, Carlos M.
Introduction This study evaluated controlled treatment studies of pharmacotherapy for binge eating disorder (BED). Areas Covered The primary focus of the review was on phase II and III controlled trials testing medications for BED. A total of 46 studies were considered and 26 were reviewed in detail. BED outcomes included binge-eating remission, binge-eating frequency, associated eating-disorder psychopathology, associated depression, and weight loss. Expert Opinion Data from controlled trials suggests that certain medications are superior to placebo for stopping binge-eating and for producing faster reductions in binge eating, and - to varying degrees - for reducing associated eating-disorder psychopathology, depression, and weight loss over the short-term. Almost no data exist regarding longer-term effects of medication for BED. Except for topiramate, which reduces both binge eating and weight, weight loss is minimal with medications tested for BED. Psychological interventions and the combination of medication with psychological interventions produce binge-eating outcomes that are superior to medication-only approaches. Combining medications with psychological interventions does not significantly enhance binge-eating outcomes, although the addition of certain medications enhances weight losses achieved with cognitive-behavioral therapy and behavioral weight loss, albeit modestly. PMID:24460483
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.
Full Text Available Theodor H Lippert,1 Hans-Jörg Ruoff,1 Manfred Volm2 1Medical Faculty, University of Tübingen, Tübingen, Germany; 2Medical Faculty, University of Heidelberg, Heidelberg, Germany Abstract: Clinical practice guidelines are indispensable for such a variable disease as malignant solid tumors, with the complex possibilities of drug treatment. The current guidelines may be criticized on several points, however. First, there is a lack of information on the outcome of treatment, such as the expected success and failure rates. Treating not only drug responders but also nonresponders, that is, patients with drug resistance, must result in failures. There is no mention of the possibility of excluding the drug nonresponders, identifiable by special laboratory tests and no consideration is given to the different side effects of the recommended drug regimens. Nor are there any instructions concerning tumor cases for which anticancer drug treatment is futile. In such cases, early palliative care may lead to significant improvements in both life quality and life expectancy. Not least, there is no transparency concerning the preparation of the guidelines: persons cannot be identified who could give a statement of conflicts of interest, and responsibility is assumed only by anonymous medical associations. A revision of the current guidelines could considerably improve cancer treatment. Keywords: anticancer drugs, quality of guidelines, critical remarks
Lippert, Theodor H; Ruoff, Hans-Jörg; Volm, Manfred
Clinical practice guidelines are indispensable for such a variable disease as malignant solid tumors, with the complex possibilities of drug treatment. The current guidelines may be criticized on several points, however. First, there is a lack of information on the outcome of treatment, such as the expected success and failure rates. Treating not only drug responders but also nonresponders, that is, patients with drug resistance, must result in failures. There is no mention of the possibility of excluding the drug nonresponders, identifiable by special laboratory tests and no consideration is given to the different side effects of the recommended drug regimens. Nor are there any instructions concerning tumor cases for which anticancer drug treatment is futile. In such cases, early palliative care may lead to significant improvements in both life quality and life expectancy. Not least, there is no transparency concerning the preparation of the guidelines: persons cannot be identified who could give a statement of conflicts of interest, and responsibility is assumed only by anonymous medical associations. A revision of the current guidelines could considerably improve cancer treatment.
Möbius, E; Leopold, H C; Paulus, W M
Carbamazepine continues to be the most useful drug in the treatment of trigeminal neuralgia. Diphenylhydantoin may be given in addition to or instead of Carbamazepine. Refractory cases may benefit from combination with Baclofen or Chlorphenesin. In cases of persistent pain the concomitant use of tricyclic antidepressant drugs is recommended. If pain continues in spite of multiple medical therapies or if serious side effects develop, then surgical procedures such as percutaneous controlled thermocoagulation or microvascular decompression are indicated. Percutaneous thermocoagulation is associated with the lowest mortality and morbidity rate and can easily be repeated. Microvascular decompression should especially be offered to young patients, who want to avoid any sensory disturbance of the face, and recommended for other patients for whom all other forms of therapy including percutaneous thermocoagulation have failed.
Kettenbach, Joachim; Stadler, Alfred; Katzler, Isabella v.; Schernthaner, Ruediger; Blum, Melanie; Lammer, Johannes; Rand, Thomas
Transarterial chemoembolization (TACE) involves the emulsification of a chemotherapeutic agent in a viscous drug carrier, delivered intra-arterially to liver tumor for maximum effect. TACE reduces arterial inflow, diminishes washout of the chemotherapeutic agent, and decreases systemic exposure. Despite evidence of some clinical success with TACE, a new type of microspheres with drug-eluting capabilities may offer a precisely controlled and sustainable release of the chemotherapeutic agent into the tumor bed. In animal trials tumor necrosis (approaching 100%) was greatest at 7 days, with significantly lower plasma concentrations of doxorubicin than in control animals treated with doxorubicin intra-arterially. Clinically, drug-eluting microspheres loaded with doxorubicin, either at 75 mg/m 2 or at a fixed dose of 150 mg, were used recently and no severe disorders of the hepatic function were observed postprocedure, while a substantial reduction of the fetoprotein levels occurred. An interim analysis of the first 15 patients from the Hong Kong group at 3 months showed an objective response rate of 61.54% and 53.84% according to EASL criteria and RECIST criteria, respectively, and a survival rate of 93.3%. In this paper we present how to use microspheres loaded with doxorubicin and review their clinical value and preliminary performance for treatment of unresectable liver cancer
Udedibia, Emeka; Kaminetsky, Jed
Hypogonadism is the most common endocrine disorder, which affects men of all age groups. Recent shifts in public awareness, increased screening and recognition of symptoms and updated diagnostic criteria have led to an increase in men diagnosed as hypogonadal, including middle-aged and older men who previously would have been considered eugonadal. The increase in testosterone replacement therapy (TRT) has paralleled an increase in advancements of treatment options. Although current therapies are highly efficacious for many men, there remains a need for newer therapies that are more cost-effective, preserve ease of use and administration, mitigate undesirable effects and closely mimic physiological levels of testosterone. In this review, the authors discuss current TRTs and therapies in development for the treatment of hypogonadism. The focus is on therapies under Phase II investigation or those who have recently completed Phase II study. With several new therapies in development, the authors expect advancements in achieving treatment benchmarks that meet the needs of the individual symptomatic hypogonadal male. Increased public awareness of hypogonadism and TRT has led to a welcomed expansion in the choice of TRT options. These include new delivery systems, formulations, routes of administration and non-testosterone modalities.
U.S. Department of Health & Human Services — The Drug Establishments Current Registration Site (DECRS) is a database of current information submitted by drug firms to register establishments (facilities) which...
Baker, A; Kochan, N; Dixon, J; Wodak, A; Heather, N
This study compares the injecting and sexual risk-taking behaviour among injecting drug users (IDUs) currently, previously and never enrolled in methadone maintenance treatment (MMT). All subjects had injected during the 6 months prior to the day of interview. The current MMT group showed significantly lower injecting risk-taking behaviour subscale scores on the HIV Risk-taking Behaviour Scale (HRBS) of the Opiate Treatment Index than the previous MMT and non-MMT groups together. The current MMT group differed from the other two groups in the frequency of injecting and cleaning of injection equipment with bleach. There was no difference between the current MMT group and the other two groups combined in sexual risk-taking behaviour scores on the HRBS. There were no differences between the previous MMT and non-MMT groups in injecting and sexual risk-taking behaviour. HIV seroprevalence was low and there was no difference in seroprevalence between groups. Thus, IDUs currently enrolled in MMT are at reduced risk for HIV infection when compared with IDUs who have previously or never been enrolled in MMT. However, the absence of a difference between the current MMT and other two groups in frequency of sharing behaviours suggests the need for additional strategies among MMT clients to reduce needle-sharing. Possible strategies include the application of relapse prevention interventions and the availability of sterile injecting equipment in MMT clinics. Further research is needed to identify factors which increase attraction and retention of IDUs to MMT.
Migraine is a common disorder with a female prevalence of 17% and a male prevalence of 9%. Migraine is most often disabling and the patients need treatment of the attacks. The introduction of triptans has been a revolution for many migraine patients but only a minority of patients use these speci...
Pau, Alice K; George, Jomy M
The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date. Published by Elsevier Inc.
Full Text Available The pharmacological treatment of mesial temporal lobe epilepsy (mTLE, the most common epileptic syndrome in adults, is still unsatisfactory, as one third of the patients are or become refractory to antiepileptic agents. Refractoriness may depend upon drug-induced alterations, but the disease per se may also undergo a progressive evolution that affects the sensitivity to drugs. mTLE has been shown to be associated with a dysfunction of the inhibitory signaling mediated by GABAA receptors. In particular, the repetitive activation of GABAA receptors produces a use-dependent decrease (rundown of the evoked currents (IGABA, which is markedly enhanced in the hippocampus and cortex of drug-resistant mTLE patients. This phenomenon has been also observed in the pilocarpine model, where the increased IGABA rundown is observed in the hippocampus at the time of the first spontaneous seizure, then extends to the cortex and remains constant in the chronic phase of the disease. Here, we examined the sensitivity of IGABA to pharmacological modulation. We focused on the antiepileptic agent levetiracetam and on the neurotrophin BDNF, which were previously reported to attenuate mTLE-induced increased rundown in the chronic human tissue. In the pilocarpine model, BDNF displayed a paramount effect, decreasing rundown in the hippocampus at the time of the first seizure, as well as in the hippocampus and cortex in the chronic period. In contrast, levetiracetam did not affect rundown in the hippocampus, but attenuated it in the cortex. Interestingly, this effect of levetiracetam was also observed on the still unaltered rundown observed in the cortex at the time of the first spontaneous seizure. These data suggest that the sensitivity of GABAA receptors to pharmacological interventions undergoes changes during the natural history of mTLE, implicating that the site of seizure initiation and the timing of treatment may highly affect the therapeutic outcome.
Kumar, Rajiv; Singh, Jagjit
Biologic products are being developed over the past three decades. The expiry of patent protection for many biological medicines has led to the development of biosimilars in UK or follow on biologics in USA. This article reviews the literature on biosimilar drugs that covers the therapeutic status and regulatory guidelines. Appraisal of published articles from peer reviewed journals for English language publications, search from PubMed, and guidelines from European Medicines Agency, US Food Drug Administration (FDA) and India were used to identify data for review. Literature suggest that biosimilars are similar biological products, i.e., comparable but not identical to the reference product, are not generic version of innovator product and do not ensure therapeutic equivalence. Biosimilars present more challenges than conventional generics and marketing approval is also more complicated. To improve access, US Congress passed the Biologics Price Competition and Innovation act 2009 and US FDA allowed "abbreviated pathway" for their approval. U.S law has defined new standards and terms and EMA scientific guidelines have also set detailed approval standards. India being one of the most preferred manufacturing destinations of biosimilars, there is a need for stringent safety and regulatory guidelines. The New India Guidelines "Draft Guidelines on Similar Biologics were announced in June 2012, by Department of Biotechnology at Boston bio and available online.
Ponzano, Stefano; Nigrelli, Giulia; Fregonese, Laura; Eichler, Irmgard; Bertozzi, Fabio; Bandiera, Tiziano; Galietta, Luis J V; Papaluca, Marisa
In this article we analyse the current authorised treatments and trends in early drug development for cystic fibrosis (CF) in the European Union for the time period 2000-2016. The analysis indicates a significant improvement in the innovation and development of new potential medicines for CF, shifting from products that act on the symptoms of the disease towards new therapies targeting the cause of CF. However, within these new innovative medicines, results for CF transmembrane conductance regulator (CFTR) modulators indicate that one major challenge for turning a CF concept product into an actual medicine for the benefit of patients resides in the fact that, although pre-clinical models have shown good predictability for certain mutations, a good correlation to clinical end-points or biomarkers ( e.g. forced expiratory volume in 1 s and sweat chloride) for all mutations has not yet been achieved. In this respect, the use of alternative end-points and innovative nonclinical models could be helpful for the understanding of those translational discrepancies. Collaborative endeavours to promote further research and development in these areas as well as early dialogue with the regulatory bodies available at the European competent authorities are recommended. Copyright ©ERS 2018.
... this page: //medlineplus.gov/ency/patientinstructions/000314.htm Cholesterol - drug treatment To use the sharing features on ... treatment; Hardening of the arteries - statin Statins for Cholesterol Statins reduce your risk of heart disease, stroke, ...
San-Juan, Daniel; Sarmiento, Carlos Ignacio; González, Katia Márquez; Orenday Barraza, José Manuel
Transcranial direct current stimulation (tDCS) is a reemerged noninvasive cerebral therapy used to treat patients with epilepsy, including focal cortical dysplasia, with controversial results. We present a case of a 28-year-old female with left frontal cortical dysplasia refractory to antiepileptic drugs, characterized by 10-15 daily right tonic hemi-body seizures. The patient received a total of seven sessions of cathodal tDCS (2 mA, 30 min). The first three sessions were applied over three consecutive days, and the remaining four sessions of tDCS were given each at 2-week intervals. At the 1-year follow-up, the patient reported to have a single seizure per month and only mild adverse events.
De Lossada, A; Oteo-Álvaro, Á; Giménez, S; Oyagüez, I; Rejas, J
To assess the cost-effectiveness of celecoxib and non-selective non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis in clinical practice in Spain. A decision-tree model using distribution, doses, treatment duration and incidence of GI and CV events observed in the pragmatic PROBE-designed «GI-Reasons» trial was used for cost-effectiveness. Effectiveness was expressed in terms of event averted and quality-adjusted life-years (QALY) gained. QALY were calculated based on utility decrement in case of any adverse events reported in GI-Reasons trial. The National Health System perspective in Spain was applied; cost calculations included current prices of drugs plus cost of adverse events occurred. The analysis was expressed as an incremental cost-effectiveness ratio per QALY gained and per event averted. One-way and probabilistic analyses were performed. Compared with non-selective non-steroidal anti-inflammatory drugs, at current prices, celecoxib treatment had higher overall treatment costs €201 and €157, respectively. However, celecoxib was associated with a slight increase in QALY gain and significantly lower incidence of gastrointestinal events (pcost-effectiveness ratio of €13,286 per QALY gained and €4,471 per event averted. Sensitivity analyses were robust, and confirmed the results of the base case. Celecoxib at current price may be considered as a cost-effective alternative vs. non-selective non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis in daily practice in the Spanish NHS. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.
Morgan, Gilberto; Aftimos, Philippe; Awada, Ahmad
Precision oncology has been a strategy of prevention, screening, and treatment. Although much has been invested, have the results fallen so far short of the promise? The advancement of technology and research has opened new doors, yet a variety of pitfalls are present. This review presents the successes, failures, and opportunities of precision oncology in the current landscape. The use of targeted gene sequencing and the overwhelming results of superresponders have generated much excitement and support for precision oncology from the medical community. Despite notable successes, many challenges still pave the way of precision oncology: intratumoral heterogeneity, the need for serial biopsies, availability of treatments, target prioritization, ethical issues with germline incidental findings, medical education, clinical trial design, and costs. Precision oncology shows much potential through the use of next-generation sequencing and molecular advances, but does this potential warrant the investment? There are many obstacles on the way of this technology that should make us question if the investment (both monetary and man-hours) will live up to the promise. The review aims to not criticize this technology, but to give a realistic view of where we are, especially regarding cancer treatment and prevention.
that professionals activate to make sense of inauthenticity: (1) professionals routinely refer to what this study labels the story of institutional conformism, portraying institutionalized clients who have developed a habit of saying the “right” things rather than the “real” things, (2) in the somewhat taboo story...... of ulterior motives, clients are interpreted as making inauthentic claims because they want to obtain something externally from drug treatment (e.g., avoid prison or work training programs), and (3) the story of disorders explains inauthenticity as a result of pathology. The study illuminates how...
Miovský, Michal; Gajdošíková, H.
Roč. 16, č. 4 (2005), s. 262-266 ISSN 0955-3959 Institutional research plan: CEZ:AV0Z70250504 Keywords : Criminal offences * drug crime * illicit drugs * drug user * prevetntion and treatment measures Subject RIV: AN - Psychology
Guaita, Marc; Högl, Birgit
Despite numerous case reports, the evidence for treatment of bruxism is still low. Different treatment modalities (behavioral techniques, intraoral devices, medications, and contingent electrical stimulation) have been applied. A clinical evaluation is needed to differentiate between awake bruxism and sleep bruxism and rule out any medical disorder or medication that could be behind its appearance (secondary bruxism). A polysomnography is required only in a few cases of sleep bruxism, mostly when sleep comorbidities are present. Counselling with regard to sleep hygiene, sleep habit modification, and relaxation techniques has been suggested as the first step in the therapeutic intervention, and is generally considered not harmful, despite low evidence of any efficacy. Occlusal splints are successful in the prevention of dental damage and grinding sounds associated with sleep bruxism, but their effects on reducing bruxism electromyographic (EMG) events are transient. In patients with psychiatric and sleep comorbidities, the acute use of clonazepam at night has been reported to improve sleep bruxism, but in the absence of double-blind randomized trials, its use in general clinical practice cannot be recommended. Severe secondary bruxism interfering with speaking, chewing, or swallowing has been reported in patients with neurological disorders such as in cranial dystonia; in these patients, injections of botulinum toxin in the masticatory muscles may decrease bruxism for up to 1-5 months and improve pain and mandibular functions. Long-term studies in larger and better specified samples of patients with bruxism, comparing the effects of different therapeutic modalities on bruxism EMG activity, progression of dental wear, and orofacial pain are current gaps of knowledge and preclude the development of severity-based treatment guidelines.
The main goal of the theoretical part of submitted theses is to describe the field of specialized treatment of imprisoned drug users. The author's emphasis is to put the specialized treatment to a broader frame of the Risk-needs theory as well as to the frame of physical diseases and mental disorders that are often associated with addiction or drug abuse. Different kinds of specialized interventions that are usually used for treatment of imprisoned drug users in different countries are descri...
Li, Huiling; Chintalapudi, Sumana R; Jablonski, Monica M
Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly. Atrophic AMD, including early, intermediate and geographic atrophy (GA), accounts for ~90% of all cases. It is a multifactorial degeneration characterized by chronic inflammation, oxidative stress and aging components. Although no FDA-approved treatment yet exists for the late stage of atrophic AMD, multiple pathological mechanisms are partially known and several promising therapies are in various stages of development. Areas covered: Underlying mechanisms that define atrophic AMD will help provide novel therapeutic targets that will address this largely unmet clinical need. The purpose of this paper is to review current promising drugs that are being evaluated in clinical trials. Because no pharmacological treatments are currently available for late stage of atrophic AMD, any new therapy would have extensive market potential. Expert opinion: The number of AMD patients is predicted to increase to ~30 million worldwide by 2020. In response to this enormous unmet clinical need, new promising therapies are being developed and evaluated in clinical trials. We propose that the assessment of novel interventions will also need to consider the genotypes of participants, as the benefit may be determined by polymorphisms in an individual's genetic background.
Guaita, Marc; H?gl, Birgit
Opinion statement Despite numerous case reports, the evidence for treatment of bruxism is still low. Different treatment modalities (behavioral techniques, intraoral devices, medications, and contingent electrical stimulation) have been applied. A clinical evaluation is needed to differentiate between awake bruxism and sleep bruxism and rule out any medical disorder or medication that could be behind its appearance (secondary bruxism). A polysomnography is required only in a few cases of slee...
Retinoblastoma is a highly malignant intraocular tumor of childhood which requires prompt treatment once the diagnosis has been established. The traditionally accepted methods include enucleation, external irradiation, scleral plaque irradiation, photocoagulation, cryotherapy, chemotherapy. This article will provide an update on the modern methods of treatment which are available for retinoblastoma. It is based largely on personal experience with approximately 200 new patients with retinoblastoma who were evaluated and treated between 1974 and 1984 in the Oncology Service of Wills Eye Hospital with an overall survival of 97%. This article will be an overall review which will not go into statistical detail. (Auth.)
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...
Harada, T.; Shimaoka, K.; Mimura, T.; Ito, K.
In this review we have described the rationale for the appropriate treatment of patients with Graves' disease. Because the etiology of this disorder remains obscure, its management remains controversial. Since antithyroid drugs and radioiodine became readily available in the early 1950s, they have been widely used for the treatment of thyrotoxicosis, and the number of cases treated surgically has markedly decreased. However, almost four decades of experience have disclosed an unexpectedly high incidence of delayed hypothyroidism after radioiodine treatment and a low remission rate after antithyroid therapy. As a result, surgery is again being advocated as the treatment of choice. The three modalities of treatment have different advantages and disadvantages, and selection of treatment is of importance. In principle, we believe that for most patients a subtotal thyroidectomy should be performed after the patient has been rendered euthyroid by antithyroid drugs. We attempt to leave a thyroid remnant of 6 to 8 gm.36 references
Zugazagoitia, Jon; Guedes, Cristiano; Ponce, Santiago; Ferrer, Irene; Molina-Pinelo, Sonia; Paz-Ares, Luis
In this review, we highlight the current concepts and discuss some of the current challenges and future prospects in cancer therapy. We frequently use the example of lung cancer. We conducted a nonsystematic PubMed search, selecting the most comprehensive and relevant research articles, clinical trials, translational papers, and review articles on precision oncology and immuno-oncology. Papers were prioritized and selected based on their originality and potential clinical applicability. Two major revolutions have changed cancer treatment paradigms in the past few years: targeting actionable alterations in oncogene-driven cancers and immuno-oncology. Important challenges are still ongoing in both fields of cancer therapy. On the one hand, druggable genomic alterations are diverse and represent only small subsets of patients in certain tumor types, which limits testing their clinical impact in biomarker-driven clinical trials. Next-generation sequencing technologies are increasingly being implemented for molecular prescreening in clinical research, but issues regarding clinical interpretation of large genomic data make their wide clinical use difficult. Further, dealing with tumor heterogeneity and acquired resistance is probably the main limitation for the success of precision oncology. On the other hand, long-term survival benefits with immune checkpoint inhibitors (anti-programmed death cell protein-1/programmed death cell ligand-1[PD-1/L1] and anti-cytotoxic T lymphocyte antigen-4 monoclonal antibodies) are restricted to a minority of patients, and no predictive markers are yet robustly validated that could help us recognize these subsets and optimize treatment delivery and selection. To achieve long-term survival benefits, drug combinations targeting several molecular alterations or cancer hallmarks might be needed. This will probably be one of the most challenging but promising precision cancer treatment strategies in the future. Targeting single molecular
Turanli, Beste; Grøtli, Morten; Boren, Jan; Nielsen, Jens; Uhlen, Mathias; Arga, Kazim Y; Mardinoglu, Adil
Drug repositioning has gained attention from both academia and pharmaceutical companies as an auxiliary process to conventional drug discovery. Chemotherapeutic agents have notorious adverse effects that drastically reduce the life quality of cancer patients so drug repositioning is a promising strategy to identify non-cancer drugs which have anti-cancer activity as well as tolerable adverse effects for human health. There are various strategies for discovery and validation of repurposed drugs. In this review, 25 repurposed drug candidates are presented as result of different strategies, 15 of which are already under clinical investigation for treatment of prostate cancer (PCa). To date, zoledronic acid is the only repurposed, clinically used, and approved non-cancer drug for PCa. Anti-cancer activities of existing drugs presented in this review cover diverse and also known mechanisms such as inhibition of mTOR and VEGFR2 signaling, inhibition of PI3K/Akt signaling, COX and selective COX-2 inhibition, NF-κB inhibition, Wnt/β-Catenin pathway inhibition, DNMT1 inhibition, and GSK-3β inhibition. In addition to monotherapy option, combination therapy with current anti-cancer drugs may also increase drug efficacy and reduce adverse effects. Thus, drug repositioning may become a key approach for drug discovery in terms of time- and cost-efficiency comparing to conventional drug discovery and development process.
The use of 131 I in the treatment of thyroid diseases is described. The therapeutic possibilities of application for ther radionuklide, e.g. phosphorus 32, gold 198, or yttrium 90 are discussed. (VJ) [de
Wang, Hongzhi; Yin, Yuanyuan; Wang, Peiqi; Xiong, Chenyu; Huang, Lingyu; Li, Sijia; Li, Xinyi; Fu, Leilei
Cancer is a deadly disease with increasing incidence and mortality rates and affects the life quality of millions of people per year. The past 15 years have witnessed the rapid development of targeted therapy for cancer treatment, with numerous anticancer drugs, drug targets and related gene mutations been identified. The demand for better anticancer drugs and the advances in database technologies have propelled the development of databases related to anticancer drugs. These databases provide systematic collections of integrative information either directly on anticancer drugs or on a specific type of anticancer drugs with their own emphases on different aspects, such as drug-target interactions, the relationship between mutations in drug targets and drug resistance/sensitivity, drug-drug interactions, natural products with anticancer activity, anticancer peptides, synthetic lethality pairs and histone deacetylase inhibitors. We focus on a holistic view of the current situation and future usage of databases related to anticancer drugs and further discuss their strengths and weaknesses, in the hope of facilitating the discovery of new anticancer drugs with better clinical outcomes.
Yasinzai, Masoom; Khan, Momin; Nadhman, Akhtar; Shahnaz, Gul
Leishmaniasis is a complex of diseases with numerous clinical manifestations for instance harshness from skin lesions to severe disfigurement and chronic systemic infection in the liver and spleen. So far, the most classical leishmaniasis therapy, despite its documented toxicities, remains pentavalent antimonial compounds. The arvailable therapeutic modalities for leishmaniasis are overwhelmed with resistance to leishmaniasis therapy. Mechanisms of classical drug resistance are often related with the lower drug uptake, increased efflux, the faster drug metabolism, drug target modifications and over-expression of drug transporters. The high prevalence of leishmaniasis and the appearance of resistance to classical drugs reveal the demand to develop and explore novel, less toxic, low cost and more promising therapeutic modalities. The review describes the mechanisms of classical drug resistance and potential drug targets in Leishmania infection. Moreover, current drug-delivery systems and future perspectives towards Leishmaniasis treatment are also covered.
Alopecia is the term used to describe hairless areas of the scalp. They can follow a specific pattern, be diffuse or circumscript. Androgenetic alopecia (AGA) follows a pattern: in men thinning of temples and vertex up to total baldness; in women thinning of the midline or parietal area. Lack of iron or cytostatic drugs cause diffuse alopecia, while in autoimmune diseases such as alopecia areata or lichen planus bizarre shapes of hairless areas are observed. For therapy, the following medications are used: topical minoxidil solution for AGA of men and women; systemic finasteride 1 mg for men with AGA; topical diphencyprone immunotherapy for alopecia areata; systemic antimycotic agents for tinea capitis; antibiotics such as clindamycin and rifampicin for folliculitis decalvans; systemic corticosteroids and isotretinoin for folliculitis et perifolliculitis capitis abscedens et suffodiens; topical corticosteroids for lichen planus and Kossard's frontal fibrosing alopecia.
Cihlar, Tomas; Fordyce, Marshall
Current antiviral treatments can reduce HIV-associated morbidity, prolong survival, and prevent HIV transmission. Combination antiretroviral therapy (cART) containing preferably three active drugs from two or more classes is required for durable virologic suppression. Regimen selection is based on virologic efficacy, potential for adverse effects, pill burden and dosing frequency, drug-drug interaction potential, resistance test results, comorbid conditions, social status, and cost. With prolonged virologic suppression, improved clinical outcomes, and longer survival, patients will be exposed to antiretroviral agents for decades. Therefore, maximizing the safety and tolerability of cART is a high priority. Emergence of resistance and/or lack of tolerability in individual patients require availability of a range of treatment options. Development of new drugs is focused on improving safety (e.g. tenofovir alafenamide) and/or resistance profile (e.g. doravirine) within the existing drug classes, combination therapies with improved adherence (e.g. single-tablet regimens), novel mechanisms of action (e.g. attachment inhibitors, maturation inhibitors, broadly neutralizing antibodies), and treatment simplification with infrequent dosing (e.g. long-acting injectables). In parallel with cART innovations, research and development efforts focused on agents that target persistent HIV reservoirs may lead to prolonged drug-free remission and HIV cure. Copyright © 2016 Gilead Sciences, Inc. Published by Elsevier B.V. All rights reserved.
Silvio-Estaba, Leonardo; Madrazo-González, Zoilo; Ramos-Rubio, Emilio
The therapeutic and diagnostic approach of liver trauma injuries (by extension, of abdominal trauma) has evolved remarkably in the last decades. The current non-surgical treatment in the vast majority of liver injuries is supported by the accumulated experience and optimal results in the current series. It is considered that the non-surgical treatment of liver injuries has a current rate of success of 83-100%, with an associated morbidity of 5-42%. The haemodynamic stability of the patient will determine the applicability of the non-surgical treatment. Arteriography with angioembolisation constitutes a key technical tool in the context of liver trauma. Patients with haemodynamic instability will need an urgent operation and can benefit from abdominal packing techniques, damage control and post-operative arteriography. The present review attempts to contribute to the current, global and practical management in the care of liver trauma.
The metabolic syndrome is a constellation of risk factors for cardiovascular diseases including: abdominal obesity, a decreased ability to metabolize glucose (increased blood glucose levels and/or presence of insulin resistance), dyslipidemia, and hypertension. Patients who have developed this syndrome have been shown to be at an increased risk of developing cardiovascular disease and/or type 2 diabetes. Genetic factors and the environment both are important in the development of the metabolic syndrome, influencing all single components of this syndrome. The goals of therapy are to treat the underlying cause of the syndrome, to reduce morbidity, and to prevent complications, including premature death. Lifestyle modification is the preferred first-step treatment of the metabolic syndrome. There is no single effective drug treatment affecting all components of the syndrome equally known yet. However, each component of metabolic syndrome has independent goals to be achieved, so miscellaneous types of drugs are used in the treatment of this syndrome, including weight losing drugs, antidiabetics, antihypertensives, antilipemic and anticlothing drugs etc. This article provides a brief insight into contemporary drug treatment of components the metabolic syndrome.
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
Toggweiler, Stefan; Jamshidi, Peiman; Cuculi, Florim
Current therapy for stable angina includes surgical and percutaneous revascularization, which has been improved tremendously over the last decades. Smoking cessation and regular exercise are the cornerstone for prevention of further cerebrovascular events. Medical treatment includes treatment of cardiovascular risk factors and antithrombotic management, which can be a challenge in some patients. Owing to the fact the coronary revascularization is readily accessible these days in many industrialized countries, the importance of antianginal therapy has decreased over the past years. This article presents a contemporary overview of the management of patients with stable angina in the year 2015.
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
Simonini, Gabriele; Druce, Katie; Cimaz, Rolando; Macfarlane, Gary J; Jones, Gareth T
To summarize evidence regarding the effectiveness of anti-tumor necrosis factor α (anti-TNFα) treatments in childhood autoimmune chronic uveitis (ACU), refractory to previous disease-modifying antirheumatic drugs (DMARDs). A systematic search between January 2000 and October 2012 was conducted using EMBase, Ovid Medline, Evidence-Based Medicine (EBM) Reviews: American College of Physicians Journal Club, Cochrane libraries, and EBM Reviews. Studies investigating the efficacy of anti-TNFα therapy, in children ages ≤16 years, as the first treatment with a biologic agent for ACU, refractory to topical and/or systemic steroid therapy and at least 1 DMARD, were eligible for inclusion. The primary outcome measure was the improvement of intraocular inflammation, as defined by the Standardization of Uveitis Nomenclature Working Group criteria. We determined a combined estimate of the proportion of children responding to anti-TNFα treatment, including etanercept (ETA), infliximab (INF), or adalimumab (ADA). We initially identified 989 articles, of which 148 were potentially eligible. In total, 22 retrospective chart reviews and 1 randomized clinical trial were deemed eligible, thus including 229 children (ADA: n = 31, ETA: n = 54, and INF: n = 144). On pooled analysis of observational studies, the proportion of responding children was 87% (95% confidence interval [95% CI] 75-98%) for ADA, 72% (95% CI 64-79%) for INF, and 33% (95% CI 19-47%) for ETA. There was no difference in the proportion of responders between ADA and INF (χ(2) = 3.06, P = 0.08), although both showed superior efficacy compared with ETA (ADA versus ETA: χ(2) = 20.9, P < 0.001 and INF versus ETA: χ(2) = 20.9, P < 0.001). Although randomized controlled trials are needed, the available evidence suggests that INF and ADA provide proven similar benefits in the treatment of childhood ACU, and they are both superior to ETA. Copyright © 2014 by the American College of Rheumatology.
PURPOSE: The incidence of osteoporosis-related fractures will increase substantially over the coming decades as the population ages globally. This has important economic and public health implications, contributing substantially to morbidity and excess mortality in this population. METHODS: When prescribing for older patients the effectiveness profile of drugs needs to be balanced against their tolerability in individual patients. RESULTS: Currently we have good anti-fracture data to support the use of many available anti-resorptive and anabolic drugs including bisphosphonates, strontium ranelate and recombinant human parathyroid hormone. We also have evidence to demonstrate the importance of calcium and vitamin D repletion in these patients. However, in recent years our understanding of normal bone physiology and the mechanisms underlying the development of osteoporosis has significantly advanced and this has led to the development of new therapies. Novel agents, particularly denosumab, but also inhibitors of cathepsin K and anabolic agents that act on Wnt signalling, will increase the therapeutic options for clinicians in the coming years. CONCLUSION: This review discusses the evidence supporting the use of currently available treatment options for osteoporosis and potential future advances in drug therapy. Particular consideration should be given when prescribing for certain older patients who have issues with compliance or tolerance and also in those with co-morbidities or levels of frailty that may restrict the choice of therapy. Understanding the evidence for the benefit and possible harm of osteoporosis treatments is critical to appropriate management of this patient population.
Diabetes is a serious chronic condition,which increase the risk of cardiovascular diseases,kidney failure and nerve damage leading to amputation.Furthermore the ocular complications include diabetic macular edema,is the leading cause of blindness among adults in the industrialized countries.Today,blindness from diabetic macular edema is largely preventable with timely detection and appropriate interventional therapy.The treatment should include an optimized control of glycemia,arterial tension,lipids and renal status.The photocoagulation laser is currently restricted to focal macular edema in some countries,but due the high cost of intravitreal drugs,the use of laser treatment for focal and diffuse diabetic macular edema(DME),can be valid as gold standard in many countries.The intravitreal anti vascular endothelial growth factor drugs(ranibizumab and bevacizumab),are indicated in the treatment of all types of DME,but the correct protocol for administration should be defined for the different Retina Scientific Societies.The corticosteroids for diffuse DME,has a place in pseudophakic patients,but its complications restricted the use of these drugs for some patients.Finally the intravitreal interface plays an important role and its exploration is mandatory in all DME patients.
Fries, J F
Rheumatoid arthritis (RA) has traditionally been treated using the pyramid approach, in which non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment and disease-modifying anti-rheumatic drugs (DMARDs) are introduced relatively late in the disease. This approach is no longer valid. Previously regarded as a benign disease, RA is now recognized as causing substantial morbidity and mortality, as do the NSAIDs used in treatment. DMARDs are more effective in controlling the pain and disability of RA than NSAIDs, and are often no more toxic. The current treatment paradigm emphasizes early, consistent use of DMARDs. A 'sawtooth' strategy of DMARD use has been proposed, in which a rising but low level of disability triggers a change in therapy. Determining the most clinically useful DMARD combinations and the optimal sequence of DMARD use requires effectiveness studies, Bayesian approaches and analyses of long-term outcomes. Such approaches will allow optimization of multiple drug therapies in RA, and should substantially improve the long-term outcome for many patients.
Giuliari, Gian Paolo; Simpson, E. Rand (Princess Margaret Hospital, Univ. of Toronto, Dept. of Ophthalmology and Vision Sciences, Toronto (Canada)), e-mail: firstname.lastname@example.org; Sadaka, Ama (Schepens Eye Research Inst., Boston, MA (United States)); Hinkle, David M. (Massachusetts Eye Research and Surgery Institution, Cambridge, MA (United States))
Background. To review the currently available therapeutic modalities for radiation retinopathy (RR), including newer investigational interventions directed towards specific aspects of the pathophysiology of this refractory complication. Methods. A review of the literature encompassing the pathogenesis of RR and the current therapeutic modalities available was performed. Results. RR is a chronic and progressive condition that results from exposure to any source of radiation. It might be secondary to radiation treatment of intraocular tumors such as choroidal melanomas, retinoblastomas, and choroidal metastasis, or from unavoidable exposure to excessive radiation from the treatment of extraocular tumors like cephalic, nasopharyngeal, orbital, and paranasal malignancies. After the results of the Collaborative Ocular Melanoma Study, most of the choroidal melanomas are being treated with plaque brachytherapy increasing by that the incidence of this radiation complication. RR has been reported to occur in as many as 60% of eyes treated with plaque radiation, with higher rates associated with larger tumors. Initially, the condition manifests as a radiation vasculopathy clinically seen as microaneurysms and telangiectasis, with posterior development of retinal hard exudates and hemorrhages, macular edema, neovascularization and tractional retinal detachment. Regrettably, the management of these eyes remains limited. Photodynamic therapy, laser photocoagulation, oral pentoxyphylline and hyperbaric oxygen have been attempted as treatment modalities with inconclusive results. Intravitreal injections of anti-vascular endothelial growth factor such as bevacizumab, ranibizumab and pegaptanib sodium have been recently used, also with variable results. Discussion. RR is a common vision threatening complication following radiation therapy. The available therapeutic options are limited and show unsatisfactory results. Further large investigative studies are required for developing
Osborn, Gerald G; Saunders, Amanda Vaughn
There is neither proven effective prevention for Alzheimer disease nor a cure for patients with this disorder. Nevertheless, a spectrum of biopsychosocial therapeutic measures is available for slowing progression of the illness and enhancing quality of life for patients. These measures include a range of educational, psychological, social, and behavioral interventions that remain fundamental to effective care. Also available are a number of pharmacologic treatments, including prescription medications approved by the US Food and Drug Administration for Alzheimer disease, "off-label" uses of medications to manage target symptoms, and controversial complementary therapies. Physicians must make the earliest possible diagnosis to use these treatments most effectively. Physicians' goals should be to educate patients and their caregivers, to plan long-term care options, to maximally manage concurrent illnesses, to slow and ameliorate the most disabling symptoms, and to preserve effective functioning for as long as possible. The authors review the various current treatments for patients with Alzheimer disease.
Apra, Caroline; Peyre, Matthieu; Kalamarides, Michel
With an annual incidence of 5/100,000, meningioma is the most frequent primary tumor of the central nervous system. Risk factors are radiotherapy and hormone intake. Most meningiomas are grade I benign tumors, but up to 15% are atypical and 2% anaplastic according to the WHO 2016 histological criteria. Areas covered: This review details the current standard therapy based on international guidelines and recent literature, and describes new approaches developed to treat refractory cases. First-line treatments are observation and surgery, but adjuvant radiotherapy/radiosurgery is discussed for atypical and indicated for anaplastic meningiomas. The most problematic cases include skull base meningiomas that enclose vasculo-nervous structures and surgery- and radiation-refractory tumors that present with significant morbidity and mortality. The treatment of recurrent tumors is based on radiotherapy and repeated surgery. Systematic therapies are not effective in general but several clinical trials are ongoing. Expert commentary: Molecular characterization of the tumors, based on genetic mutations such as NF2, SMO, TERT, TRAF7, and on the methylation profile are developing, completing the histological classification and giving new insights into prognosis and treatment options.
Full Text Available Michel BilliardDepartment of Neurology, Gui de Chauliac Hospital, Montpellier, FranceAbstract: The management of narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1 Two tendencies characterize the conventional treatment of narcolepsy. Modafinil has replaced methylphenidate and amphetamine as the first-line treatment of excessive daytime sleepiness (EDS and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of modafinil, but on no direct comparison of modafinil versus traditional stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new antidepressants tend to replace tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2 The conventional treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good efficacy and is active on all symptoms of narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3 A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy.Keywords: narcolepsy, treatment, conventional drugs, modafinil, sodium oxybate, future treatments
Kantak, Kathleen M
Drug addiction is a chronically relapsing brain disorder. There is an urgent need for new treatment options for this disease because the relapse rate among drug abusers seeking treatment is quite high. During the past decade, many groups have explored the feasibility of using vaccines directed against drugs of abuse as a means of eliminating illicit drug use as well as drug overdose and neurotoxicity. Vaccines work by inducing drug-specific antibodies in the bloodstream that bind to the drug of abuse and prevent its entry into the brain. The majority of work in this area has been conducted with vaccines and antibodies directed against cocaine and nicotine. On the basis of preclinical work, vaccines for cocaine and nicotine are now in clinical trials because they can offer long-term protection with minimal treatment compliance. In addition, vaccines and antibodies for phencyclidine, methamphetamine and heroin abuse are currently under development. An underlying theme in this research is the need for high concentrations of circulating drug-specific antibodies to reduce drug-seeking and drug-taking behaviour when the drug is repeatedly available, especially in high doses. Although vaccines against drugs of abuse may become a viable treatment option, there are several drawbacks that need to be considered. These include: a lack of protection against a structurally dissimilar drug that produces the same effects as the drug of choice;a lack of an effect on drug craving that predisposes an addict to relapse; and tremendous individual variability in antibody formation. Forced or coerced vaccination is not likely to work from a scientific perspective, and also carries serious legal and ethical concerns. All things considered, vaccination against a drug of abuse is likely to work best with individuals who are highly motivated to quit using drugs altogether and as part of a comprehensive treatment programme. As such, the medical treatment of drug abuse will not be radically
van der Heyden, M A G; Stary-Weinzinger, A; Sanchez-Chapula, J A
Cardiac inward rectifier channels belong to three different classes of the KIR channel protein family. The KIR2.x proteins generate the classical inward rectifier current, IK1, while KIR3 and KIR6 members are responsible for the acetylcholine responsive and ATP sensitive inward rectifier currents IKAch and IKATP, respectively. Aberrant function of these channels has been correlated with severe cardiac arrhythmias, indicating their significant contribution to normal cardiac electrophysiology. A common feature of inward rectifier channels is their dependence on the lipid phosphatidyl-4,5-bisphospate (PIP2) interaction for functional activity. Cationic amphiphilic drugs (CADs) are one of the largest classes of pharmaceutical compounds. Several widely used CADs have been associated with inward rectifier current disturbances, and recent evidence points to interference of the channel-PIP2 interaction as the underlying mechanism of action. Here, we will review how six of these well known drugs, used for treatment in various different conditions, interfere in cardiac inward rectifier functioning. In contrast, KIR channel inhibition by the anionic anesthetic thiopental is achieved by a different mechanism of channel-PIP2 interference. We will discuss the latest basic science insights of functional inward rectifier current characteristics, recently derived KIR channel structures and specific PIP2-receptor interactions at the molecular level and provide insight in how these drugs interfere in the structure-function relationships.
The management of narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1) Two tendencies characterize the conventional treatment of narcolepsy. Modafinil has replaced methylphenidate and amphetamine as the first-line treatment of excessive daytime sleepiness (EDS) and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of modafinil, but on no direct comparison of modafinil versus traditional stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new antidepressants tend to replace tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2) The conventional treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good efficacy and is active on all symptoms of narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3) A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy. PMID:18830438
Cheng, Xiao-Qing; Pang, Lin; Cao, Xiao-Bin; Wang, Chang-He; Luo, Wei; Zhang, Bo; Wang, Hua; Li, Rong-Jian; Rou, Ke-Ming; Wu, Zun-You
To find out the current coverage of antiretroviral therapy (ART) among HIV positive subjects and to identify the major influential factors associated with the participation in ART among them. 291 HIV positive subjects from 6 methadone maintenance treatment (MMT) clinics in Guangxi and Yunnan province were surveyed by questionnaires. 217 males (74.6%) and 74 females (25.4%) were under investigation, with the average age of 38.4 +/- 5.9. Most of them received less than senior high school education, married and unemployed. Results from the single factor logistic regression analysis showed that: working status, living alone, self-reported history of drinking alcohol in the last month, negative attitude towards MMT among family members,poor self-reported compliance to MMT in the last month,lack of incentives in the MMT clinics, reluctance on disclosure of their own HIV status, good self-perception on their health status, lack of communication on ART related topics among family members in the last 6 months, lack of correct attitude and knowledge on ART etc. appeared as the main factors that influencing the participation in ART program among the patients. Data from the multivariate logistic regression analysis showed that factors as: living alone, unwilling to tell others about the status of HIV infection, poor self-perception on HIV infection, lack of discussion of ART related topics within family members in the last 6 months and poor awareness towards ART among the family members etc., were associated with the low participation rate of ART. Conclusion Strengthening the publicity and education programs on HIV positive patients and their family members at the MMT clinics seemed to be effective in extending the ART coverage. Attention should also be paid to increase the family support to the patients.
Stock, A.; Gebhardt, G.; Helle, N.; Schuettler, C.; Boegl, K.W.
It may be necessary to reduce microbiological contamination of crude drugs (medicinal plants or their parts like roots, leaves, flowers). This can be done by treating the drugs with ionizing radiation. Meethods for detection of such an irradiation were developed. It could be pointed out that measurements of luminescence, viscosity and electron spin resonance were suitable for specific drugs, but not for all drugs. (orig.) [de
Obesity in our country is a growing concern. There are several different options for weight loss; however, individuals must be self-motivated and amendable to change in order to achieve success with their weight loss goals. Several strategies used by professionals in the US today to treat overweight and obesity, include diet therapy, exercise, behavior modification, pharmacotherapy, and surgery. The focus of the American Dietetic Association (ADA) Weight Management Position Statement is no longer just on weight loss but now on weight management. Reaching one's ideal body weight is recommended but not often realistic. Frequently, the goal of treatment shifts to maintenance of ones current weight or attempts at moderate weight loss. Lifestyle modification or behavioral modification interventions rely on analyzing behavior to identify events that are associated with appropriate vs. inappropriate eating, exercise, or thinking habits. Certain primary strategies that have been found to be useful for helping people change their behaviors so that they can lose weight and maintain their weight loss, include self-monitoring, stimulus control, cognitive restructuring, stress management, social support, physical activity, and relapse prevention. Weight loss programs should strive to combine a nutritionally balanced dietary regimen with exercise and lifestyle modifications at the lowest possible cost. There are several different methods used for dietary modifications; low calorie diets, very low calorie diets, fasting, formula diets and meal replacement programs, and popular diets. Bariatric surgery is gaining popularity as it has been an effective way to treat obesity. Following gastric bypass surgery, the patients must be prepared to modify their eating behaviors and dietary selections to assist with weight loss and prevent potential complications. Patients should be educated on the dietary guidelines extensively prior to surgery and again post-operatively.
Gadó, Klára; Kocsis, Eszter; Zelkó, Romána; Hankó, Balázs; Kovácsné Balogh, Judit; Forczig, Mónika; Domján, Gyula
Despite several therapeutic possibilities the morbidity and mortality of thromboembolic disorders remain high. Improving drug compliance - i. e. keeping up the doctor's prescriptions - may be an effective tool to reach better results. To improve patients' compliance, the risk factors of non-compliance should be recognized. Among these patients' fear of adverse effects of drugs, their lack of knowledge about their illness and medication, forgetfulness, and other social, economic factors may be the most important. Furthermore, adherence may be worsened when the patient feels that the decision has been made over his/her head. Sustained medical adherence is important because anticoagulation may be a life-long treatment. The new oral anticoagulants make the matter of compliance to be current. These new type of drugs do not need regular laboratory monitoring and, therefore, compliance cannot be strictly followed. There are several studies concerning drug compliance to anticoagulant medications. Improvement of adherence is based on regular patient education after reviewing the factors of non-compliance, which needs teamwork with important roles of doctors, pharmacists, dietetics and nurses. Careful and accurate work of the participants of primary care might be complemented by the activity of anticoagulant clinics.
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
Alday, P Holland; Doggett, Joseph Stone
Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis.
Tomioka, Haruaki; Namba, Kenji
Worldwide, tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death. One-third of the world's population is infected with Mycobacterium tuberculosis (MTB), the etiologic agent of TB. The World Health Organization estimates that about eight to ten million new TB cases occur annually worldwide and the incidence of TB is currently increasing. In this context, TB is in the top three, with malaria and HIV being the leading causes of death from a single infectious agent, and approximately two million deaths are attributable to TB annually. In particular, pulmonary TB, the most common form of TB, is a highly contagious and life-threatening infection. Moreover, enhanced susceptibility to TB in HIV-infected populations is another serious health problem throughout the world. In addition, multidrug-resistant TB (MDR-TB) has been increasing in incidence in many areas, not only in developing countries but industrialized countries as well, during the past decade. These situations, particularly the global resurgence of TB and the rapid emergence of MDR-TB, underscore the importance of the development of new antituberculous drugs and new protocols for efficacious clinical control of TB patients using ordinary antimycobacterial drugs. Concerning the development of new antituberculous drugs, the following points are of particular importance. (1) Development of drugs which display lasting antimycobacterial activity in vivo is desirable, since they can be administered with long intervals and consequently facilitate directly observed therapy and enhance patient compliance. (2) Development of novel antituberculosis compounds to combat MDR-TB is urgently needed. (3) The eradication of slowly metabolizing and, if possible, dormant populations of MTB organisms that cause relapse, using new classes of anti-TB drugs is very promising for prevention of TB incidence, because it will markedly reduce the incidence of active TB from persons who are
A. N. Konovalov
Full Text Available The paper describes the classification and treatment options of craniopharyngiomas, benign epithelial tumors arising from the cell remains of the Rathke’s pouch. It presents a few types of surgical accesses during surgical treatment for this disease and gives examples of how to place an Ommaya reservoir.
Nguyen, Thuy Trang; Giau, Vo Van; Vo, Tuong Kha
Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the disadvantages of current pharmaceutical dosage options for this chronic disorder. They could have different strengths, such as offering a stable diffusion of active substance, avoiding the first pass metabolism, and reducing system adverse reactions. This article reviews the technical principles, novel techniques of transdermal delivery drug, and prospects for future development for the management of cognitive and behavioral dysfunctions in AD patients. PMID:28706327
Nguyen, Thuy Trang; Giau, Vo Van; Vo, Tuong Kha
Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the disadvantages of current pharmaceutical dosage options for this chronic disorder. They could have different strengths, such as offering a stable diffusion of active substance, avoiding the first pass metabolism, and reducing system adverse reactions. This article reviews the technical principles, novel techniques of transdermal delivery drug, and prospects for future development for the management of cognitive and behavioral dysfunctions in AD patients.
Texas, USA, where alcohol was found to be the primary drug of abuse in ... distributed among inpatients at 2 selected treatment centres ... group participants attributed their reasons for drug use to family ... NW provinces, where one currently finds limited data. .... full-time, 26% were unemployed, and 25% were students.
... treatment within the criminal justice system. Players in that policy game focused, as we are doing today, on the need to provide criminal offenders with drug abuse treatment as an alternative to incarceration...
Zorzoli, Ermanno; Marino, Maria Giulia; Bagnato, Barbara; Franco, Elisabetta
The treatment of drug addiction is a very wide-ranging sector within modern medicine. The use of immunotherapy in this context represents an innovative approach. The purpose of this paper is to illustrate, through a literature review, the main avenues of research and the results obtained with immunotherapy in the treatment of drug addiction.
Yulia Leonidovna Korsakova
Full Text Available Paget's disease is a chronic local bone disease included into a group of metabolic osteopathies in which rearrangement foci emerge in one or several bones. The disease is characterized by the appearance of ostealgia, skeletal deformity, or, for example, hearing loss occurring with skull lesion or hip or knee arthrosis and, less frequently, sarcoma or giant cell tumor. There is evidence that bisphosphonates may control the activity of Paget's disease as they inhibit the function of osteoclasts. The use of these drugs reduces the intensity of osteoalgia and the level of biochemical markers for bone resorption and osteogenesis and can decelerate or reverse the early osteolytic phase of the disease. It is promising to use of zolendronic acid (Aclasta, 5 mg, a new heterocyclic amino-containing bisphosphonate that has a significantly higher efficacy than previously used antiresorptive agents.
’ (story content) and ‘the hows’ (storying process) the article presents four findings: (1) stories of change function locally as an institutional requirement; (2) professional drug treatment providers edit young people's storytelling through different techniques; (3) the narrative environment of the drug...... treatment. Building on the sociology of storytelling and ethnographic fieldwork conducted at two drug treatment institutions for young people in Denmark, this article argues that studying stories in the context of their telling brings forth novel insights. Through a narrative analysis of both ‘the whats...... treatment institution shapes how particular stories make sense of the past, present and future; and (4) storytelling in drug treatment is an interactive achievement. A fine-grained analysis illuminates in particular how some stories on gender and drug use are silenced, while others are encouraged...
Full Text Available Sophie M WorobecDepartment of Dermatology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USAAbstract: This review surveys current treatments and future treatment trends in leprosy from a clinical perspective. The World Health Organization provides a multidrug treatment regimen that targets the Mycobacterium leprae bacillus which causes leprosy. Several investigational drugs are available for the treatment of drug-resistant M. leprae. Future directions in leprosy treatment will focus on: the molecular signaling mechanism M. leprae uses to avoid triggering an immune response; prospective studies of the side effects experienced during multiple-drug therapy; recognition of relapse rates post-completion of designated treatments; combating multidrug resistance; vaccine development; development of new diagnostic tests; and the implications of the recent discovery of a genetically distinct leprosy-causing bacillus, Mycobacterium lepromatosis.Keywords: epidemiology, leprosy, Hansen’s disease, multidrug resistance, multidrug therapy
Gangadharappa, H V; Gupta, N Vishal; Prasad M, Sarat Chandra; Shivakumar, H G
Microsponge is a microscopic sphere capable of absorbing skin secretions, therefore reducing the oiliness of the skin. Microsponge having particle size of 10-25 microns in diameter, have wide range of entrapment of various ingredients in a single microsponges system and release them at desired rates. Conventional topical preparations have various disadvantages due to irritancy, odour, greasiness and patient compliance. In many topical dosage forms fail to reach the systemic circulation in sufficient amounts in few cases. These problems overcome by the usage of formulation as microsponge in the areas of research. Drug release in microsponge is done by the external stimuli like pH, temperature and rubbing. It has several advantageous over the other topical preparations in being non-allergenic, non-toxic, non-irritant and non- mutagenic. These microsponges are used in the sun screens, creams, ointments, over-the-counter skin care preparations, recently nanosponge were reported in literature used in delivery of drug by the use of cyclodextrins to enhance the solubility of poorly water soluble drugs, which are meant for topical application.
... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...
Garcia Rodriguez, Oscar
Surgical treatment of vesicular lithiasis has changed in past years. The addition of the new techniques in daily medical practice not always is immediate. Reasons relative to when to operate a patient presenting with gall bladder calculi are argued and documenting how this procedure is mainly reserved for symptomatic patients where pain is considered as a symptom par excellence. Also, it is exposed how this change has been faced. (author)
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
Parikh, A O
Diabetes causes greater decline in physical and functional status in elderly diabetic than in a younger one. Also the rise of MI, stroke and hypertension is also higher. In elderly diabetics management is always on challenging task due to atypical disease presentation, classical symptoms often absent, presence of other coexisting conditions delays the diagnosis, dietary advice not followed properly and due to non-compliance of drug therapy. The antidiabetic drugs which are often used are: sulfonylureas, metformin, thiazolidinediones, meglitinides, alpha-glucosidase inhibitors, insulin. Advantages and disadvantages of these drugs are discussed in a nutshell. Moreover control of hypertension, CAD risk reduction and practice pearls eg, lifestyle changes and goals setting for HbA(1c) are important.
Champeau, Mathilde; Thomassin, Jean-Michel; Tassaing, Thierry; Jérôme, Christine
Drug-eluting sutures represent the next generation of surgical sutures since they fulfill their mechanical functions but also deliver the drug in their vicinity after implantation. These implants are produced by a variety of manufacturing processes. Drug-eluting sutures represent the next generation of surgical sutures since they fulfill their mechanical functions but also deliver the drug in their vicinity after implantation. These implants are produced by a variety of manufacturing processes. Two general approaches can be followed: (i) the ones that add the API into the material during the manufacturing process of the suture and (ii) the ones that load the API to an already manufactured suture. Areas covered: This review provides an overview of the current manufacturing processes for drug-eluting suture production and discusses their benefits and drawbacks depending on the type of drugs. The mechanical properties and the drug delivery profile of drug-eluting sutures are highlighted since these implants must fulfill both criteria. Expert opinion: For limited drug contents, melt extrusion and electrospinning are the emerging processes since the drug is added during the suture manufacture process. Advantageously, the drug release profile can be tuned by controlling the processing parameters specific to each process and the composition of the drug-containing polymer. If high drug content is targeted, the coating or grafting of a drug layer on a pre-manufactured suture allows for preservation of the tensile strength requirements of the suture.
Treatment with highly active antiretroviral therapy (HAART) has improved the prognosis of patients with AIDS, but it has also increased the incidence of various metabolic disorders, in particular insulin resistance accompanied by dyslipidaemia, hyperglycaemia and lipodystrophy. This is often accompanied by frank type 2 ...
Alcántara Montero, A; Sánchez Carnerero, C I
Many women will likely experience a sexual problem in their lifetime. Female sexual dysfunction is a broad term used to describe 3 categories of disorders of a multifactorial nature. Effective, but limited pharmacotherapeutic options exist to address female sexual dysfunction. The FDA recently approved the first agent for treatment of hypoactive sexual desire disorder in pre-menopausal women. Off-label use of hormonal therapies, particularly oestrogen and testosterone, are the most widely employed for female sexual dysfunction, particularly in post-menopausal women. Other drugs currently under investigation include phosphodiesterase inhibitors and agents that modulate dopamine or melanocortin receptors. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.
Weisberg, S C; Kaiser, H B
Therapy for bronchial asthma should be preventive when possible. Around-the-clock treatment with theophylline is a new way of using an old drug. Beta2-adrenergic receptor stimulators, cromolyn sodium, and steroids in aerosol form are new drugs that are useful in treatment of asthma. The good news with respect to drug treatment of asthma is that in addition to the old reliable medications which have provided good relief-including epinephrine, ephedrine, isoproterenol, aminophylline, and steroids given orally and parenterally-new drugs are available which have been extremely helpful in controlling symptoms in many patients. The bad news is that none of the new agents is a panacea and that many of them have significant undesirable side effects. It is the physician's responsibility to be wary of the new drugs for asthma and to use them appropriately.
Licht, R W; Vestergaard, P; Kessing, L V
A subcommittee under the Danish Psychiatric Association and the Child and Adolescent Psychiatric Association in Denmark have recently developed national guidelines for the psychopharmacological treatment with lithium and antiepileptic drugs, and the present translation aims at contributing...... to the international discussion on the development of proper guidelines for the treatment of bipolar disorder. Among the antiepileptic drugs, the report deals with valproate, carbamazepine and lamotrigine and to a lesser extent with oxcarbazepine, gabapentin and topiramate. The various drugs will be reviewed......, outlining the scientific evidence for mood-stabilizing properties and discussing major side effects, the most important interactions with other drugs and practical use. Special considerations during pregnancy and lactation, during treatment of children and adolescents and during treatment of the elderly...
Kofoed, Kristian; Skov, Lone; Zachariae, Claus
, and phosphodiesterase inhibitors. We review published clinical trials, and conference abstracts presented during the last years, concerned with new drugs under development for the treatment of psoriasis. In conclusion, our psoriasis armamentarium will be filled with several new effective therapeutic options the coming...... years. We need to be aware of the limitations of drug safety data when selecting new novel treatments. Monitoring and clinical registries are still important tools....
Evaluation and optimisation of current milrinone prescribing for the treatment and prevention of low cardiac output syndrome in paediatric patients after open heart surgery using a physiology-based pharmacokinetic drug-disease model.
Milrinone is the drug of choice for the treatment and prevention of low cardiac output syndrome (LCOS) in paediatric patients after open heart surgery across Europe. Discrepancies, however, among prescribing guidance, clinical studies and practice pattern require clarification to ensure safe and effective prescribing. However, the clearance prediction equations derived from classical pharmacokinetic modelling provide limited support as they have recently failed a clinical practice evaluation. Therefore, the objective of this study was to evaluate current milrinone dosing using physiology-based pharmacokinetic (PBPK) modelling and simulation to complement the existing pharmacokinetic knowledge and propose optimised dosing regimens as a basis for improving the standard of care for paediatric patients. A PBPK drug-disease model using a population approach was developed in three steps from healthy young adults to adult patients and paediatric patients with and without LCOS after open heart surgery. Pre- and postoperative organ function values from adult and paediatric patients were collected from literature and integrated into a disease model as factorial changes from the reference values in healthy adults aged 20-40 years. The disease model was combined with the PBPK drug model and evaluated against existing pharmacokinetic data. Model robustness was assessed by parametric sensitivity analysis. In the next step, virtual patient populations were created, each with 1,000 subjects reflecting the average adult and paediatric patient characteristics with regard to age, sex, bodyweight and height. They were integrated into the PBPK drug-disease model to evaluate the effectiveness of current milrinone dosing in achieving the therapeutic target range of 100-300 ng/mL milrinone in plasma. Optimised dosing regimens were subsequently developed. The pharmacokinetics of milrinone in healthy young adults as well as adult and paediatric patients were accurately described with an
Full Text Available Ankylosing spondylitis (AS is a chronic, inflammatory, rheumatic disease that mainly affects sacroiliac joints and spine. AS predominantly occurs more often in males and typically begins in the second or third decade. The mainstay of therapy in AS are nonsteroidal anti-inflammatory drugs, which reduce inflammation and pain. Disease modifying antirheumatic drugs (DMARD did not have enough evidence to prove their effect in AS treatment. The use of DMARD may not sufficient to improve the treatment and symptoms. Currently, TNF-blockers such as, Golimumab Etanersept Adalimumab İnfliksimab have promising results in the treatment of AS. TNF-blockers improve the clinical signs and symptoms, and improve the patients’ physical function and quality of life. This manuscript is focused that Current pharmacological treatments in patients with ankylosing spondylitis.
N. A. Shostak
Full Text Available The paper shows the basic mechanisms of action of nonsteroidal antinflammatory drugs (NSAID and their classification. It considers riskfactors for NSAID gastropathy and the possibilities of its treatment, prevention in the context of modern medicine.
N. A. Shostak
Full Text Available The paper shows the basic mechanisms of action of nonsteroidal antinflammatory drugs (NSAID and their classification. It considers riskfactors for NSAID gastropathy and the possibilities of its treatment, prevention in the context of modern medicine.
Hall, Anthony K; Carlson, Marilyn R
Orphan drug legislation has been introduced in a number of countries in order to stimulate the development of treatments for rare diseases by introducing commercial incentives for companies wishing to undertake that development. In order to navigate the maze of regulatory regulations and procedures so that companies can make proper use of the orphan drug incentives, specialist knowledge is required. This article will review the current status of orphan drug development in the EU and the US, e...
Full Text Available Poisoning with tricyclic antidepressants is one of the main causes of morbidity and mortality compared to all the antidepressants. Main toxic effects are on the cardiovascular system and central nervous system and manifests itself as anticholinergic symptoms. There is no antidote known to be used in the treatment. But sodium bicarbonate treatment is effective in preventing ventricular arrhythmias and hypotension, and resolving metabolic acidosis. There are some treatments that has been used for relief of symptoms and some of them still are in research stage. The drugs that are used can be customized according to the patients symptoms. [Archives Medical Review Journal 2016; 25(4.000: 608-621
Full Text Available There is now compelling evidence that TNF receptor type II (TNFR2 is predominantly expressed on CD4+Foxp3+ regulatory T cells (Tregs and myeloid-derived suppressor cells (MDSCs, and plays a major role in the expansion and function of Tregs and MDSCs. Consequently, targeting of TNFR2 by either antagonists or agonists may represent a novel strategy in the treatment of cancer and autoimmune diseases, by downregulating or upregulating suppressor cell activity. The advance in the understanding of complex structure of TNFR2 and its binding with TNF at molecular levels offers opportunity for structure-guided drug discovery. This article reviews the current evidences regarding the decisive role of TNFR2 in immunosuppressive function of Tregs and MDSCs, and the current effort to develop novel TNFR2-targeting therapeutic agents in the treatment of cancer, autoimmune diseases, and graft-versus-host disease. To shed light on the potential TNFR2-targeting small molecules, we for the first time performed virtual screening of 400,000 natural compounds against the two TNF-binding sites, regions 3 and 4, of TNFR2. Our result showed that the top hits at region 4 had slightly higher docking energies than those at region 3. Nevertheless, free energy calculation from the TNF–TNFR2 molecular dynamics simulation revealed that the binding strength of TNF in region 3 is only one-tenth of that in region 4. This suggests that region 3 is a potentially more viable binding site to be targeted by small molecules than region 4. Therefore, the effectiveness in targeting region 3 of TNFR2 deserves further investigation.
Tepe, Gunnar; Schmehl, Joerg; Heller, Stephan; Wiesinger, Benjamin; Claussen, Claus D.; Duda, Stephan H.
Treatment of the superficial femoral artery (SFA) has been among the least effective of all endovascular procedures in terms of long-term patency. The relatively small vessel lumen, in conjunction with a high plaque burden, slow flow, and a high frequency of primary occlusions, contributes to a considerable rate of acute technical failures. Because of these technical limitations a much effort has been made during the past years. This manuscript should summarize the hopes and limitations of different approaches such as brachytherapy, cutting balloons, stents and stent grafts, drug-eluting stents, and drug-coated balloons. (orig.)
Full Text Available Sunil Sethi, Kamran Zaman, Neha Jain Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India Abstract: Mycoplasma genitalium is one of the important causes of non-gonococcal urethritis. Rising incidence and emerging antimicrobial resistance are a major concern these days. The poor clinical outcomes with doxycycline therapy led to the use of azithromycin as the primary drug of choice. Single-dose azithromycin regimen over a period of time was changed to extended regimen following studies showing better clinical cures and less risk of resistance development. However, emerging macrolide resistance, either due to transmission of resistance or drug pressure has further worsened the management of this infection. The issues of drug resistance and treatment failures also exist in cases of M. genitalium infection. At present, the emergence of multidrug-resistant (MDR M. genitalium strains is an alarming sign for its treatment and the associated public health impact due to its complications. However, newer drugs like pristinamycin, solithromycin, sitafloxacin, and others have shown a hope for the clinical cure, but need further clinical trials to optimize the therapeutic dosing schedules and formulate appropriate treatment regimens. Rampant and inappropriate use of these newer drugs will further sabotage future attempts to manage MDR strains. There is currently a need to formulate diagnostic algorithms and etiology-based treatment regimens rather than the syndromic approach, preferably using combination therapy instead of a monotherapy. Awareness about the current guidelines and recommended treatment regimens among clinicians and local practitioners is of utmost importance. Antimicrobial resistance testing and global surveillance are required to assess the efficacy of current treatment regimens and for guiding future research for the early detection and management of MDR M. genitalium infections
Full Text Available Johannes Häberle,1 Shawn E McCandless2 1Division of Metabolism and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland; 2Center for Human Genetics, University Hospitals Case Medical Center, and Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA Abstract: The urea cycle disorders are caused by deficiency of one of the six hepatic enzymes or two transporters involved in detoxification of ammonia. The resulting hyperammonemia causes severe brain injury unless aggressive steps are taken to reduce the accumulation of ammonia, which is thought to be the most toxic metabolite. This review describes the current state of chronic management of urea cycle disorders, focusing on new and emerging therapies. Management strategies include the mainstay of treatment, namely dietary protein restriction and supplementation with l-arginine or l-citrulline. Several currently approved medications utilize and enhance alternative pathways of waste nitrogen excretion (sodium benzoate, sodium phenylacetate, sodium phenylbutyrate in several formulations, and glycerol phenylbutyrate, working through conjugation of the drug to either glycine (in the case of benzoate or glutamine, the products of which are excreted in the urine. Carglumic acid activates the first committed step of conversion of ammonia to urea, carbamoylphosphate synthetase, and thus effectively treats defective synthesis of the endogenous activator, N-acetylglutamate, whether due to genetic defects or biochemical inhibition of the N-acetylglutamate synthase enzyme. Approaches to neuroprotection during episodes of hyperammonemia are discussed, including the use of controlled hypothermia (brain cooling, as well as proposed, but as yet untested, pharmacologic therapies. Finally, cell-based therapies, including liver transplantation, infusion of fresh or cryopreserved hepatocytes, use of stem cells, and new approaches to gene
N-Acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision: glare sensitivity, cataract amelioration and quality of vision currently available treatment for the challenging 50,000-patient population.
Babizhayev, Mark A; Burke, Leslie; Micans, Philip; Richer, Stuart P
patients' compliance rate to self-administer NAC eye-drops. The ophthalmic drug showed potential for the non-surgical treatment of age-related cataracts for participants after controlling for age, gender and daily activities and on a combined basis of repurchases behavior reports in more than 50,000 various cohort survivors, has been demonstrated to have a high efficacy and good tolerability for prevention and treatment of visual impairment determined for the older population with relative stable pattern of causes for blindness and visual impairment. The mechanisms of prevention and reversal of cataracts with NAC ophthalmic drug are considered which include prevention by the intraocular released carnosine of free-radical-induced inactivation of proprietary lens antioxidant enzymes (superoxide dismutase); prevention of carbohydrate and metal-catalyzed autooxidation of ascorbic acid-induced cross-linking glycation reactions to the lens proteins; transglycation properties of carnosine, allowing it to compete for the glycating agent, protecting proteins (lens crystallins) against modification; universal antioxidant and scavenging activity towards lipid hydroperoxides, aldehydes and oxygen radicals; activation with l-carnosine ingredient of proteasome activity in the lens; chaperone-like disaggregating to lens crystallins activity of NAC and of its bioactivated principal carnosine. Blindness incidence increased with advancing age, such as cataract and glaucoma, which are by far the commonest causes of blindness in our sample and in all age groups, glaucomatous neurodegeneration can be treated with developed NAC autoinduction prodrug eye drops equipped with corneal absorption promoters. The common blinding affections presenting in developed countries such as, senile macular degeneration, hereditary chorioretinal dystrophies, diabetic retinopathy are poorly represented in our current summary of vital-statistics and will be reported inherent in next N-acetylcarnosine ophthalmic
N-Acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision: Glare sensitivity, cataract amelioration and quality of vision currently available treatment for the challenging 50,000-patient population
Mark A Babizhayev
with advancing age, such as cataract and glaucoma, which are by far the commonest causes of blindness in our sample and in all age groups, glaucomatous neurodegeneration can be treated with developed NAC autoinduction prodrug eye drops equipped with corneal absorption promoters. The common blinding affections presenting in developed countries such as, senile macular degeneration, hereditary chorioretinal dystrophies, diabetic retinopathy are poorly represented in our current summary of vital-statistics and will be reported inherent in next N-acetylcarnosine ophthalmic drug studies.Conclusion: The authors present evidence, about why only a certain kind of NAC is safe, and why only certain formulas designed by IVP for drug discovery are efficacious in the prevention and treatment of senile cataract for long-term use. Overall cumulated studies demonstrate that the designed by IVP new vision-saving drug NAC eye drops help the aging eye to recover by improving its clarity, glare sensitivity, color perception and overall vision.Keywords: age-related ophthalmic diseases, cataract, disability-glare, halos, Halometer, visual-acuity, N-acetylcarnosine lubricant eye drops, repurchase behavior analysis, 50,000-patients’ compliance to self-administer eye drops
Achal Bhatt; Aminder Gill
Opioids are widely used drugs for treatment of pain and related disorders. Opiate addiction is a major public health concern in the United States causing significant increase in healthcare expenditure. They produce euphoria and sense of well-being which makes them addictive to some people. Used in higher doses they can lead to cardiac or respiratory compromise. They also impair cognition leading to impaired decision making. Opioids exert their effects by acting on three different types of re...
Filges, Trine; Andersen, Ditte; Jørgensen, Anne-Marie Klint
The main aim of this review is to evaluate the current evidence on the effects of FFT on drug abuse reduction for young people in treatment for non-opioid drug use.......The main aim of this review is to evaluate the current evidence on the effects of FFT on drug abuse reduction for young people in treatment for non-opioid drug use....
Peltzer, Karl; Ramlagan, Shandir; Johnson, Bruce D; Phaswana-Mafuya, Nancy
This review synthesizes available epidemiological data on current drug use and substance user treatment admissions in South Africa since 1994, and how changes in the political, economic, and social structures within South Africa, both before and after Apartheid, has made the country more vulnerable to drug use. Based on national surveys, current use of cannabis ranged among adolescents from 2% to 9% and among adults it was 2%, cocaine/crack (0.3%), mandrax/sedatives (0.3%), club drugs/amphetamine-type stimulants (0.2%), opiates (0.1%), and hallucinogens (0.1%). The use of primary illicit substance at admission to South African drug user treatment centers was cannabis 16.9%, methamphetamine (tik) 12.8%, crack/cocaine 9.6%, cannabis and mandrax 3.4%, heroin/opiates 9.2%, and prescription and OTC drugs 2.6%. An increase in substance user treatment admissions has increased. While the prevalence of illicit drug use in South Africa is relatively low compared to the United States and Australia, prevention and intervention policies need to be designed to reduce these levels by targeting the more risky subpopulations identified from this review.
Greberman, S B; Jasinski, D
This study was undertaken to determine differences in previous treatment patterns in individuals currently using different numbers of substances. Medical records of 1198 inpatient detoxification (detox) admissions were analyzed. Numbers of past admissions to completed detox, methadone, or other types of drug abuse treatment were totaled and ranked to determine most frequent type. Within gender, treatment histories of single and multiple drug abusers usually do not differ. The one exception is male multiple drug abusers ages 26-30, who show increased admissions. Possible explanations are that men do not seek treatment before developing medical complications of addiction or until external factors influence admission. There were differences in treatment histories between genders in multiple drug abusers only. Before age 30, women reported increased treatment of certain types. Possible explanations are that treatment priority is given to women who are, or may be, pregnant. Also, younger men may not enter or complete treatment. Previous treatment history may influence many behaviors. The results of this study delineate several valuable indicators for assessing past history.
Marcio C. Mancini
Full Text Available Obesity is a chronic disease associated with excess morbidity and mortality. Clinical treatment, however, currently offers disappointing results, with very high rates of weight loss failure or weight regain cycles, and only two drugs (orlistat and sibutramine approved for long-term use. Drugs combinations can be an option for its treatment but, although widely used in clinical practice, very few data are available in literature for its validation. Our review focuses on the rationale for their use, with advantages and disadvantages; on combinations often used, with or without studies; and on new perspectives of combinations being studied mainly by the pharmaceutical industry.
Sattar, Mohammed; Sayed, Ossama M; Lane, Majella E
Oral transmucosal drug delivery (OTDD) dosage forms have been available since the 1980s. In contrast to the number of actives currently delivered locally to the oral cavity, the number delivered as buccal or sublingual formulations remains relatively low. This is surprising in view of the advantages associated with OTDD, compared with conventional oral drug delivery. This review examines a number of aspects related to OTDD including the anatomy of the oral cavity, models currently used to study OTDD, as well as commercially available formulations and emerging technologies. The limitations of current methodologies to study OTDD are considered as well as recent publications and new approaches which have advanced our understanding of this route of drug delivery. Copyright © 2014 Elsevier B.V. All rights reserved.
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.
Veninga, CCM; Denig, P; Zwaagstra, R; Haaijer-Ruskamp, FM
In the international Drug Education Project, an educational program involving auditing and feedback in peer groups to improve the treatment of asthma and urinary tract infections (UTI) was developed and tested in primary care. Individualized feedback was provided and discussed in 24 Dutch peer
Full Text Available Helminth infections are responsible for a considerable public health burden, yet the current drug armamentarium is small. Given the high cost of drug discovery and development, the high failure rates and the long duration to develop novel treatments, drug repurposing circumvents these obstacles by finding new uses for compounds other than those they were initially intended to treat. In the present review, we summarize in vivo and clinical trial findings testing clinical candidates and marketed drugs against schistosomes, food-borne trematodes, soil-transmitted helminths, Strongyloides stercoralis, the major human filariases lymphatic filariasis and onchocerciasis, taeniasis, neurocysticercosis and echinococcosis. While expanding the applications of broad-spectrum or veterinary anthelmintics continues to fuel alternative treatment options, antimalarials, antibiotics, antiprotozoals and anticancer agents appear to be producing fruitful results as well. The trematodes and nematodes continue to be most investigated, while cestodal drug discovery will need to be accelerated. The most clinically advanced drug candidates include the artemisinins and mefloquine against schistosomiasis, tribendimidine against liver flukes, oxantel pamoate against trichuriasis, and doxycycline against filariasis. Preclinical studies indicate a handful of promising future candidates, and are beginning to elucidate the broad-spectrum activity of some currently used anthelmintics. Challenges and opportunities are further discussed.
Nordheim, W.; Braeuniger, S.; Kirsch, B.; Kotowski, H.; Teupel, D.
The concise and tabulated review reports experimental results on the effects of radiation treatment on drugs, vaccines, biochemicals and adjuvants including enzymes as well. Irradiation was mostly performed by γ-radiation using 60 Co and to a lesser extent by 137 Cs, 182 Ta, X-rays and accelerators. Ionizing radiation proved to be a useful tool for sterilization and inactivation in producing drugs, vaccines, and bioactive agents and will contribute to realize procedures difficultly solvable as to engineering and economy, respectively. 124 refs
... HIV/AIDS Treatment Antiretroviral drugs used in the treatment of HIV infection Share Tweet Linkedin Pin it More sharing ... Pin it Email Print Drugs Used in the Treatment of HIV Infection All FDA-approved medicines used in the ...
Kim, Jee Wook; Lee, Boung Chul; Kang, Tae-Cheon; Choi, Ihn-Geun
Alcoholism is becoming one of the most serious issues in Korea. The purpose of this review article was to understand the present status of the treatment system for alcoholism in Korea compared to the United States and to suggest its developmental direction in Korea. Current modalities of alcoholism treatment in Korea including withdrawal treatment, pharmacotherapy, and psychosocial treatment are available according to Korean evidence-based treatment guidelines. Benzodiazepines and supportive care including vitamin and nutritional support are mainly used to treat alcohol withdrawal in Korea. Naltrexone and acamprosate are the drugs of first choice to treat chronic alcoholism. Psychosocial treatment methods such as individual psychotherapy, group psychotherapy, family therapy, cognitive behavior therapy, cue exposure therapy, 12-step facilitation therapy, self-help group therapy, and community-based treatment have been carried out to treat chronic alcoholism in Korea. However, current alcohol treatment system in Korea is not integrative compared to that in the United States. To establish the treatment system, it is important to set up an independent governmental administration on alcohol abuse, to secure experts on alcoholism, and to conduct outpatient alcoholism treatment programs and facilities in an open system including some form of continuing care.
Dannon, Pinhas N; Lowengrub, Katherine; Gonopolski, Yehudit; Kotler, Moshe
Psychotic major depressive disorder (MDD) is a mood disorder characterized by severe affective and neurovegetative symptoms together with the presence of delusions and/or hallucinations. It is a common disorder seen in a quarter of consecutively admitted depressed patients and is often associated with severe symptomatology, increased suicide risk, poor acute response to antidepressants and poor acute and long-term treatment outcome. It is possible that poor response in psychotic depression is caused by the fact that we have yet to identify the most efficacious treatment protocol for psychotic MDD. Multiple studies have shown that modifications in the treatment paradigm may increase treatment efficacy in psychotic MDD. It has been generally accepted that, during the acute treatment phase, antidepressant-antipsychotic drug combination therapy is more effective than either treatment alone, although this strategy has recently been challenged. The question of the optimal duration of pharmacotherapy in order to prevent relapse and improve long-term (i.e., 5-year) outcome is a focus of current investigation. This article will review currently recommended treatment strategies for the acute, continuation and maintenance phases of therapy. In particular, it will address the role of newer-generation antidepressants, the role of second-generation antipsychotics, the use of mood stabilizers and indications for electroconvulsive therapy. Other possible treatment strategies such as transcranial magnetic stimulation, vagus nerve stimulation, deep-brain stimulation and glucocorticoid receptor antagonists will be discussed. Current recommendations for the prevention of relapse and improvement of long-term outcome will be reviewed.
Pedersen, Christina Louise; Romner, Bertil
Through a comprehensive review of the current literature, the present article investigates several aspects of low grade astrocytomas (LGA), including prognostic factors, treatment strategies and follow-up regimes. LGA are in general relatively slow-growing primary brain tumours, but they have a v...... effective in discriminating between tumour progression and radiation necrosis. The research into biomarkers is currently limited with regards to their applications in LGA diagnostics, and therefore further studies including larger patient populations are needed.......Through a comprehensive review of the current literature, the present article investigates several aspects of low grade astrocytomas (LGA), including prognostic factors, treatment strategies and follow-up regimes. LGA are in general relatively slow-growing primary brain tumours, but they have...... as the course of disease. The current literature seems to support the idea that treatment with radical tumour resection, where possible, yields better long term outcome for patients with LGA. However, adjuvant therapy is often necessary. Administering early postoperative radiotherapy to patients with partially...
Full Text Available Cardiac arrest is defined as the sudden cessation of spontaneous ventilation and circulation. Within 15 seconds of cardiac arrest, the patient loses consciousness, electroencephalogram becomes flat after 30 seconds, pupils dilate fully after 60 seconds, and cerebral damage takes place within 90–300 seconds. It is essential to act immediately as irreversible damage can occur in a short time. Cardiopulmonary resuscitation (CPR is an attempt to restore spontaneous circulation through a broad range of interventions which are early defibrillation, high-quality and uninterrupted chest compressions, advanced airway interventions, and pharmacological interventions. Drugs should be considered only after initial shocks have been delivered (when indicated and chest compressions and ventilation have been started. During cardiopulmonary resuscitation, no specific drug therapy has been shown to improve survival to hospital discharge after cardiac arrest, and only few drugs have a proven benefit for short-term survival. This paper reviews current pharmacological treatment of cardiac arrest. There are three groups of drugs relevant to the management of cardiac arrest: vasopressors, antiarrhythmics, and other drugs such as sodium bicarbonate, calcium, magnesium, atropine, fibrinolytic drugs, and corticosteroids.
... more) drugs or between a drug and a food or beverage. Taking a drug while having certain medical conditions ... interaction : A reaction between a drug and a food or beverage. Drug-condition interaction : A reaction that occurs when ...
Full Text Available Atrial fibrillation (AF is the most common sustained arrhythmia encountered in clinical practice. Its incidence increases with age. AF is classified into subtypes according to the duration and/or able to provide sinus rhytym. İnitially, patients should be evaluated for rhythm or rate control for appropriate treatment. Second stage of strategy aimed to investigate the feasibility of anticoagulation therapy. Recently, due to the progress made in treatment with rhythm control and anticoagulation therapy, either American or European guidelines have been renovated. These developments have taken place in the newly published guide. In this article, the current change in the management of AF is discussed.
Harpreet Singh Sidhu
Full Text Available Antiepileptic drugs (AEDs are extensively used worldwide to treat a wide range of disorders other than epilepsy, such as neuropathic pain, migraine and bipolar disorder. Due to this situation more than 20 new third-generation AEDs have been introduced in the market recently. The future design of new AEDs must also have potential to help in the non-epileptic disorders. The wide acceptance of second generation AEDs for the management of various Non-epileptic disorders has caused the emergence of generics in the market. The wide use of approved AEDs outside epilepsy is based on both economic and scientific reasons. Bipolar disorders, migraine prophylaxis, fibromyalgia and neuropathic pain represent the most attractive indication expansion opportunities for anticonvulsant developers, providing blockbuster revenues. Strong growth in non-epilepsy conditions will see Pfizer’s Lyrica become the market leading brand by 2018. In this review we mainly focus on the current status of new AEDs in the treatment of chronic pain and migraine prophylaxis. AEDs have a strong analgesic potential and this is demonstrated by the wide use of carbamazepine in trigeminal neuralgia and sodium valproate in migraine prophylaxis. At present, data on the new AEDs for non-epileptic conditions are inconclusive. Not all AEDs are effective in the management of neuropathic pain and migraine. Only those AEDs whose mechanisms of action are match with pathophysiology of the disease, have potential to show efficacy in non-epileptic disorder. For this better understanding of the pathophysiology of the disease and mechanisms of action of new AEDs are essential requirement before initiating pre-clinical and clinical trials. Many new AEDs show good results in the animal model and open-label studies but fail to provide strong evidence at randomized, placebo-controlled trials. The final decision regarding the clinical efficacy of the particular AEDs in a specific non-epileptic disorder
Full Text Available The study was conducted on 190 milk samples of bovine mastitis and 138 samples were confirmed positives for microorganisms. All the 138 samples were subjected to drug sensitivity test. The most effective antibiotic was enrofloxacin (91.67% followed by ciprofloxacin (90.15%, amikacin (87.12%, ceftriaxone (84.10%, chloramphenicol (80.31%, cefotaxime (79.55% and gentamicin (77.27%. Microorganisms were mostly resistant to drugs like streptomycin, penicillinG, ampicillin, cloxacillin, amoxycillin and neomycin in increasing order of resistance. Hence, it is suggested that the line of treatment should be based on antibiogram study of various isolates from bovine mastitis. Further, the selection of drugs after culture and sensitivity test should be based on their ability to cross blood tissue barrier or mammary parenchyma, lipophilicity and ability to work in alkaline pH. [Vet. World 2010; 3(1.000: 17-20
Yasgar, Adam; Simeonov, Anton
Much has been presented and debated on the topic of drug abuse and its multidimensional nature, including the role of society and its customs and laws, economical factors, and the magnitude and nature of the burden. Given the complex nature of the receptors and pathways implicated in regulation of the cognitive and behavioral processes associated with addiction, a large number of molecular targets have been interrogated during recent years to discover starting points for development of small-molecule interventions. This review describes recent developments in the field of early drug discovery for drug abuse interventions with an emphasis on the advances published during the 2012 - 2014 period. Technologically, the processes/platforms utilized in drug abuse drug discovery are nearly identical to those used in the other disease areas. A key complicating factor in drug abuse research is the enormous biological complexity surrounding the brain processes involved and the associated difficulty in finding 'good' targets and achieving exquisite selectivity of treatment agents. While tremendous progress has been made during recent years to use the power of high-throughput technologies to discover proof-of-principle molecules for many new targets, next-generation models will be especially important in this field. Examples include: seeking advantageous drug-drug combinations, the use of automated whole-animal behavioral screening systems, advancing our understanding of the role of epigenetics in drug addiction and the employment of organoid-level 3D test platforms (also referred to as tissue-chip or organs-on-chip).
Zhu, Weili; Zhang, Yinan; Huang, Yingjie; Lu, Lin
This chapter summarizes recent developments in preclinical and clinical research on Chinese herbal medicines and their neurochemical mechanism of action for the treatment of drug addiction. We searched Chinese and English scientific literature and selected several kinds of Chinese herbal medicines that have beneficial effects on drug addiction. Ginseng (Renshen) may be clinically useful for the prevention of opioid abuse and dependence. Rhizoma Corydalis (Yanhusuo) may be used to prevent relapse to chronic drug dependence. Alkaloids of Uncaria rhynchophylla (Gouteng) appear to have positive effects on methamphetamine and ketamine addiction. Both Salvia miltiorrhiza (Danshen) and Radix Pueraiae (Gegen) have beneficial inhibitory effects on alcohol intake. Sinomenine has been shown to have preventive and curative effects on opioid dependence. l-Stepholidine, an alkaloid extract of the Chinese herb Stephania intermedia (Rulan), attenuated the acquisition, maintenance, and reacquisition of morphine-induced conditioned place preference and antagonized the heroin-induced reinstatement of heroin seeking. Traditional Chinese herbal medicines may be used to complement current treatments for drug addiction, including withdrawal and relapse. As the molecular mechanisms of action of traditional Chinese herbal medicines are elucidated, further advances in their use for the treatment of drug addiction are promising. © 2017 Elsevier Inc. All rights reserved.
Schlottmann, Francisco; Patti, Marco G
Esophageal achalasia is a primary esophageal motility disorder of unknown origin, characterized by lack of peristalsis and by incomplete or absent relaxation of the lower esophageal sphincter in response to swallowing. The goal of treatment is to eliminate the functional obstruction at the level of the gastroesophageal junction Areas covered: This comprehensive review will evaluate the current literature, illustrating the diagnostic evaluation and providing an evidence-based treatment algorithm for this disease Expert commentary: Today we have three very effective therapeutic modalities to treat patients with achalasia - pneumatic dilatation, per-oral endoscopic myotomy and laparoscopic Heller myotomy with fundoplication. Treatment should be tailored to the individual patient, in centers where a multidisciplinary approach is available. Esophageal resection should be considered as a last resort for patients who have failed prior therapeutic attempts.
Hall, Anthony K; Carlson, Marilyn R
Orphan drug legislation has been introduced in a number of countries in order to stimulate the development of treatments for rare diseases by introducing commercial incentives for companies wishing to undertake that development. In order to navigate the maze of regulatory regulations and procedures so that companies can make proper use of the orphan drug incentives, specialist knowledge is required. This article will review the current status of orphan drug development in the EU and the US, explain the incentives and procedures, and touch on the role of patient organisations in the process.
Thuy Trang Nguyen; Vo Van Giau; Tuong Kha Vo
Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the...
Çetin Kürşad Akpınar
Full Text Available Status Epilepticus (SE is a medical emergency that causes significant morbidity and mortality and requires prompt diagnosis and treatment. Although SE can be divided into two subgroups as convulsive and nonconvulsive, treatment principles are generally similar. Treatment should be prompt and underlying cause should be corrected. Although intravenous lorazepam is the first-line treatment due to a lower risk of relapse, diazepam becomes the first choice since loeazepan is not available in our country. Even though intravenous benzodiazepine stops seizures, intravenous antiepileptic drug (phenytoin, etc. should be administered at a loading dose. Patients with refractory status epilepticus should be supported with respect to vital, respiratory, metabolic and hemodynamic aspects and followed up in an intensive care unit to monitor cerebral electrical activity. The most common cause in the etiology is the cessation of antiepileptic drugs. The aim of SE treatment is to stop seizures and prevent complications and recurrence. In this paper, current diagnosis, treatment and etiology of SE are reviewed.
U.S. Department of Health & Human Services — The California Drug and Alcohol Treatment Assessment (CALDATA) was designed to study the costs, benefits, and effectiveness of the state's alcohol and drug treatment...
Filges, Trine; Rasmussen, Pernille; Andersen, Ditte
The main objectives of this review are to evaluate the current evidence on the effects of MDFT on drug abuse reduction for young people (aged 11-21 years) in treatment for non-opioid drug abuse, and if possible to examine moderators of drug abuse reduction effects, specifically analysing whether...
While the evidence for urine drug testing for patients on chronic opioid therapy is weak, the guidelines created by numerous medical societies and state and federal regulatory agencies recommend that it be included as one of the tools used to monitor patients for compliance with chronic opioid therapy. To get the most comprehensive results, clinicians should order both an immunoassay screen and confirmatory urine drug test. The immunoassay screen, which can be performed as an in-office point-of-care test or as a laboratory-based test, is a cheap and convenient study to order. Limitations of an immunoassay screen, however, include having a high threshold of detectability and only providing qualitative information about a select number of drug classes. Because of these restrictions, clinicians should understand that immunoassay screens have high false-positive and false-negative rates. Despite these limitations, though, the results can assist the clinician with making preliminary treatment decisions. In comparison, a confirmatory urine drug test, which can only be performed as a laboratory-based test, has a lower threshold of detectability and provides both qualitative and quantitative information. A urine drug test's greater degree of specificity allows for a relatively low false-negative and false-positive rate in contrast to an immunoassay screen. Like any other diagnostic test, an immunoassay screen and a confirmatory urine drug test both possess limitations. Clinicians must keep this in mind when interpreting an unexpected test result and consult with their laboratory when in doubt about the meaning of the test result to avoid making erroneous decisions that negatively impact both the patient and clinician.
Full Text Available Cryptosporidiosis emergence triggered the screening of many compounds for potential anti-cryptosporidial activity in which the majority were ineffective. The outbreak of cryptosporidiosis which occurred in Milwaukee in 1993 was not only the first significant emergence of Cryptosporidium spp. as a major human pathogen but also a huge waterborne outbreak thickening thousands of people from a major city in North America. Since then, outbreaks of cryptosporidiosis are regularly occurring throughout the world. New drugs against this parasite became consequently urgently needed. Among the most commonly used treatments against cryptosporidiosis are paromomycin, and azithromycin, which are partially effective. Nitazoxanide (NTZ’s effectiveness was demonstrated in vitro, and in vivo using several animal models and finally in clinical trials. It significantly shortened the duration of diarrhea and decreased mortality in adults and in malnourished children. NTZ is not effective without an appropriate immune response. In AIDS patients, combination therapy restoring immunity along with antimicrobial treatment of Cryptosporidium infection is necessary. Recent investigations focused on the potential of molecular-based immunotherapy against this parasite. Others tested the effects of probiotic bacteria, but were unable to demonstrate eradication of C. parvum. New synthetic isoflavone derivatives demonstrated excellent activity against C. parvum in vitro and in a gerbil model of infection. Newly synthesized nitroor non nitro- thiazolide compounds, derived from NTZ, have been recently shown to be at least as effective as NTZ against C. parvum in vitro development and are promising new therapeutic agents.
Baxevanis, Fotios; Kuiper, Jesse; Fotaki, Nikoletta
Gastric fed state conditions can have a significant effect on drug dissolution and absorption. In vitro dissolution tests with simple aqueous media cannot usually predict drugs' in vivo response, as several factors such as the meal content, the gastric emptying and possible interactions between food and drug formulations can affect drug's pharmacokinetics. Good understanding of the effect of the in vivo fed gastric conditions on the drug is essential for the development of biorelevant dissolution media simulating the gastric environment after the administration of the standard high fat meal proposed by the FDA and the EMA in bioavailability/bioequivalence (BA/BE) studies. The analysis of drugs in fed state media can be quite challenging as most analytical protocols currently employed are time consuming and labour intensive. In this review, an overview of the in vivo gastric conditions and the biorelevant media used for their in vitro simulation are described. Furthermore an analysis of the physicochemical properties of the drugs and the formulations related to food effect is given. In terms of drug analysis, the protocols currently used for the fed state media sample treatment and analysis and the analytical challenges and needs emerging for more efficient and time saving techniques for a broad spectrum of compounds are being discussed. Copyright © 2016 Elsevier B.V. All rights reserved.
Full Text Available Christina M Dieli-Conwright, Breanna Z Orozco Division of Biokinesiology and Physical Therapy, Women's Health and Exercise Laboratory, University of Southern California, Los Angeles, CA, USA Abstract: Over the past 2 decades, great strides have been made in the field of exercise-oncology research, particularly with breast cancer. This area of research is particularly important since there are >2.8 million breast cancer survivors who are in need of an intervention that can offset treatment-related side effects. Noticeable reductions in physical fitness (ie, cardiopulmonary fitness and muscular strength, negative changes in body composition (ie, increase in body mass, decrease in lean body mass, and increase in fat mass, increased fatigue, depression, or anxiety are some of the common side effects of cancer treatments that negatively impact overall quality of life and increase the risk for the development of comorbidities. Exercise plays a vital role in improving cardiopulmonary function, psychological events, muscular strength, and endurance in breast cancer survivors, and thus should be considered as a key factor of lifestyle intervention to reverse negative treatment-related side effects. The purpose of this review is to address current perspectives on the benefits of aerobic and resistance exercise after breast cancer treatments. This review is focused on the well-established benefits of exercise on physical and emotional well-being, bone health, lymphedema management, and the postulated benefits of exercise on risk reduction for recurrence of breast cancer. Keywords: breast cancer, exercise, physical well-being
John D. Isaacs
Full Text Available Three biosimilar products are now licensed for the treatment of rheumatic diseases in Europe. The European Medicines Agency (EMA requires that similarity between a biosimilar and its reference product is demonstrated using a rigorous, stepwise process that includes extensive physicochemical and biological analytical testing, non-clinical pharmacology, clinical evaluations, and pharmacovigilance plans. Each step is highly sensitive to any differences between products and progressively reduces any uncertainty over similarity; all steps must be satisfied to demonstrate biosimilarity. The US Food and Drug Administration (FDA requires a similar stringent biosimilar development process. The etanercept biosimilar SB4 (Benepali®, recently approved for the treatment of rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis (ankylosing spondylitis, non-radiographic axial spondyloarthritis, and plaque psoriasis, is herein used to demonstrate the detailed analytical characterisation and clinical testing that are required by the EMA before biosimilars are approved for use. A comprehensive characterisation study involving >55 physiochemical and >25 biological assays demonstrated that SB4 has highly similar structural, physicochemical, and biological quality attributes to reference etanercept. A Phase I study demonstrated pharmacokinetic equivalence between SB4 and reference etanercept in healthy male subjects. Furthermore, a Phase III, randomised, controlled trial performed in patients with moderate-to-severe rheumatoid arthritis despite treatment with methotrexate (MTX showed that SB4 was equivalent to etanercept in terms of efficacy, safety, and immunogenicity. In conclusion, the biosimilar development process performed according to EMA or FDA guidelines is highly rigorous and comprehensive. Biosimilars such as SB4 are now available in clinical practice and are likely to improve access, reduce costs, and ultimately, improve health outcomes.
Full Text Available Abstract Background Opiates are the main drugs of abuse, and Methadone Maintenance Treatment (MMT is the most widely administered drug addiction treatment program in Iran. Our study aimed to investigate patterns of pre-treatment drug abuse, addiction treatment history and characteristics of patients in MMT in Tehran. Methods We applied a stratified cluster random sampling technique and conducted a cross-sectional survey utilizing a standard patient characteristic and addiction history form with patients (n = 810 in MMT. The Chi-square test and t-test served for statistical analyses. Results A clear majority of the participants were men (96%, more than 60% of whom were between 25 and 44 years of age, educated (89% had more than elementary education, and employed (>70%. The most commonly reported main drugs of abuse prior to MMT entry were opium (69% and crystalline heroin (24%. The patients’ lifetime drug experience included opium (92%, crystalline heroin (28%, cannabis (16%, amphetamines (15%, and other drugs (33%. Crystalline heroin abusers were younger than opium users, had begun abusing drugs earlier, and reported a shorter history of opiate addiction. Conclusion Opium and crystalline heroin were the main drugs of abuse. A high rate of addiction using more dangerous opiate drugs such as crystalline heroin calls for more preventive efforts, especially among young men.
Background Opiates are the main drugs of abuse, and Methadone Maintenance Treatment (MMT) is the most widely administered drug addiction treatment program in Iran. Our study aimed to investigate patterns of pre-treatment drug abuse, addiction treatment history and characteristics of patients in MMT in Tehran. Methods We applied a stratified cluster random sampling technique and conducted a cross-sectional survey utilizing a standard patient characteristic and addiction history form with patients (n = 810) in MMT. The Chi-square test and t-test served for statistical analyses. Results A clear majority of the participants were men (96%), more than 60% of whom were between 25 and 44 years of age, educated (89% had more than elementary education), and employed (>70%). The most commonly reported main drugs of abuse prior to MMT entry were opium (69%) and crystalline heroin (24%). The patients’ lifetime drug experience included opium (92%), crystalline heroin (28%), cannabis (16%), amphetamines (15%), and other drugs (33%). Crystalline heroin abusers were younger than opium users, had begun abusing drugs earlier, and reported a shorter history of opiate addiction. Conclusion Opium and crystalline heroin were the main drugs of abuse. A high rate of addiction using more dangerous opiate drugs such as crystalline heroin calls for more preventive efforts, especially among young men. PMID:22676557
Fibromyalgia (FM) is a common, complex chronic widespread pain condition is characterized by fatigue, sleep disturbance and cognitive dysfunction. Treatment of FM is difficult, requiring both pharmacological and non-pharmacological approaches, with an empiric approach to drug therapy focused toward individual symptoms, particularly pain. The effectiveness of current medications is limited with many patients discontinuing use. A systemic database search has identified 26 molecular entities as potential emerging drug therapies. Advances in the understanding of the pathophysiology of FM provides clues to targets for new medications. Investigation of bioamine modulation and α2δ ligands and novel targets such as dopamine receptors, NMDA receptors, cannabinoid receptors, melatonin receptors and potassium channels has identified potential drug therapies. Modest improvement of health status in patients with FM has been observed with drugs targeting a diverse range of molecular mechanisms. No single drug, however, offered substantial efficacy against all the symptoms characteristic of FM. Identification of new and improved therapies for FM needs to address the heterogeneity of the condition, which suggests existence of patient subgroups, the relationship of central and peripheral aspects of the pathophysiology and a requirement of combination therapy with drugs targeting multiple molecular mechanisms.
Full Text Available The perspectives in the pharmacological treatment of obesitycan be classified in two classes: drugs already in the market,in advanced clinical trial or in final approval, or drugs in earlydevelopment. Among the first class are antiepileptic drugslike topiramate (although it was studied for obesity treatmentit was descontinued for this indication because of the highdrop-out rate in clinical trials and zonisamide (with someshort term studies in obese adults; antidepressives likebupropion (that leads to weight reduction and also diminishesthe weight gain associated to smoking cessation andradafaxine (a bupropion metabolite, without reported trials inobese subjects; glucagon-like peptide-1 analogues like exenatide(exendin-4, pramlintide and liraglutide (with studiesin type 2 diabetic obese subjects and the selective blockerof the cannabinoid-1 receptor, rimonabant, with a large bodyof studies (Rimonabant in Obesity, RIO-Europe, RIO-NorthAmerica, RIO-Lipids and RIO-Diabetes, involving more than6.600 patients with obesity, with and without diabetes, beingan important perspective of treatment for obesity andmetabolic syndrome. In early phase of development, we canreport some energy balance modulators like neuropeptide Yantagonists, melanocortin agonists, leptine and its analoguesand ciliary neurotrophic factor (axokine; termogenic agentslike agonists of the beta-3 adrenergic receptor, uncouplingagents of the mithocondrial membrane and peripheralmodulators of the energy balance (cholecystokinine.
Sonoda, Yukihiko; Kumabe, Toshihiro; Saito, Ryuta; Kanamori, Masayuki; Yamashita, Yoji; Tominaga, Teiji
In this paper, we selected three representative disorders among pediatric gliomas and reviewed standard treatments for these diseases. The formation of this rare disease is involved with BRAF mutation as well as cerebellar pilocytic astrocytoma. Radical resection is not recommended as initial therapy due to high morbidity. Despite its good tumor control, radiotherapy is not a standard therapy due to neuroendocrine and neurocognitive dysfunction. Several papers have reported the effectiveness of platinum-based chemotherapy, which is a useful for induction therapy. Recent progress in molecular analyses has suggested that some markers might be used for staging ependymoma. While total resection is considered to be strongly correlated with patients' survival, the majority of recurrence occurs in the primary site. Despite many clinical trials, chemotherapeutic agents were not found to be effective for this disease. Since whole brain radiation cannot prevent dissemination, local radiation is recommended for adjuvant therapy. The prognosis of this disease is still dismal, and median survival time is within 1 year. Although clinical trials have been conducted to assess the efficacy of chemotherapy prior to, concomitantly with, or after radiotherapy, an effective regimen has not yet been established. Therefore, only conventional local radiotherapy is the standard regimen for this disease. A new therapeutic approach, such as convection-enhanced drug delivery, would be required for improved outcomes in patients with this disease. (author)
Comerma Steffensen, Simon Gabriel; Grann, Martin; Andersen, Charlotte U
cardiovascular risk, while an inverse agonist at cannabinoid type 1 (CB1) receptors, rimonobant was withdrawn due to serious psychiatric problems. At present there are only few treatments available including orlistat and, phentermine alone or in combination with topiramate and lorcaserin, although cardiovascular...... side effects need to be clarified regarding phentermine and lorcaserin. Drugs approved for type 2 diabetes including glucagon like peptide (GLP-1) analogues and metformin also cause moderate weight losses and have a favourable cardiovascular profile, while the anti-obesity potential of nebivolol...
Kim, Munju; Gillies, Robert J; Rejniak, Katarzyna A
Delivery of anti-cancer drugs to tumor tissues, including their interstitial transport and cellular uptake, is a complex process involving various biochemical, mechanical, and biophysical factors. Mathematical modeling provides a means through which to understand this complexity better, as well as to examine interactions between contributing components in a systematic way via computational simulations and quantitative analyses. In this review, we present the current state of mathematical modeling approaches that address phenomena related to drug delivery. We describe how various types of models were used to predict spatio-temporal distributions of drugs within the tumor tissue, to simulate different ways to overcome barriers to drug transport, or to optimize treatment schedules. Finally, we discuss how integration of mathematical modeling with experimental or clinical data can provide better tools to understand the drug delivery process, in particular to examine the specific tissue- or compound-related factors that limit drug penetration through tumors. Such tools will be important in designing new chemotherapy targets and optimal treatment strategies, as well as in developing non-invasive diagnosis to monitor treatment response and detect tumor recurrence.
.... In 1992, the Drug Policy Research Center conducted a drug policy seminar game involving Florida public officials that anticipated this increase in cases as well as the need to provide drug abuse...
Rand, T., E-mail: email@example.com [General Hospital Hietzing, Department of Radiology (Austria); Uberoi, R. [John Radcliffe Hospital, Department of Radiology (United Kingdom)
Treatment of infrapopliteal arteries has developed to a standard technique during the past two decades. With the introduction of innovative devices, a variety of techniques has been created and is still under investigation. Treatment options range from plain balloon angioplasty (POBA), all sorts of stent applications, such as bare metal, balloon expanding, self-expanding, coated and drug-eluting stents, and bio-absorbable stents, to latest developments, such as drug-eluting balloons. Regarding the scientific background, several prospective, randomized studies with relevant numbers of patients have been (or will be) published that are Level I evidence. In contrast to older studies, which primarily were based mostly on numeric parameters, such as diameters or residual stenoses, more recent study concepts focus increasingly on clinical features, such as amputation rate improvement or changes of clinical stages and quality of life standards. Although it is still not decided, which of the individual techniques might be the best one, we can definitely conclude that whatever treatment of infrapopliteal arteries will be used it is of substantial benefit for the patient. Therefore, the goal of this review is to give an overview about the current developments and techniques for the treatment of infrapopliteal arteries, to present clinical and technical results, to weigh individual techniques, and to discuss the recent developments.
Rand, T.; Uberoi, R.
Treatment of infrapopliteal arteries has developed to a standard technique during the past two decades. With the introduction of innovative devices, a variety of techniques has been created and is still under investigation. Treatment options range from plain balloon angioplasty (POBA), all sorts of stent applications, such as bare metal, balloon expanding, self-expanding, coated and drug-eluting stents, and bio-absorbable stents, to latest developments, such as drug-eluting balloons. Regarding the scientific background, several prospective, randomized studies with relevant numbers of patients have been (or will be) published that are Level I evidence. In contrast to older studies, which primarily were based mostly on numeric parameters, such as diameters or residual stenoses, more recent study concepts focus increasingly on clinical features, such as amputation rate improvement or changes of clinical stages and quality of life standards. Although it is still not decided, which of the individual techniques might be the best one, we can definitely conclude that whatever treatment of infrapopliteal arteries will be used it is of substantial benefit for the patient. Therefore, the goal of this review is to give an overview about the current developments and techniques for the treatment of infrapopliteal arteries, to present clinical and technical results, to weigh individual techniques, and to discuss the recent developments.
Full Text Available Strongyloidiasis is a parasitic neglected disease caused by the nematode Strongyloides stercoralis affecting 30 to 100 million people worldwide. Complications, strongly associated with alcoholism, organ transplants, and HTLV-1 virus, often arise due to late diagnosis, frequently leading to patient death. Lack of preemptive diagnosis is not the only difficulty when dealing with this parasite, since there are no gold standard diagnostic techniques, and the ones used have problems associated with sensitivity, resulting in false negatives. Treatment is also an issue as ivermectin and benzimidazoles administration leads to inconsistent cure rates and several side effects. Researching new anti-Strongyloides drugs is a difficult task since S. stercoralis does not develop until the adult stages in Mus musculus (with the exception of SCID mice, the main experimental host model. Fortunately, alternative parasite models can be used, namely, Strongyloides ratti and S. venezuelensis. However, even with these models, there are other complications in finding new drugs, which are associated with specific in vitro assay protocol steps, such as larvae decontamination. In this review, we highlight the challenges associated with new drug search, the compounds tested, and a list of published in vitro assay methodologies. We also point out advances being made in strongyloidiasis diagnosis so far.
Cooper, Gail; Moeller, Manfred; Kronstrand, Robert
At the annual meeting of the Society of Hair Testing in Vadstena, Sweden in 2006, a committee was appointed to address the issue of guidelines for hair testing and to assess the current status of accreditation amongst laboratories offering drug testing in hair. A short questionnaire was circulated amongst the membership and interested parties. Fifty-two responses were received from hair testing laboratories providing details on the amount and type of hair tests they offered and the status of accreditation within their facilities. Although the vast majority of laboratories follow current guidelines (83%), only nine laboratories were accredited to ISO/IEC 17025 for hair testing. A significant number of laboratories reporting that they were in the process of developing quality systems with a view to accrediting their methods within 2-3 years. This study provides an insight into the status of accreditation in hair testing laboratories and supports the need for guidelines to encourage best practice.
Styliński, Roman; Alzubedi, Adam; Rudzki, Sławomir
Intestinal stoma creation is one of the most common surgical procedures. The most common long-term complication following stoma creation is parastomal hernia, which according to some authors is practically unavoidable. Statistical differences of its occurrence are mainly due to patient observation time and evaluation criteria. Consequently, primary prevention methods such as placement of prosthetic mesh and newly developed minimally invasive methods of stoma creation are used. It seems that in the light of evidence-based medicine, the best way to treat parastomal hernia is the one that the surgeon undertaking therapy is the most experienced in and is suited to the individuality of each patient, his condition and comorbidities. As a general rule, reinforcing the abdominal wall with a prosthetic mesh is the treatment of choice, with a low rate of complications and relapses over a long period of time. The current trend is to use lightweight, large pore meshes.
Full Text Available Toxic epidermal necrolysis (TEN is a clinical entity which has a 30 to 40 % mortality rate, with necrolysis affecting the entire epidermis. Antibiotics, nonsteroidal anti-inflammatory drugs and anticonvulsants are offender drugs in TEN etiology. A standard treatment protocol with proven efficacy is still lacking. In this study, current treatment practice and our treatment strategy for TEN is discussed and eight patients treated in our clinic between the years 2001 and 2008 are reviewed.
Tomek, Seven E; Lacrosse, Amber L; Nemirovsky, Natali E; Olive, M Foster
Glutamate plays a pivotal role in drug addiction, and the N-methyl-D-aspartate (NMDA) glutamate receptor subtype serves as a molecular target for several drugs of abuse. In this review, we will provide an overview of NMDA receptor structure and function, followed by a review of the mechanism of action, clinical efficacy, and side effect profile of NMDA receptor ligands that are currently in use or being explored for the treatment of drug addiction. These ligands include the NMDA receptor modulators memantine and acamprosate, as well as the partial NMDA agonist D-cycloserine. Data collected to date suggest that direct NMDA receptor modulators have relatively limited efficacy in the treatment of drug addiction, and that partial agonism of NMDA receptors may have some efficacy with regards to extinction learning during cue exposure therapy. However, the lack of consistency in results to date clearly indicates that additional studies are needed, as are studies examining novel ligands with indirect mechanisms for altering NMDA receptor function.
M. Foster Olive
Full Text Available Glutamate plays a pivotal role in drug addiction, and the N-methyl-D-aspartate (NMDA glutamate receptor subtype serves as a molecular target for several drugs of abuse. In this review, we will provide an overview of NMDA receptor structure and function, followed by a review of the mechanism of action, clinical efficacy, and side effect profile of NMDA receptor ligands that are currently in use or being explored for the treatment of drug addiction. These ligands include the NMDA receptor modulators memantine and acamprosate, as well as the partial NMDA agonist D-cycloserine. Data collected to date suggest that direct NMDA receptor modulators have relatively limited efficacy in the treatment of drug addiction, and that partial agonism of NMDA receptors may have some efficacy with regards to extinction learning during cue exposure therapy. However, the lack of consistency in results to date clearly indicates that additional studies are needed, as are studies examining novel ligands with indirect mechanisms for altering NMDA receptor function.
Islam, Manirul; Hashizume, Masahiro; Yamamoto, Taro; Alam, Faruq; Rabbani, Golam
Drug use is an alarming issue in Bangladesh. Most drug users return to drugs after treatment, in what becomes a vicious cycle of treatment and relapse. This study explored why they return and what pathways they follow. We carried out 5 key informant interviews, 10 in-depth interviews, 2 focus group discussions, 3 case studies, 8 observations, and…
Gschwind, Markus; Seeck, Margitta
Neuromodulation (NM) is a complementary therapy for patients with drug-resistant epilepsy. Vagal nerve stimulation and deep brain stimulation of the anterior thalamus are established techniques and have shown their efficacy in lowering seizure frequency, but they are invasive and rarely render patients seizure-free. Non-invasive NM techniques are therefore increasingly investigated in a clinical context. Areas covered: Current knowledge about transcranial direct-current stimulation (tDCS) and other non-invasive NM in patients with epilepsy, based on the available animal and clinical studies from PubMed search. Expert commentary: tDCS modulates neuronal membrane potentials, and consequently alters cortical excitability. Cathodal stimulation leads to cortical inhibition, which is of particular importance in epilepsy treatment. The antiepileptic efficacy is promising but still lacks systematic studies. The beneficial effect, seen in ~20%, outlasts the duration of stimulation, indicating neuronal plasticity and is therefore of great interest to obtain long-term effects.
Rico-Villademoros, F; Calandre, E P; Slim, M
The treatment of fibromyalgia requires pharmacological and nonpharmacological therapies. The pharmacological treatment of fibromyalgia is limited to a few drugs that have been demonstrated to be moderately effective in some but not all dimensions of the disease. Therefore, the search for new drugs to treat this condition is warranted. Atypical antipsychotics offered an attractive alternative because they had been shown to be active against several key symptoms of fibromyalgia. The results of open-label studies, however, appear to indicate that atypical antipsychotics are poorly tolerated in patients with fibromyalgia, and only quetiapine XR has been studied in randomized controlled trials. Quetiapine XR has demonstrated effectiveness in treating comorbid major depression, anxiety and sleep disturbance. However, in two randomized controlled trials, quetiapine XR was not differentiated from placebo and failed to demonstrate noninferiority to amitriptyline in terms of improving overall symptomatology. The effect of quetiapine XR on pain and its usefulness as part of a combination pharmacological regimen should be further evaluated. Overall, the use of quetiapine (initiated at a low dose and slowly titrated) in fibromyalgia should be limited to patients with comorbid major depression or patients who are currently receiving other treatments and have unresolved and disabling depressive and/or anxiety symptoms. Copyright 2014 Prous Science, S.A.U. or its licensors. All rights reserved.
The Cape Town Drug Counselling Centre is an outpatient drug treatment ... Management of clients, which includes psychotherapy with an emphasis on ... medical intervention, is described, and proposed areas for further research are outlined.
Mincarone, Pierpaolo; Leo, Carlo Giacomo; Sabina, Saverio; Sarriá-Santamera, Antonio; Taruscio, Domenica; Serrano-Aguilar, Pedro Guillermo; Kanavos, Panos
The pricing and reimbursement policies for pharmaceuticals are relevant to balance timely and equitable access for all patients, financial sustainability, and reward for valuable innovation. The proliferation of high-cost specialty medicines is particularly true in rare diseases (RDs) where the pricing mechanism is characterised by a lack of transparency. This work provides an overall picture of current strategies for the definition of the reimbursed prices of orphan drugs (ODs) and highlights some potential improvements. Current strategies and suggestions are presented along 4 dimensions: (1) comprehensive value assessment, (2) early dialogs among relevant stakeholders, (3) innovative reimbursement approaches, and (4) societal participation in producing ODs. Comprehensive value assessment could be achieved by clarifying the approach of distributive justice to adopt, ensuring a representative participation of stakeholders, and with a broad consideration of value-bearing factors. With respect to early dialogs, cross-border cooperation can be determinant to companies and agencies. The cost-benefit ratio of early dialogs needs to be demonstrated and the "regulatory capture" effect should be monitored. Innovative reimbursement approaches were developed to balance the need for evidence-based decisions with the timely access to innovative drugs. The societal participation in producing ODs needs to be recognised in a collaborating framework where adaptive agreements can be developed with mutual satisfaction. Such agreements could also impact on coverage and reimbursement decisions as additional elements for the determination of a comprehensive societal value of ODs. Further research is needed to investigate the highlighted open challenges so that RDs will not remain, in practical terms, orphan diseases. © 2017 S. Karger AG, Basel.
Dan Carter carefully layered the sheets of tracing paper on the light box. On each sheet were renderings of the atomic components of an essential human protein, one whose structure had long been a mystery. With each layer Carter laid down, a never-before-seen image became clearer. Carter joined NASA s Marshall Space Flight Center in 1985 and began exploring processes of protein crystal growth in space. By bouncing intense X-rays off the crystals, researchers can determine the electron densities around the thousands of atoms forming the protein molecules, unveiling their atomic structures. Cultivating crystals of sufficient quality on Earth was problematic; the microgravity conditions of space were far more accommodating. At the time, only a few hundred protein structures had been mapped, and the methods were time consuming and tedious. Carter hoped his work would help reveal the structure of human serum albumin, a major protein in the human circulatory system responsible for ferrying numerous small molecules in the blood. More was at stake than scientific curiosity. Albumin has a high affinity for most of the world s pharmaceuticals, Carter explains, and its interaction with drugs can change their safety and efficacy. When a medication enters the bloodstream a cancer chemotherapy drug, for example a majority of it can bind with albumin, leaving only a small percentage active for treatment. How a drug interacts with albumin can influence considerations like the necessary effective dosage, playing a significant role in the design and application of therapeutic measures. In spite of numerous difficulties, including having no access to microgravity following the 1986 Space Shuttle Challenger disaster, the image Carter had hoped to see was finally clarifying. In 1988, his lab had acquired specialized X-ray and detection equipment a tipping point. Carter and his colleagues began to piece together albumin s portrait, the formation of its electron densities coalescing on
Faralli, Adele; Melander, Fredrik; Andresen, Thomas Lars
drug dosing” using light-‐polymerizable polymer hydrogels as carriers for free or nanoparticle-‐encapsulated drugs. The total dose is simply controlled by the volume of drug-‐loaded cross-‐ linked hydrogel defined by patterned light from a standard projector (Fig. 1). The concept enables simple...
Barra, Fabio; Lorusso, Domenica; Leone Roberti Maggiore, Umberto; Ditto, Antonino; Bogani, Giorgio; Raspagliesi, Francesco; Ferrero, Simone
Cervical cancer (CC) is currently the fourth most common malignant disease of women worldwide. Although the incidence and the mortality rates have been decreasing with screening detection and new treatment strategies, a significant number of metastatic or recurrent disease is still diagnosed. For those patients not amenable to curative treatments, such as surgery and radiation, palliative chemotherapy remains the standard of care. As chemotherapy regimens have limited activity, research is focalized on investigating novel pharmacologic strategies. Areas covered: This paper aims to give a complete and updated overview on investigated therapies for the treatment of CC. The authors review the results of clinical studies and highlight the ongoing trials. Expert opinion: Agents targeting various molecular pathways including epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), poly ADP-ribose polymerase (PARP), epigenetics and other biological mechanisms represent interesting investigational opportunities. Amongst such drugs, bevacizumab, an anti-VEGF monoclonal antibody, was the first targeted drug recently approved by the FDA for the treatment of patients with metastatic, recurrent, or persistent CC. Another interesting experimental approach is represented by immunotherapy, which is leading to promising results with to the development of therapeutic vaccines and immune checkpoints inhibitors.
Zumla, Alimuddin; Abubakar, Ibrahim; Raviglione, Mario; Hoelscher, Michael; Ditiu, Lucica; McHugh, Timothy D; Squire, S Bertel; Cox, Helen; Ford, Nathan; McNerney, Ruth; Marais, Ben; Grobusch, Martin; Lawn, Stephen D; Migliori, Giovanni-Battista; Mwaba, Peter; O'Grady, Justin; Pletschette, Michel; Ramsay, Andrew; Chakaya, Jeremiah; Schito, Marco; Swaminathan, Soumya; Memish, Ziad; Maeurer, Markus; Atun, Rifat
Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. Following the declaration and the promotion in 1995 of directly observed treatment short course (DOTS), a cost-effective strategy to contain the tuberculosis epidemic, nearly 7 million lives have been saved compared with the pre-DOTS era, high cure rates have been achieved in most countries worldwide, and the global incidence of tuberculosis has been in a slow decline since the early 2000s. However, the emergence and spread of multidrug-resistant (MDR) tuberculosis, extensively drug-resistant (XDR) tuberculosis, and more recently, totally drug-resistant tuberculosis pose a threat to global tuberculosis control. Multidrug-resistant tuberculosis is a man-made problem. Laboratory facilities for drug susceptibility testing are inadequate in most tuberculosis-endemic countries, especially in Africa; thus diagnosis is missed, routine surveillance is not implemented, and the actual numbers of global drug-resistant tuberculosis cases have yet to be estimated. This exposes an ominous situation and reveals an urgent need for commitment by national programs to health system improvement because the response to MDR tuberculosis requires strong health services in general. Multidrug-resistant tuberculosis and XDR tuberculosis greatly complicate patient management within resource-poor national tuberculosis programs, reducing treatment efficacy and increasing the cost of treatment to the extent that it could bankrupt healthcare financing in tuberculosis-endemic areas. Why, despite nearly 20 years of WHO-promoted activity and >12 years of MDR tuberculosis-specific activity, has the country response to the drug-resistant tuberculosis epidemic been so ineffectual? The current dilemmas, unanswered questions, operational issues, challenges, and priority needs for global drug resistance screening and surveillance, improved treatment regimens, and management of outcomes and prevention of DR
Chole, Revant H; Gondivkar, Shailesh M; Gadbail, Amol R; Balsaraf, Swati; Chaudhary, Sudesh; Dhore, Snehal V; Ghonmode, Sumeet; Balwani, Satish; Mankar, Mugdha; Tiwari, Manish; Parikh, Rima V
This study undertook a review of the literature on drug treatment of oral submucous fibrosis. An electronic search was carried out for articles published between January 1960 to November 2011. Studies with high level of evidence were included. The levels of evidence of the articles were classified after the guidelines of the Oxford Centre for Evidence-Based Medicine. The main outcome measures used were improvement in oral ulceration, burning sensation, blanching and trismus. Only 13 publications showed a high level of evidence (3 randomized controlled trials and 10 clinical trials/controlled clinical trials), with a total of 1157 patients. Drugs like steroids, hyaluronidase, human placenta extracts, chymotrypsin and collagenase, pentoxifylline, nylidrin hydrochloride, iron and multivitamin supplements including lycopene, have been used. Only systemic agents were associated with few adverse effects like gastritis, gastric irritation and peripheral flushing with pentoxifylline, and flushingly warm skin with nylidrin hydrochloride; all other side-effects were mild and mainly local. Few studies with high levels of evidence were found. The drug treatment that is currently available for oral submucous fibrosis is clearly inadequate. There is a need for high-quality randomized controlled trials with carefully selected and standardized outcome measures. Copyright © 2011 Elsevier Ltd. All rights reserved.
Pottegård, Anton; Bjerregaard, B. K.; Kortegaard, L. S.
Knowledge of patterns of treatment discontinuation in attention-deficit/hyperactivity disorder (ADHD) drug treatment is of importance, for both the clinical practice and the study of long-term treatment outcomes. The purpose of this study was to describe early discontinuation of ADHD drug treatme...
..., holding, or distribution of PET drugs intended for human use. Current good manufacturing practice is... 21 Food and Drugs 4 2010-04-01 2010-04-01 false What is current good manufacturing practice for... HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR POSITRON EMISSION...
The thesis deals with the spirituality of a drug addiction therapy. The first chapter classifies drugs and characterizes drug addictions and their therapies. To clear up the context and point of view, the second chapter explains the meaning of spirituality in relation to its development. First, it intorduces the ancient spirituality, based on heatheninsmas, a meaning of Sanctity in relation to our ethnic origin. Further on, it pictures the Christian spirituality with its practical aspects. Ne...
Pescosolido, Nicola; Stefanucci, Alessio; Buomprisco, Giuseppe; Fazio, Stefano
Amblyopia is a unilateral or bilateral reduction of visual acuity secondary to abnormal visual experience during early childhood. It is one of the most common causes of vision loss and monocular blindness and is commonly associated with strabismus, anisometropia, and visual deprivation (in particular congenital cataract and ptosis). It is clinically defined as a two-line difference of best-corrected visual acuity between the eyes. The purpose of this study was to understand the neural mechanisms of amblyopia and summarize the current therapeutic strategies. In particular, the authors focused on the concept of brain plasticity and its implication for new treatment strategies for children and adults with amblyopia. Copyright 2014, SLACK Incorporated.
Hulvershorn, Leslie A; Schroeder, Kristen M; Wink, Logan K; Erickson, Craig A; McDougle, Christopher J
This pilot study compared the pharmacologic treatment history and clinical outcomes observed in pediatric outpatients with psychiatric disorders exposed to drugs of abuse in utero to those of an age-matched, sex-matched and psychiatric disorder-matched, non-drug-exposed group. In this matched cohort study, medical records of children treated at an academic, child and adolescent psychiatry outpatient clinic were reviewed. Children with caregiver-reported history of prenatal drug exposure were compared with a non-drug-exposed control group being cared for by the same providers. Patients were rated with the Clinical Global Impressions-Severity scale (CGI-S) throughout treatment. The changes in pre-treatment and post-treatment CGI-S scores and the total number of medication trials were determined between groups. The drug-exposed group (n = 30) had a higher total number of lifetime medication trials compared with the non-drug-exposed group (n = 28) and were taking significantly more total medications, at their final assessment. Unlike the non-drug-exposed group, the drug-exposed group demonstrated a lack of clinical improvement. These results suggest that in utero drug-exposed children may be more treatment-refractory to or experience greater side effects from the pharmacologic treatment of psychiatric disorders than controls, although we cannot determine if early environment or drugs exposure drives these findings. Copyright © 2015 John Wiley & Sons, Ltd.
Maria Isabela Sarbu
Full Text Available Erectile dysfunction (ED is the inability to achieve and maintain an erection sufficient for satisfactory sexual intercourse. It is the most frequent sexual dysfunction in elderly men and its prevalence increases with age. Ever since ED was recognized as a real health problem, several treatment options became available and some of them proved to be very efficient. PDE5 inhibitors are the mainstay treatment of ED. However, other treatment options such as intracorporal injections, surgery, vacuum devices and prosthesis are also available for patients who are unresponsive to PDE5 inhibitors. Since none of the treatment options available so far has proven ideal, research in the field of sexual medicine continues. The aim of this paper is to review the most advances in the treatment of ED.
Naidoo, Anushka; Naidoo, Kogieleum; McIlleron, Helen; Essack, Sabiha; Padayatchi, Nesri
Moxifloxacin, an 8-methoxy quinolone, is an important drug in the treatment of multidrug-resistant tuberculosis and is being investigated in novel drug regimens with pretomanid, bedaquiline, and pyrazinamide, or rifapentine, for the treatment of drug-susceptible tuberculosis. Early results of these studies are promising. Although current evidence does not support the use of moxifloxacin in treatment-shortening regimens for drug-susceptible tuberculosis, it may be recommended in patients unable to tolerate standard first-line drug regimens or for isoniazid monoresistance. Evidence suggests that the standard 400-mg dose of moxifloxacin used in the treatment of tuberculosis may be suboptimal in some patients, leading to worse tuberculosis treatment outcomes and emergence of drug resistance. Furthermore, a drug interaction with the rifamycins results in up to 31% reduced plasma concentrations of moxifloxacin when these are combined for treatment of drug-susceptible tuberculosis, although the clinical relevance of this interaction is unclear. Moxifloxacin exhibits extensive interindividual pharmacokinetic variability. Higher doses of moxifloxacin may be needed to achieve drug exposures required for improved clinical outcomes. Further study is, however, needed to determine the safety of proposed higher doses and clinically validated targets for drug exposure to moxifloxacin associated with improved tuberculosis treatment outcomes. We discuss in this review the evidence for the use of moxifloxacin in drug-susceptible tuberculosis and explore the role of moxifloxacin pharmacokinetics, pharmacodynamics, and drug interactions with rifamycins, on tuberculosis treatment outcomes when used in first-line tuberculosis drug regimens. © 2017, The American College of Clinical Pharmacology.
Wang Chunmei; Wang Xuemei
Hyperthyroidism is an autoimmune diseasein which excessive amounts of thyroid hormones circulate in the blood. The treatments for hyperthyroidism mainly include antithyroid drugs, 131 I treatment, and surgery. 131 I had been verified as an effective, safe, simple method to treat adult and children hyperthyroidism. Current research trends of 131 I treatment mainly are problems of 131 I treatment of hyperthyroidism and its long-term security. (authors)
Schwarz, Peter; Jørgensen, Niklas Rye; Abrahamsen, Bo
supplementation. Several new medications for the treatment of postmenopausal osteoporosis are in the pipeline. AREAS COVERED: The authors present the most recent studies on new and current antiresorptive as well as anabolic drugs. Specifically, the authors present the current knowledge on drugs directed against...... cathepsin K and sclerostin as well as the new pathways of interest from preclinical studies. EXPERT OPINION: New scientific results have identified novel signaling pathways as potential targets for future development of anti-osteoporotic drugs. The treatments close to marketing at the moment are odanacatib...
Full Text Available Introduction. Cough is one of the most common symptoms in the practice of doctors of various specialties, including pediatricians. Cough treatment should be started with the identification of its cause and correct diagnosis. Most often, cough in children is due to the increased viscosity of bronchial secretions, i.e. violation of sputum transport in the bronchial tree, and insufficient activity of ciliated epithelium. The main objective of the treatment of productive cough is dilution of sputum, bronchial secretion and excretion, thus necessitating the administration of mucolytics. Currently, one of the most famous mucolytics is acetylcysteine, cysteine amino acid product, such as ACC®. However, today the question of ACC® (acetylcysteine application in infants and young children is still debatable. This article presents a study whose objective was to evaluate the therapeutic efficacy and tolerability of ACC® (20 mg/ml solution in the treatment of bronchopulmonary diseases in children aged 2 to 6 years. Materials and methods. The study involved 60 children with acute tracheitis, simple bronchitis, acute obstructive bronchitis, recurrent bronchitis in the acute phase, community-acquired pneumonia, asthma exacerbation, cystic fibrosis. Patients of the main groups (n = 40 received ACC® (20 mg/ml solution at the age-specific dosage 3 times a day in combined treatment. Therapy of patients in the control group (n = 20 was conducted without ACC®. Results. During follow-up, patients who received ACC® had significant positive changes in the nature of cough, sputum viscosity and its amount as opposed to a comparison group of patients. Complete disappearance of cough was achieved on day 5–8 from the beginning of treatment, while in the control group patients, this time was longer. The evaluation of the effectiveness of the study drug showed that very good efficacy was achieved in 75 % of patients and good — in 20 %, and among patients who
The studies in this thesis together show different ways of studying human pharmacology, give an impression of the current drug development in schizophrenia, and provide examples how human pharmacology can be applied in an early stage of drug development in healthy volunteers. The investigated
Conclusions: Prevalence of suicidal ideation/plans was high among illicit drug users recruited from healthcare facilities. Besides psychological variables, participation in illegal market activities and crime ought to be considered in drug users’ suicidal prevention. Suicide risk needs to be evaluated in drug treatment facilities and psychological status and context contemplated.
Rizzo, Renata; Gulisano, Mariangela; Calì, Paola V; Curatolo, Paolo
Attention Deficit Hyperactivity Disorder (ADHD) is the most common co-morbid condition encountered in people with tics and Tourette Syndrome (TS). The co-occurrence of TS and ADHD is associated with a higher psychopathological, social and academic impairment and the management may represent a challenge for the clinicians. To review recent advances in management of patients with tic, Tourette Syndrome and comorbid Attention Deficit Hyperactivity Disorder. We searched peer reviewed and original medical publications (PUBMED 1990-2012) and included randomized, double-blind, controlled trials related to pharmacological treatment for tic and TS used in children and adolescents with comorbid ADHD. "Tourette Syndrome" or "Tic" and "ADHD", were cross referenced with the words "pharmacological treatment", "α-agonist", "psychostimulants", "selective norepinephrine reuptake inhibitor", "antipsychotics". Three classes of drugs are currently used in the treatment of TS and comorbid ADHD: α-agonists (clonidine and guanfacine), stimulants (amphetamine enantiomers, methylphenidate enantiomers or slow release preparation), and selective norepinephrine reuptake inhibitor (atomoxetine). It has been recently suggested that in a few selected cases partial dopamine agonists (aripiprazole) could be useful. Level A of evidence supported the use of noradrenergic agents (clonidine). Reuptake inhibitors (atomoxetine) and stimulants (methylphenidate) could be, also used for the treatment of TS and comorbid ADHD. Taking into account the risk-benefit profile, clonidine could be used as the first line treatment. However only few studies meet rigorous quality criteria in terms of study design and methodology; most trials have low statistical power due to small sample size or short duration. Treatment should be "symptom targeted" and personalized for each patient. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Gómez Cabrera, Erasmo Pablo
The document deals with the cancer situation in Cuba; the factors that produce and causes destruction of bone metastases. It also describes osteoblastic and osteolytic lesions; and details the different treatments for bone metastases
Among communicable diseases, tuberculosis (TB) is the second leading ... There may be need to modify the treatment modalities especially with the ... liver disease, renal failure or even in coexistence with HIV/AIDS or the drug resistant state.
Friedmann, P D; Lemon, S C; Stein, M D
To determine whether certain types of transportation assistance improve outpatient treatment retention beyond thresholds shown to have therapeutic benefits, we analyzed data from 1,144 clients in 22 outpatient methadone maintenance (OMM) programs and 2,031 clients in 22 outpatient drug-free (ODF) programs in the Drug Abuse Treatment Outcomes Study (DATOS), a national, 12-month, longitudinal study of drug abuse treatment programs. Directors' surveys provided information about provision of car, van, or contracted transportation services or individual vouchers/payment for public transportation. Chart-abstracted treatment retention was dichotomized at 365 days for OMM and 90 days for ODF. Separate multivariate hierarchical linear models revealed that provision of car, van, or contracted transportation services improved treatment retention beyond these thresholds for both OMM and ODF, but individual vouchers or payment for public transportation did not. Future research should validate whether car, van, or contracted transportation services improve retention and other treatment outcomes in outpatient drug abuse treatment.
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
Quan Q Dinh
Full Text Available Quan Q Dinh, Rodney SinclairDepartment of Dermatology, St Vincent’s Hospital, Fitzroy, Victoria, AustraliaAbstract: Fewer than 45% of women go through life with a full head of hair. Female pattern hair loss is the commonest cause of hair loss in women and prevalence increases with advancing age. Affected women may experience psychological distress and impaired social functioning. In most cases the diagnosis can be made clinically and the condition treated medically. While many women using oral antiandrogens and topical minoxidil will regrow some hair, early diagnosis and initiation of treatment is desirable as these treatments are more effective at arresting progression of hair loss than stimulating regrowth. Adjunctive nonpharmacological treatment modalities such as counseling, cosmetic camouflage and hair transplantation are important measures for some patients. The histology of female pattern hair loss is identical to that of male androgenetic alopecia. While the clinical pattern of the hair loss differs between men, the response to oral antiandrogens suggests that female pattern hair loss is an androgen dependant condition, at least in the majority of cases. Female pattern hair loss is a chronic progressive condition. All treatments need to be continued to maintain the effect. An initial therapeutic response often takes 12 or even 24 months. Given this delay, monitoring for treatment effect through clinical photography or standardized clinical severity scales is helpful.Keywords: female pattern hair loss, androgenetic alopecia
Jamroziak, Krzysztof; Puła, Bartosz; Walewski, Jan
A number of new treatment options have recently emerged for chronic lymphocytic leukemia (CLL) patients, including the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, phosphatidylinositol-3-kinase (PI3K) delta isoform inhibitor idelalisib combined with rituximab, the Bcl-2 antagonist venetoclax, and the new anti-CD20 antibodies obinutuzumab and ofatumumab. Most of these agents are already included into treatment algorithms defined by international practice guidelines, but more clinical investigations are needed to answer still remaining questions. Ibrutinib was proven as a primary choice for patients with the TP53 gene deletion/mutation, who otherwise have no active treatment available. Idelalisib with rituximab is also an active therapy, but due to increased risk of serious infections, its use in first-line treatment is limited to patients for whom ibrutinib is not an option. A new indication for ibrutinib was recently approved for older patients with comorbidities, as an alternative to the already existing indication for chlorambucil with obinutuzumab. The use of kinase inhibitors is already well established in recurrent/refractory disease. Immunochemotherapy with fludarabine, cyclophosphamide, rituximab (FCR) remains a major first-line option for many CLL patients without the TP53 gene deletion/mutation, and who have no significant comorbidities or history of infections, and is particularly effective in patients with favorable features including mutated IGHV status. There are a number of issues regarding novel therapies for CLL that need further investigation such as optimum duration of treatment with kinase inhibitors, appropriate sequencing of novel agents, mechanisms of resistance to inhibitors and response to class switching after treatment failure, along with the potential role of combinations of targeted agents.
Sykora, P.; Svecova, L.
Epilepsy is the most prevalent chronic brain disease manifesting with epileptic seizures. Epilepsy itself is not one nosological entity, it rather includes several diseases with various etiology, clinics, course and therapy. Antiepileptic therapy aims seizure freedom without affecting psychical and physical functions. The therapy is in first line pharmacological. The choice of antiepileptic drug depends not only on the seizure phenomenology, but also on the respective type of epilepsy syndrome. Most patients achieve seizure freedom or at least significant seizure frequency reduction. In 20-30% of the patients is the pharmacotherapy ineffective. In these cases of refractory epilepsy therapeutical options include epilepsy surgery, vagal stimulation or ketogenic diet. Despite recent advances in the diagnostics and therapy, epilepsy remains a serious medical and social issue. (author)
Among the various routes of drug delivery, the vaginal route offers many advantages due to its large permeation area, rich vascularization, avoidance of first pass metabolism and relatively low enzymatic activity. Several studies have shown that the vaginal cavity is an effective route for drug administration intended mainly ...
Kerkhof, P.C.M. van de; Kleinpenning, M.M.; Jong, E.M.G.J. de; Gerritsen, M.J.P.; Dooren-Greebe, R.J. van; Alkemade, J.A.C.
Acne is a frequent skin disease with abnormalities in the process of keratinization, sebaceous gland functioning and inflammation. In this review, our understanding of the pathogenesis of acne has been updated. An overview of efficacy and side effects of available anti-acne treatments is presented.
Norvilitis, Jill M., Ed.
The treatment of Attention Deficit Hyperactivity Disorder is a matter of ongoing research and debate, with considerable data supporting both psychopharmacological and behavioral approaches. Researchers continue to search for new interventions to be used in conjunction with or in place of the more traditional approaches. These interventions run the…
Eduardo Chaves Cruz
Full Text Available Three short-term interventions have been corroborated for the treatment of ADHD (Attention Deficit Hyperactivity Disorder: psychotherapeutic (behavioural, psychopharmacological, and the combining of both interventions. This article reviews clinical questions, limitations and efficacy of these interventions. Behavioural interventions in the form of Parental Behavioural Training and the Management of Behavioural Contingencies in the Classroom seem to be particularly efficacious.
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.
McCusker, J; Willis, G; McDonald, M; Lewis, B F; Sereti, S M; Feldman, Z T
The outcomes of counseling and testing programs related to human immunodeficiency virus (HIV) infection and risk of infection among injection drug users (IDUs) are not well known or understood. A counseling and testing outcome of potential public health importance is attaining admission to drug abuse treatment by those IDUs who are either infected or who are at high risk of becoming infected. The authors investigated factors related to admission to drug abuse treatment among 519 IDUs who received HIV counseling and testing from September 1987 through December 1990 at a men's prison and at community-based testing sites in Worcester, MA. By June 1991, 123 of the 519 IDUs (24 percent) had been admitted to treatment. Variables associated with their admission included a long history of drug injection, frequent recent drug injection, cleaning injection equipment using bleach, prior drug treatment, and a positive HIV test result. Logistic regression analyses, controlling for effects of recruitment site, year, sex, and area of residence, generally confirmed the associations. IDUs in the study population who were HIV-infected sought treatment or were admitted to treatment more frequently than those who were not infected. The results indicate that access to drug abuse treatment should be facilitated for high-risk IDUs and for those who have begun to inject drugs recently.
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....
Michel, Morgane; Toumi, Mondher
Orphan drugs target small populations of patients. In order to make the field more attractive to pharmaceutical companies and encourage R&D in rare diseases, incentives were put forward by the EU, which are discussed in this article. Because they often are the only available option to treat a disease, some orphan drugs are considered to have high value and as such benefit from high prices on national markets. This has made orphan drugs an attractive market for pharmaceutical companies, with approximately 40 approved orphan drugs generating over $200 million each in yearly sales. The resulting burden this puts on national health insurances may lead to a change in regulation and will certainly lead to new national pricing and reimbursement strategies. They will need to be coherent, fair, effective and sustainable so as to be predictable for companies. Reflection on the subject needs to be initiated.
Ear disease, such as otitis externa, resulting in aggressive head shaking or ear scratching, is the most common cause of the development of aural hematomas in dogs and cats. An underlying immunologic cause has also been proposed to explain cartilage and blood vessel fragility. Numerous options exist for management of aural hematomas, from medical management alone with corticosteroids, to simple hematoma centesis, to surgical intervention. Because this condition is usually secondary to another disease process, regardless of mode of treatment, likelihood of recurrence is low if the underlying condition is managed properly. Copyright © 2016 Elsevier Inc. All rights reserved.
Sovani, Sujata; Grogan, Shawn P
Osteoarthritis (OA) is a disease of the joint, and age is the major risk factor for its development. Clinical manifestation of OA includes joint pain, stiffness, and loss of mobility. Currently, no pharmacological treatments are available to treat this specific joint disease; only symptom-modifying drugs are available. Improvement in imaging technology, identification of biomarkers, and increased understanding of the molecular basis of OA will aid in detecting the early stages of disease. Yet the development of interventional strategies remains elusive and will be critical for effective prevention of OA-associated joint destruction. The potential of cell-based therapies may be applicable in improving joint function in mild to more advanced cases of OA. Ongoing studies to understand the basis of this disease will eventually lead to prevention and treatment strategies and will also be a key in reducing the social and economic burden of this disease. Nurses are advised to provide an integrative approach of disease assessment and management in OA patients' care with a focus on education and implementation. Knowledge and understanding of OA and how this affects the individual patient form the basis for such an integrative approach to all-round patient care and disease management.
Sep 14, 1974 ... relieve the physician, at his discretion, in the medication management of patients. S. Afr. Med. J., 48, 1920 (1974). The practice of medicine has both benefited and suffered from the vast upsurge of drug discovery in the past 30 to 40 years. Thus, in accepting the benefits, there has come the realisation of ...
Nicosia, Nancy; Macdonald, John M; Arkes, Jeremy
We investigated the extent to which racial/ethnic disparities in prison and diversion to drug treatment were explained by current arrest and criminal history characteristics among drug-involved offenders, and whether those disparities decreased after California's Proposition 36, which mandated first- and second-time nonviolent drug offenders drug treatment instead of prison. We analyzed administrative data on approximately 170,000 drug-involved arrests in California between 1995 and 2005. We examined odds ratios from logistic regressions for prison and diversion across racial/ethnic groups before and after Proposition 36. We found significant disparities in prison and diversion for Blacks and Hispanics relative to Whites. These disparities decreased after controlling for current arrest and criminal history characteristics for Blacks. Proposition 36 was also associated with a reduction in disparities, but more so for Hispanics than Blacks. Disparities in prison and diversion to drug treatment among drug-involved offenders affect hundreds of thousands of citizens and might reinforce imbalances in criminal justice and health outcomes. Our study indicated that standardized criminal justice policies that improved access to drug treatment might contribute to alleviating some share of these disparities.
González García, A; Moreno Cobo, M Á; Patier de la Peña, J L
Castleman's disease is not just a single disease but rather an uncommon, heterogeneous group of nonclonal lymphoproliferative disorders, which have a broad spectrum of clinical expression. Three histological types have been reported, along with several clinical forms according to clinical presentation, histological substrate and associated diseases. Interleukin-6, its receptor polymorphisms, the human immunodeficiency virus and the human herpes virus 8 are involved in the etiopathogenesis of Castleman's disease. The study of this disease has shed light on a syndrome whose incidence is unknown. Despite recent significant advances in our understanding of this disease and the increasing therapeutic experience with rituximab, tocilizumab and siltuximab, there are still difficult questions concerning its aetiology, prognosis and optimal treatment. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.
Carfagna, Fabio; Del Vecchio, Lucia; Pontoriero, Giuseppe; Locatelli, Francesco
Hyperphosphatemia is common in late stages of chronic kidney disease and is often associated with elevated parathormone levels, abnormal bone mineralization, extra-osseous calcification, and increased risk of cardiovascular events and death. Several classes of oral phosphate binders are available to help control plasma phosphorus levels. Although effective at lowering serum phosphorus, they all have safety, tolerability, and compliance issues that need to be considered when selecting which one to use. Areas covered: This paper reviews the most established treatment options for hyperphosphatemia, in patients with chronic kidney disease, focusing on the new inhibitors of active phosphate absorption. Expert opinion: The prevention and the treatment of hyperphosphatemia is today far to be satisfactory. Nonetheless, an extending range of phosphate binders are now available. Aluminum has potentially serious toxic risks. Calcium-based binders are very effective but can lead to hypercalcemia and/or positive calcium balance and progression of cardiovascular calcification. No long-term data are available for the new calcium acetate/magnesium combination product. Lanthanum is an effective phosphate binder, and long-term effects of tissue deposition seem clinically irrelevant. Sevelamer, appear to have profiles that would lead to pleiotropic effects and reduced progression of vascular calcification, and the main adverse events seen with these agents are gastrointestinal. Iron has a powerful capability of binding phosphate, thus numerous preparations are available, both with and without significant systemic absorption of the iron component. The inhibitors of active intestinal phosphate transport, with their very selective mechanism of action and low pill burden seem the most interesting approach; however, do not seem at present to be effective alone, in reducing serum phosphorus levels.
Mehmet Mustafa Kılıçkaya
Full Text Available Halitosis or oral malodor is not a diagnosis, but is symptom. Halitosis, that we frequently encounter in ear, nose and throat practice can be the harbinger of some serious underlying disease. Therefore, diagnosis and to find the cause of the halitosis are important. Also halitosis treatment is necessary due to the social and psychological effects. Breath contains hundreds of volatile organic compounds that are by-products of our metabolism. Certain diseases such as nasopharynx cancer, larynx cancer ve lung cancer alter the mix of gases. Thus, the analysis of exhaled air has gained importance. New technologies lead to the development of new devices. And with these called electronic noses the analysis of exhaled air has becomes an important non-invasive diagnostic method. In the literature, halitosis and bad breath which is used as synonymus with oral malodor is the emission of unpleasant odor from mouth and nasal passage. It occurs in 25% of the population, approximately and it has a significant social and economic impact. Halitosis is classified as true halitosis (physiologic halitosis and pathologic halitosis, pseudohalitosis and halitophobia. The most common cause is intra-oral diseases. Among all these factors, the most important etiologic factor are the coating tongue. Other ear, nose and throat diseases such as rhinitis and sinusitis are seen among the most common extraoral causes. Treponema denticola, Porphyromonas gingivalis, Tanneralla forsythia, Fusobacterium nucleatum, Prevotella intermedia, Prevotella nigrescens, Actinobacilli and Solobacterium moorei are the bacteria which are commonly isolated from patients with halitosis and they are volatile sulfur compounds (VSCs producing ones as well. The treatment of halitosis should be carried out according to the etiology. In the physiologic halitosis tooth brushing, use of dental floss, tongue cleaning and chlorhexidine, cetylpyridinium chloride and zinc containing antimicrobial mouthwashes
Washton, A M
This chapter describes the rationale, indications, design, and use of a structured outpatient treatment approach as an effective alternative to residential treatment for alcohol and drug dependencies. An increasing demand for outpatient treatment services is being created by a combination of clinical and economic factors, including the influx of employed drug abusers who do not need or desire residential care and mounting financial pressures to contain health care costs. To be effective as a primary treatment modality, outpatient programs must be highly structured and intensive and able to deal with the full spectrum of alcohol and drug addictions. Perpetuating the historical separation between alcoholism and drug abuse treatment programs is unnecessary and counterproductive, although certain modifications in treatment approaches are needed to accommodate the distinctive characteristics of particular classes of drugs and the people who use them. The "outpatient rehab," a treatment model that approximates the intensity of inpatient treatment on an outpatient basis, may help to maximize the clinical efficacy and cost-effectiveness of outpatient treatment as a viable alternative to residential care. Initial treatment results with this model are encouraging.
Full Text Available Hyperthyroidism is a common endocrine disease. Although thionamide antithyroid drugs are the cornerstone of hyperthyroidism treatment, some patients cannot tolerate this drug class because of its serious side effects including agranulocytosis, hepatotoxicity, and vasculitis. Therefore, nonthionamide antithyroid drugs (NTADs still have an important role in controlling hyperthyroidism in clinical practice. Furthermore, some situations such as thyroid storm or preoperative preparation require a rapid decrease in thyroid hormone by combination treatment with multiple classes of antithyroid drugs. NTADs include iodine-containing compounds, lithium carbonate, perchlorate, glucocorticoid, and cholestyramine. In this narrative review, we summarize the mechanisms of action, indications, dosages, and side effects of currently used NTADs for the treatment of hyperthyroidism. In addition, we also describe the state-of-the-art in future drugs under development including rituximab, small-molecule ligands (SMLs, and monoclonal antibodies with a thyroid-stimulating hormone receptor (TSHR antagonist effect.
Full Text Available Alzheimer’s Disease (AD is the most common cause of dementia, affecting approximately two thirds of the 35 million people worldwide with the condition. Despite this, effective treatments are lacking, and there are no drugs that elicit disease modifying effects to improve outcome. There is an urgent need to develop and evaluate more effective pharmacological treatments. Drug repositioning offers an exciting opportunity to repurpose existing licensed treatments for use in AD, with the benefit of providing a far more rapid route to the clinic than through novel drug discovery approaches. This review outlines the current most promising candidates for repositioning in AD, their supporting evidence and their progress through trials to date. Furthermore, it begins to explore the potential of new transcriptomic and microarray techniques to consider the future of drug repositioning as a viable approach to drug discovery.
Li, Jiao; Zheng, Si; Chen, Bin; Butte, Atul J; Swamidass, S Joshua; Lu, Zhiyong
Computational drug repositioning or repurposing is a promising and efficient tool for discovering new uses from existing drugs and holds the great potential for precision medicine in the age of big data. The explosive growth of large-scale genomic and phenotypic data, as well as data of small molecular compounds with granted regulatory approval, is enabling new developments for computational repositioning. To achieve the shortest path toward new drug indications, advanced data processing and analysis strategies are critical for making sense of these heterogeneous molecular measurements. In this review, we show recent advancements in the critical areas of computational drug repositioning from multiple aspects. First, we summarize available data sources and the corresponding computational repositioning strategies. Second, we characterize the commonly used computational techniques. Third, we discuss validation strategies for repositioning studies, including both computational and experimental methods. Finally, we highlight potential opportunities and use-cases, including a few target areas such as cancers. We conclude with a brief discussion of the remaining challenges in computational drug repositioning. Published by Oxford University Press 2015. This work is written by US Government employees and is in the public domain in the US.
Elias, Fadia; Khuri, Fadlo R; Adib, Salim M; Karam, Rita; Harb, Hilda; Awar, May; Zalloua, Pierre; Ammar, Walid
The Ministry of Public Health (MOPH) in Lebanon provides cancer drugs free of charge for uninsured patients who account for more than half the total caseload. Other categories of cancer care are subsidized under more stringent eligibility criteria. MOPH's large database offers an excellent opportunity to analyze the cost of cancer treatment in Lebanon. Using utilization and spending data accumulated at MOPH during 20082013, the cost to the public budget of cancer drugs was assessed per case and per drug type. The average annual cost of cancer drugs was 6,475$ per patient. Total cancer drug costs were highest for breast cancer, followed by chronic myeloid leukemia (CML), colorectal cancer, lung cancer, and NonHodgkin's lymphoma (NHL), which together represented 74% of total MOPH cancer drug expenditure. The annual average cancer drug cost per case was highest for CML ($31,037), followed by NHL ($11,566). Trastuzumab represented 26% and Imatinib 15% of total MOPH cancer drug expenditure over six years. Sustained increase in cancer drug cost threatens the sustainability of MOPH coverage, so crucial for socially vulnerable citizens. To enhance the bargaining position with pharmaceutical firms for drug cost containment in a small market like Lebanon, drug price comparisons with neighboring countries which have already obtained lower prices may succeed in lowering drug costs.
Aimoto, Takayuki; Uchida, Eiji; Nakamura, Yoshiharu; Yamahatsu, Kazuya; Matsushita, Akira; Katsuno, Akira; Cho, Kazumitsu; Kawamoto, Masao
Chronic pancreatitis (CP) is a painful, yet benign inflammatory process of the pancreas. Surgical management should be individualized because the pain is multifactorial and its mechanisms vary from patient to patient. Two main pathogenetic theories for the mechanisms of pain in CP have been proposed: the neurogenic theory and the theory of increased intraductal/intraparenchymal pressures. The latter theory is strongly supported by the good results of drainage procedures in the surgical management of CP. Other possible contributing factors include pancreatic ischemia; a centrally sensitized pain state; and the development of complications, such as pseudocysts and stenosis of the duodenum or common bile duct. Common indications for surgery include intractable pain, suspicion of neoplasm, and complications that cannot be resolved with radiological or endoscopic treatments. Operative procedures have been historically classified into 4 categories: decompression procedures for diseased and obstructed pancreatic ducts; resection procedures for the proximal, distal, or total pancreas; denervation procedures of the pancreas; and hybrid procedures. Pancreaticoduodenectomy and pylorus-preserving pancreaticoduodenectomy, once the standard operations for patients with CP, have been replaced by hybrid procedures, such as duodenum-preserving pancreatic head resection, the Frey procedure, and their variants. These procedures are safe and effective in providing long-term pain relief and in treating CP-related complications. Hybrid procedures should be the operations of choice for patients with CP.
Griffel, L H; Das, K M
Ulcerative colitis is a chronic inflammatory disease of the colon that affects the rectum and a variable length of contiguous colon. The disease is characterized by rectal bleeding and diarrhea during periods of exacerbation; these symptoms usually abate with treatment. The pathogenic mechanism of ulcerative colitis is believed to be an aberrant immune response in which antibodies are formed against colonic epithelial protein(s). The disease usually presents during the second and third decades of life, with a smaller peak after the age of 60 years. There is a genetic component to ulcerative colitis, with a higher incidence among family members and, particularly, first-degree relatives. Diagnosis depends on several factors, most notably symptoms, demonstration of uniformly inflamed mucosa beginning in the rectum, and exclusion of other causes of colitis, such as infection. There is no medical cure for ulcerative colitis, but medical therapy is effective and can improve or eliminate symptoms in more than 80% of patients. Surgery offers a cure but carries the high price of total colectomy. New surgical methods, such as ileoanal anastomosis, allow for maintenance of bowel continuity and better patient satisfaction.
Fischer, Jan; Neale, Joanne; Bloor, Michael; Jenkins, Nicholas
This paper examines client/staff conflict and user involvement in drug misuse treatment decision-making. Seventy-nine in-depth interviews were conducted with new treatment clients in two residential and two community drug treatment agencies. Fifty-nine of these clients were interviewed again after twelve weeks. Twenty-seven interviews were also conducted with staff, who were the keyworkers for the interviewed clients. Drug users did not expect, desire or prepare for conflict at treatment entry. They reported few actual conflicts within the treatment setting, but routinely discussed latent conflicts--that is, negative experiences and problematic aspects of current or previous treatment that could potentially escalate into overt disputes. Conflict resulted in a number of possible outcomes, including the premature termination of treatment; staff deciding on the appropriate outcome; the client appealing to the governance structure of the agency; brokered compromise; and staff skilfully eliciting client consent for staff decisions. Although the implementation of user involvement in drug treatment decision-making has the potential to trigger high levels of staff-client conflict, latent conflict is more common than overt conflict and not all conflict is negative. Drug users generally want to be co-operative at treatment entry and often adopt non-confrontational forms of covert resistance to decisions about which they disagree. Staff sometimes deploy user involvement as a strategy for managing conflict and soliciting client compliance to treatment protocols. Suggestions for minimising and avoiding harmful conflict in treatment settings are given.
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...
Thorup, Lene; Simonsen, Ulf; Grimm, Daniela; Hedegaard, Elise R
In heart failure (HF), the heart cannot pump blood efficiently and is therefore unable to meet the body's demands of oxygen, and/or there is increased end-diastolic pressure. Current treatments for HF with reduced ejection fraction (HFrEF) include angiotensin-converting enzyme (ACE) inhibitors, angiotension receptor type 1 (AT 1 ) antagonists, β-adrenoceptor antagonists, aldosterone receptor antagonists, diuretics, digoxin and a combination drug with AT 1 receptor antagonist and neprilysin inhibitor. In HF, the risk of readmission for hospital and mortality is markedly higher with a heart rate (HR) above 70 bpm. Here, we review the evidence regarding the use of ivabradine for lowering HR in HF. Ivabradine is a blocker of an I funny current (I(f)) channel and causes rate-dependent inhibition of the pacemaker activity in the sinoatrial node. In clinical trials of HFrEF, treatment with ivabradine seems to improve clinical outcome, for example improved ejection fraction (EF) and less readmission for hospital, but the effect appears most pronounced in patients with HRs above 70 bpm, while the effect on cardiovascular death appears less consistent. The adverse effects of ivabradine include bradycardia, atrial fibrillation and visual disturbances, but ivabradine avoids the negative inotrope effects observed with β-adrenoceptor antagonists. In conclusion, in patients with stable HFrEF with EF<35% and HR above 70 bpm, ivabradine improves the outcome and might be a first choice of therapy, if beta-adrenoceptor antagonists are not tolerated. Further studies must show whether that can be extended to HF patients with preserved EF. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
Jiang, Wei; Wang, Xuefeng; Zhou, Shengnian
Rhabdomyolysis syndrome refers to a variety of factors that affect the striated muscle cell membrane, the membrane channels and its energy supply. Most cases of rhabdomyolysis are due to direct trauma. However, infection, toxins, drugs, muscle ischemia, electrolyte imbalance, metabolic diseases, genetic diseases and abnormal body temperature can also lead to rhabdomyolysis. Epilepsy is one of the most common chronic neurological diseases. The primary long-term treatment is antiepileptic drugs (AEDs), which may cause rhabdomyolysis. This article summarizes the characteristics, treatment methods and prognosis of patients with rhabdomyolysis that is induced by antiepileptic drugs. This review is based on PubMed, EMBASE and MEDLINE searches of the literature using the keywords "epilepsy", "antiepileptic drugs","status epilepticus","rhabdomyolysis", and "antiepileptic drugs and rhabdomyolysis syndrome" as well as extensive personal clinical experience with various antiepileptic drugs. Potential relationships between antiepileptic drugs and rhabdomyolysis are discussed. Worldwide, there are approximately 50 million epilepsy patients, most of whom are treated with drugs. Reports have indicated that the majority of antiepileptic drugs on the market can cause rhabdomyolysis. Although rhabdomyolysis induced by antiepileptic drugs is a rare condition with a low incidence, this condition has serious consequences and merits attention from clinicians.
Lega, Sara; Bramuzzo, Matteo; Dubinsky, Marla
As the paradigm for IBD management is evolving from symptom control to the more ambitious goal of complete deep remission, the concept of personalized medicine, as a mean to deliver individualized treatment with the best effectiveness and safety profile, is becoming paramount. Therapeutic drug monitoring (TDM) is an essential part of personalized medicine wherein serum drug concentrations are used to guide drug dosing on an individual basis. The concept of TDM has been introduced in the field of IBD along with thiopurines, over a decade ago, and evolved around anti-TNFs therapies. In the era of biologics, TDM entered the clinical field to assist clinicians managing anti-TNF failure and its role is now moving toward the concept of "proactive" TDM with the goal to optimize drug exposure and prevent loss of response. Research in TDM is rapidly expanding: while the role of TDM with new biologics is under investigation, preliminary data suggest that software-systems support tools could be an opportunity to guide dosing choices and maximize the cost-benefit profile of therapies in the near future. The review discusses the current knowledge that poses the rationale for the use of TDM and the present and future role of TDM-based approaches in the management of pediatric IBD. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Sideroff, Stephen I.
Presents a Gestalt therapeutic approach that has shown promise within a drug treatment program. The major issues discussed include the acquisition of self-support, taking responsibility, dealing with anxiety, contact, and the expression of pent-up feelings. (Author)
van Durme, Caroline M. P. G.; Wechalekar, Mihir D.; Landewé, Robert B. M.
Are nonsteroidal anti-inflammatory drugs (NSAIDs) associated with better outcomes than cyclooxygenase inhibitors, glucocorticoids, IL-1 inhibitors or placebo in the treatment of acute gout? NSAIDs are not significantly associated with a difference in pain reduction compared with cyclooxygenase
Bosque-Prous, Marina; Brugal, María Teresa
Harm reduction encompasses interventions, programmes and policies that seek to reduce the negative consequences of the consumption of both legal and illegal drugs on the individual and public health. Harm reduction looks to mitigate the harm suffered by drug users through drug use monitoring and prevention, and promotes initiatives that respect and protect the human rights of this population. The harm reduction policies that have proven effective and efficient are: opioid substitution maintenance therapy (methadone); needle and syringe exchange programmes; supervised drug consumption rooms; and overdose prevention through peer-based naloxone distribution. In order to be effective, these policies must have comprehensive coverage and be implemented in areas where the target population is prevalent. Resident-based opposition to the implementation of these policies is known as the NIMBY (Not In My Back Yard) phenomenon, which is characterised by being against the implementation of new measures in a particular place, but does not question their usefulness. Given that any NIMBY phenomenon is a complex social, cultural and political phenomenon, it is important to conduct a thorough analysis of the situation prior to implementing any of these measures. Harm reduction policies must be extended to other substances such as alcohol and tobacco, as well as to other conditions beyond infectious/contagious diseases and overdose. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.
Obesity will continue to be one of the leading causes of chronic disease unless the ongoing rise in the prevalence of this condition is reversed. Accumulating morbidity figures and a shortage of effective drugs have generated substantial research activity with several molecular targets being
Evans, Suzette M; Reynolds, Brady
This special issue exemplifies one of the major goals of the current editor of Experimental and Clinical Psychopharmacology (Dr. Suzette Evans): to increase the number of manuscripts that emphasize females and address sex differences. Taken together, these articles represent a broad range of drug classes and approaches spanning preclinical research to treatment to better understand the role of sex differences in drug abuse. While not all studies found sex differences, we want to emphasize that finding no sex difference is just as important as confirming one, and should be reported in peer-reviewed journals. It is our intention and hope that this special issue will further advance scientific awareness about the importance of accounting for sex differences in the study of substance abuse. Participant sex is an essential variable to consider in developing a more comprehensive understanding of substance abuse. Rather than viewing investigating sex differences as burdensome, investigators should seize this opportune area ripe for innovative research that is long overdue. (c) 2015 APA, all rights reserved).
Full Text Available In this article we describe the key role of tuberculosis (TB treatment, the challenges (mainly the emergence of drug resistance, and the opportunities represented by the correct approach to drug dosage, based on the existing control and elimination strategies. In this context, the role and contribution of therapeutic drug monitoring (TDM is discussed in detail. Treatment success in multidrug-resistant (MDR TB cases is low (62%, with 7% failing or relapsing and 9% dying and in extensively drug-resistant (XDR TB cases is even lower (40%, with 22% failing or relapsing and 15% dying. The treatment of drug-resistant TB is also more expensive (exceeding €50 000 for MDR-TB and €160 000 for XDR-TB and more toxic if compared to that prescribed for drug-susceptible TB. Appropriate dosing of first- and second-line anti-TB drugs can improve the patient's prognosis and lower treatment costs. TDM is based on the measurement of drug concentrations in blood samples collected at appropriate times and subsequent dose adjustment according to the target concentration. The ‘dried blood spot’ technique offers additional advantages, providing the rationale for discussions regarding a possible future network of selected, quality-controlled reference laboratories for the processing of dried blood spots of difficult-to-treat patients from reference TB clinics around the world.
Kolind, Torsten; Frank, Vibeke Asmussen; Dahl, Helle
The availability of prison-based drug treatment has increased markedly throughout Europe over the last 15 years in terms of both volume and programme diversity. However, prison drug treatment faces problems and challenges because of the tension between ideologies of rehabilitation and punishment. This article reports on a study of four cannabis treatment programmes and four psychosocial drug treatment programmes in four Danish prisons during 2007. The data include the transcripts of 22 semi-structured qualitative interviews with counsellors and prison employees, prison statistics, and information about Danish laws and regulations. These treatment programmes reflect the 'treatment guarantee' in Danish prisons. However, they are simultaneously embedded in a new policy of zero tolerance and intensified disciplinary sanctions. This ambivalence is reflected in the experiences of treatment counsellors: reluctantly, they feel associated with the prison institution in the eyes of the prisoners; they experience severe opposition from prison officers; and the official goals of the programmes, such as making clients drug free and preparing them for a life without crime, are replaced by more pragmatic aims such as alleviating the pain of imprisonment felt by programme clients. The article concludes that at a time when prison-based drug treatment is growing, it is crucial that we thoroughly research and critically discuss its content and the restrictions facing such treatment programmes. One way of doing this is through research with counsellors involved in delivering drug treatment services. By so doing, the programmes can become more pragmatic and focused, and alternatives to prison-based drug treatment can be seriously considered.
This article is exploring different forms of constraint that are exerted in the field of drug addiction treatment. The objective of this article is to establish benchmarks and to stimulate reflection about the ethical and clinical implications of those constraints in the field of drug addiction treatment. This article is presenting a critical review of different forms of constraint that can be exerted in Canada in regard to the treatment of drug addiction. In the first section of the article, a definition of therapeutic intervention is proposed, that includes the dimension of power, which justifies the importance of considering the coercive aspects of treatment. The second section, which represents the core section of the paper, is devoted to the presentation of different levels of constraint that can be distinguished in regard to drug addicts who are under treatment. Three levels of constraint are exposed: judicial constraint, institutional constraint and relational constraint. The coercive aspect of treatment can then be recognized as a combination of all tree levels of constraint. Judicial constraint refers to any form of constraint in which the court or the judge is imposing or recommending treatment. This particular level of constraint can take different forms, such as therapeutic remands, conditions of a probation order, conditions of a conditional sentence of imprisonment, and coercive treatment such as the ones provided through drug courts. Institutional constraint refers to any form of constraint exerted within any institutional setting, such as correctional facilities and programs offered in community. Correctional facilities being limited by their own specific mission, it might have a major impact on the way the objectives of treatment are defined. Those limitations can then be considered as a form of constraint, in which drug users don't have much space to express their personal needs. Finally, relational constraint refers to any form of constraint in
Pringle, Abbie; Harmer, Catherine J
Human models of emotional processing suggest that the direct effect of successful antidepressant drug treatment may be to modify biases in the processing of emotional information. Negative biases in emotional processing are documented in depression, and single or short-term dosing with conventional antidepressant drugs reverses these biases in depressed patients prior to any subjective change in mood. Antidepressant drug treatments also modulate emotional processing in healthy volunteers, which allows the consideration of the psychological effects of these drugs without the confound of changes in mood. As such, human models of emotional processing may prove to be useful for testing the efficacy of novel treatments and for matching treatments to individual patients or subgroups of patients.
Ferris, G N
Psychotropic drug treatment of persons on methadone maintenance is discussed. Patients with clear target symptoms, such as anxiety, depression, or psychosis responded just as non-opioid addicts would to the major psychotropic agents. The minor tranquilizers are felt to be of doubtful value, and subject to abuse. Sleep disturbances cannot be treated by the usual means, as the drugs needed again are abused. However, chlorpromazine shows some promise here. Methods of drug delivery and goals of treatment must be adapted to the realities of this patient-group's characteristics, particularly anti-social traits, poor motivation and unreliability. Psychotropic drugs are unlikely to be of aid in multiple drug abusers, personality and character disorders, and opioid withdrawal. Four case histories are presented.
Full Text Available The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain, the patients’ age, comorbidities, and appropriate choice of analgesic, its dose and route of administration. This review is aimed at presenting current knowledge on analgesics administered by transdermal and topical routes for physicians, nurses, pharmacists, and other health care professionals dealing with patients suffering from pain. Analgesics administered transdermally or topically act through different mechanisms. Opioids administered transdermally are absorbed into vessels located in subcutaneous tissue and, subsequently, are conveyed in the blood to opioid receptors localized in the central and peripheral nervous system. Non–steroidal anti–inflammatory drugs (NSAIDs applied topically render analgesia mainly through a high concentration in the structures of the joint and a provision of local anti–inflammatory effects. Topically administered drugs such as lidocaine and capsaicin in patches, capsaicin in cream, EMLA cream, and creams containing antidepressants (i.e., doxepin, amitriptyline act mainly locally in tissues through receptors and/or ion channels. Transdermal and topical routes offer some advantages over systemic analgesic administration. Analgesics administered topically have a much better profile for adverse effects as they relieve local pain with minimal systemic effects. The transdermal route apart from the above-mentioned advantages and provision of long period of analgesia may be more convenient, especially for patients who are unable to take drugs orally. Topically and transdermally administered opioids are characterised by a lower risk of addiction compared to oral and parenteral routes.
Pritz, Stephan; Doering, Klaus; Woelcke, Julian; Hassiepen, Ulrich
Fluorescence lifetime assays complement the portfolio of established assay formats available in drug discovery, particularly with the recent advances in microplate readers and the commercial availability of novel fluorescent labels. Fluorescence lifetime assists in lowering complexity of compound screening assays, affording a modular, toolbox-like approach to assay development and yielding robust homogeneous assays. To date, materials and procedures have been reported for biochemical assays on proteases, as well as on protein kinases and phosphatases. This article gives an overview of two assay families, distinguished by the origin of the fluorescence signal modulation. The pharmaceutical industry demands techniques with a robust, integrated compound profiling process and short turnaround times. Fluorescence lifetime assays have already helped the drug discovery field, in this sense, by enhancing productivity during the hit-to-lead and lead optimization phases. Future work will focus on covering other biochemical molecular modifications by investigating the detailed photo-physical mechanisms underlying the fluorescence signal.
Albengres, E; Gauthier, F; Tillement, J P
The French system of drug surveillance is characterized by several original features: thirty regional centres are selected to cover all of France to collect, analyze and enter the adverse drug events in the national data bank. The system is based on a bank of well documented files submitted to a decision of imputation; the report of severe events by prescribers is mandatory; cases are collected either by spontaneous reporting (routine) or by direct request (intensive validation study); the system is being involved in studies of epidemiological type as carried out by the national system of health or a few societies of medicine as well as by the centres themselves in cooperative works on defined populations.
Rosenfeldt, Hans; Kropp, Timothy; Benson, Kimberly; Ricci, M. Stacey; McGuinn, W. David; Verbois, S. Leigh
The drug development of new anti-cancer agents is streamlined in response to the urgency of bringing effective drugs to market for patients with limited life expectancy. FDA's regulation of oncology drugs has evolved from the practices set forth in Arnold Lehman's seminal work published in the 1950s through the current drafting of a new International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) safety guidance for anti-cancer drug nonclinical evaluations. The ICH combines the efforts of the regulatory authorities of Europe, Japan, and the United States and the pharmaceutical industry from these three regions to streamline the scientific and technical aspects of drug development. The recent development of new oncology drug classes with novel mechanisms of action has improved survival rates for some cancers but also brings new challenges for safety evaluation. Here we present the legacy of Lehman and colleagues in the context of past and present oncology drug development practices and focus on some of the current issues at the center of an evolving harmonization process that will generate a new safety guidance for oncology drugs, ICH S9. The purpose of this new guidance will be to facilitate oncology drug development on a global scale by standardizing regional safety requirements.
Kapoor, Mamta; Lee, Sau L; Tyner, Katherine M
Research in the area of liposomes has grown substantially in the past few decades. Liposomes are lipid bilayer structures that can incorporate drug substances to modify the drug's pharmacokinetic profile thereby improving drug delivery. The agency has received over 400 liposomal drug product submissions (excluding combination therapies), and there are currently eight approved liposomal drug products on the US market. In order to identify the pain points in development and manufacturing of liposomal drug products, a retrospective analysis was performed from a quality perspective on submissions for new and generic liposomal drug products. General analysis on liposomal drug product submissions was also performed. Results indicated that 96% of the submissions were Investigational New Drug (IND) applications, 3% were New Drug Applications (NDAs), and the remaining 1% was Abbreviated New Drug Applications (ANDAs). Doxorubicin hydrochloride was the most commonly used drug substance incorporated into the liposomes (31%). The majority of the liposomal products were administered via intravenous route (84%) with cancer (various types) being the most common indication (63%). From a quality perspective, major challenges during the development of liposomal drug products included identification and (appropriate) characterization of critical quality attributes of liposomal drug products and suitable control strategies during product development. By focusing on these areas, a faster and more efficient development of liposomal drug products may be achieved. Additionally, in this way, the drug review process for such products can be streamlined.
Full Text Available The emergence and spread of drug resistant malaria represents a considerable challenge to controlling malaria. To date, malaria control has relied heavily on a comparatively small number of chemically related drugs, belonging to either the quinoline or the antifolate groups. Only recently have the artemisinin derivatives been used but mostly in south east Asia. Experience has shown that resistance eventually curtails the life-span of antimalarial drugs. Controlling resistance is key to ensuring that the investment put into developing new antimalarial drugs is not wasted. Current efforts focus on research into new compounds with novel mechanisms of action, and on measures to prevent or delay resistance when drugs are introduced. Drug discovery and development are long, risky and costly ventures. Antimalarial drug development has traditionally been slow but now various private and public institutions are at work to discover and develop new compounds. Today, the antimalarial development pipeline is looking reasonably healthy. Most development relies on the quinoline, antifolate and artemisinin compounds. There is a pressing need to have effective, easy to use, affordable drugs that will last a long time. Drug combinations that have independent modes of action are seen as a way of enhancing efficacy while ensuring mutual protection against resistance. Most research work has focused on the use of artesunate combined with currently used standard drugs, namely, mefloquine, amodiaquine, sulfadoxine/pyrimethamine, and chloroquine. There is clear evidence that combinations improve efficacy without increasing toxicity. However, the absolute cure rates that are achieved by combinations vary widely and depend on the level of resistance of the standard drug. From these studies, further work is underway to produce fixed dose combinations that will be packaged in blister packs. This review will summarise current antimalarial drug developments and outline recent
Full Text Available The causes of drug abuse and criminal behavior are closely linked. Not surprisingly, there is a high percentage of prisoners who during sentence execution abuse or are dependent on drugs. Antisocial personality disorder can be considered a common predictor of committing criminal offenses and drug abuse. A review of studies has revealed a high prevalence of inmates who use drugs while serving a sentence. Also, prison environment represents only a new context of the continuum of drug abuse by inmates. There are different theoretical approaches in explaining this phenomenon. Treatment programs based on empirically validated principles that guarantee the effectiveness, may be one strategy for solving the problem of drug abuse in prisons, with multiple positive effects.
Taxman, Faye S.; Bouffard, Jeffrey A.
Drug treatment is one of the critical components of drug court programming, yet it has not been thoroughly studied in the drug court literature. Very little is understood about the nature of drug treatment services provided in the drug court setting. The purpose of this study was to examine the effects of selected treatment variables on drug court…
Alzheimer’s disease is a currently incurable neurodegenerative disorder, and its treatment has posed a big challenge. Proposed causes of Alzheimer’s disease include the cholinergic, amyloid and tau hypothesis. Current therapeutic treatments have been aimed at dealing with neurotransmitter imbalance. These include cholinesterase inhibitors and N-methyl D-aspartate receptor antagonists. However, current therapeutics have been unable to halt its progression. The future of Alzheimer’s disease tre...
Full Text Available Nanoparticles combined with cells, drugs, and specially designed genes provide improved therapeutic efficacy in studies and clinical setting, demonstrating a new era of treatment strategy, especially in retinal diseases. Nanotechnology-based drugs can provide an essential platform for sustaining, releasing and a specific targeting design to treat retinal diseases. Poly-lactic-co-glycolic acid is the most widely used biocompatible and biodegradable polymer approved by the Food and Drug Administration. Many studies have attempted to develop special devices for delivering small-molecule drugs, proteins, and other macromolecules consistently and slowly. In this article, we first review current progress in the treatment of age-related macular degeneration. Then, we discuss the function of vascular endothelial growth factor (VEGF and the pharmacological effects of anti-VEGF-A antibodies and soluble or modified VEGF receptors. Lastly, we summarize the combination of antiangiogenic therapy and nanomedicines, and review current potential targeting therapy in age-related macular degeneration.
Cunningham, J A; Sobell, L C; Sobell, M B; Gaskin, J
Clients at two different treatment facilities were asked at assessment how influential each of 10 possible reasons were in their decision to change their alcohol or drug use. Clients at both facilities most often endorsed "weighing the pros and cons of drinking or drug use" and a "warning from spouse." Client's reasons for seeking treatment were also examined in relation to treatment compliance. Three reasons--"weighing the pros and cons," "hitting rock bottom," and experiencing a "major lifestyle change"--were predictive of treatment compliance. Clients who rated any of these reasons as influential were more likely to enter and complete treatment. Although more research is needed, knowledge of clients' reasons for seeking treatment might be useful in treatment matching.
de Roode, Jacobus C; Culleton, Richard; Bell, Andrew S; Read, Andrew F
Malaria infections are often genetically diverse, potentially leading to competition between co-infecting strains. Such competition is of key importance in the spread of drug resistance. The effects of drug treatment on within-host competition were studied using the rodent malaria Plasmodium chabaudi. Mice were infected simultaneously with a drug-resistant and a drug-sensitive clone and were then either drug-treated or left untreated. Transmission was assessed by feeding mice to Anopheles stephensi mosquitoes. In the absence of drugs, the sensitive clone competitively suppressed the resistant clone; this resulted in lower asexual parasite densities and also reduced transmission to the mosquito vector. Drug treatment, however, allowed the resistant clone to fill the ecological space emptied by the removal of the sensitive clone, allowing it to transmit as well as it would have done in the absence of competition. These results show that under drug pressure, resistant strains can have two advantages: (1) they survive better than sensitive strains and (2) they can exploit the opportunities presented by the removal of their competitors. When mixed infections are common, such effects could increase the spread of drug resistance.
... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Non-residential drug abuse treatment... INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Abuse Treatment Program § 550.52 Non-residential drug abuse treatment services. All institutions must have non-residential drug abuse treatment services, provided...
Sarang, Anya; Rhodes, Tim; Sheon, Nicolas
Achieving 'universal access' to antiretroviral HIV treatment (ART) in lower income and transitional settings is a global target. Yet, access to ART is shaped by local social condition and is by no means universal. Qualitative studies are ideally suited to describing how access to ART is socially situated. We explored systemic barriers to accessing ART among people who inject drugs (PWID) in a Russian city (Ekaterinburg) with a large burden of HIV treatment demand. We undertook 42 in-depth qualitative interviews with people living with HIV with current or recent experience of injecting drug use. Accounts were analysed thematically, and supplemented here with an illustrative case study. Three core themes were identified: 'labyrinthine bureaucracy' governing access to ART; a 'system Catch 22' created by an expectation that access to ART was conditional upon treated drug use in a setting of limited drug treatment opportunity; and 'system verticalization', where a lack of integration across HIV, tuberculosis (TB) and drug treatment compromised access to ART. Taken together, we find that systemic factors play a key role in shaping access to ART with the potential adverse effects of reproducing treatment initiation delay and disengagement from treatment. We argue that meso-level systemic factors affecting access to ART for PWID interact with wider macro-level structural forces, including those related to drug treatment policy and the social marginalization of PWID. We note the urgent need for systemic and structural changes to improve access to ART for PWID in this setting, including to simplify bureaucratic procedures, foster integrated HIV, TB and drug treatment services, and advocate for drug treatment policy reform.
Libretto, Salvatore; Nemes, Susanna; Namur, Jenny; Garrett, Gerald; Hess, Lauren; Kaplan, Linda
In a study to evaluate the drug treatment and aftercare efforts sponsored by the State Department's International Narcotics and Law Enforcement Affairs Bureau, residential Therapeutic Community (TC) treatment programs in three countries in Southeast Asia--Malaysia, Singapore, and Thailand--were examined to identify promising practices and to…
Examined the sex-role attitude of the drug abuse treatment counselor. Found: 1) male counselors viewed clients of both sexes more negatively; 2) male clients were viewed more negatively by counselors of both sexes; 3) counselors with less education had more negative attitudes; and 4) attitudes differed with treatment program type. (Author/RC)
Prajapati, Vipul D; Jani, Girish K; Kapadia, Jinita R
Biodegradable microspheres have gained popularity for delivering a wide variety of molecules via various routes. These types of products have been prepared using various natural and synthetic biodegradable polymers through suitable techniques for desired delivery of various challenging molecules. Selection of biodegradable polymers and technique play a key role in desired drug delivery. This review describes an overview of the fundamental knowledge and status of biodegradable microspheres in effective delivery of various molecules via desired routes with consideration of outlines of various compendial and non-compendial biodegradable polymers, formulation techniques and release mechanism of microspheres, patents and commercial biodegradable microspheres. There are various advantages of using biodegradable polymers including promise of development with different types of molecules. Biocompatibility, low dosage and reduced side effects are some reasons why usage biodegradable microspheres have gained in popularity. Selection of biodegradable polymers and formulation techniques to create microspheres is the biggest challenge in research. In the near future, biodegradable microspheres will become the eco-friendly product for drug delivery of various genes, hormones, proteins and peptides at specific site of body for desired periods of time.
Wasserman, Sean; Meintjes, Graeme; Maartens, Gary
Linezolid is an oxazolidinone with potent activity against M tuberculosis, and improves culture conversion and cure rates when added to treatment regimens for drug resistant tuberculosis. However, linezolid has a narrow therapeutic window, and the optimal dosing strategy that minimizes the substantial toxicity associated with linezolid's prolonged use in tuberculosis treatment has not been determined, limiting the potential impact of this anti-mycobacterial agent. This paper aims to review and summarize the current knowledge on linezolid for the treatment of drug-resistant tuberculosis. The focus is on the pharmacokinetic-pharmacodynamic determinants of linezolid's efficacy and toxicity in tuberculosis, and how this relates to defining an optimal dose. Mechanisms of linezolid toxicity and resistance, and the potential role of therapeutic drug monitoring are also covered. Expert commentary: Prospective pharmacokinetic-pharmacodynamic studies are required to define optimal therapeutic targets and to inform improved linezolid dosing strategies for drug-resistant tuberculosis.
Malcolm J. Reid
Full Text Available Over the past few years the analysis of drug residues in sewage has been promoted as a means of estimating the level of drug use in communities. Measured drug residue concentrations in the sewage are used to determine the load (total mass of the drug being used by the entire community. Knowledge of the size or population of the community then allows for the calculation of drug-use relative to population (typically drug-mass/day/1000 inhabitants which facilitates comparisons between differing communities or populations. Studies have been performed in many European countries, including Norway, as well as in the US and Australia. The approach has successfully estimated the use of cocaine, amphetamine, methamphetamine, MDMA, cannabis, nicotine and alcohol. The analysis of biomarkers of drug use in sewage has great potential to support and complement existing techniques for estimating levels of drug use, and as such has been identified as a promising development by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA; www.emcdda.europa.eu/wastewater-analysis. The approach is not without its challenges, and ongoing collaboration across Europe aims at agreeing upon best-practice and harmonising the methods being used. In Norway development is being performed through the NFR RUSMIDDEL funded DrugMon (www.niva.no/drugmon project that has led to the development of many new techniques, significantly improved our understanding of the uncertainties associated with the approach and allowed the coordination of Europe wide collaboration which has included all important intercalibration exercises. Application of the technique can provide evidence-based and real-time estimates of collective drug use with the resulting data used to improve the much needed estimates of drug use and dependency.
Aly, Lilian; Hemmer, Bernhard; Korn, Thomas
Immunosuppressive drugs have been used in the treatment of multiple sclerosis (MS) for a long time. Today, orally available second generation immunosuppressive agents have been approved or are filed for licensing as MS therapeutics. Due to semi-selective targeting of cellular processes, these second-generation immunosuppressive compounds might rather be immunomodulatory. For example, Teriflunomide inhibits the de novo pyrimidine synthesis and thus only targets rapidly proliferating cells, including lymphocytes. It is used as first line disease modifying therapy (DMT) in relapsing-remitting MS (RRMS). Review of online content related to oral immunosuppressants in MS with an emphasis on Teriflunomide. Teriflunomide and Cladribine are second-generation immunosuppressants that are efficient in the treatment of MS patients. For Teriflunomide, a daily dose of 14 mg reduces the annualized relapse rate (ARR) by more than 30% and disability progression by 30% compared to placebo. Cladribine reduces the ARR by about 50% compared to placebo but has not yet been licensed due to unresolved safety concerns. We also discuss the significance of older immunosuppressive compounds including Azathioprine, Mycophenolate mofetile, and Cyclophosphamide in current MS therapy. Teriflunomide has shown a favorable safety and efficacy profile in RRMS and is a therapeutic option for a distinct group of adult patients with RRMS. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Wager, L A; Linquist, W E; Hayes, G L; Britten, A M; Whitehead, R G; Webster, D E; Barnes, F D
Mastitis in its complexity has managed to forestall all efforts of eradication in spite of years of research, antibiotics and practical control measures. This minisymposium will touch on seven topics current to treatment and control of this economically important disease.
El Matri L
Full Text Available Leila El Matri, Ahmed Chebil, Fedra Kort Department B of Ophthalmology, Hedi Rais Institute of Ophthalmology, Faculty of Medicine of Tunis, University of El Manar, Tunis, Tunisia Abstract: Choroidal neovascularization (CNV is the main cause of visual impairment in highly myopic patients younger than 50 years of age. There are different treatments for myopic CNV (mCNV, with 5- to 10-year outcomes currently. Chorioretinal atrophy is still the most important determinant factor for visual outcome. The purpose of this study is to provide an overview of the current treatments for mCNV, including laser, surgical management, verteporfin photodynamic therapy, and mainly anti-vascular endothelial growth factor therapy. Emerging treatment options are also discussed. Keywords: myopia, choroidal neovascularization, current treatment, emerging treatment
Workowski, Eric J.
This study examined the relationship between criminal violence and type of substance abuse among 184 current and former residents of an inpatient non-hospital drug and alcohol treatment facility. The criminal justice system functioned as the source of referral into the program for 89% of the subjects studied while only 11% came to treatment…
Richelsen, Rasmus Kapalu Broge; Overvad, Thure Filskov; Jensen, Svend Eggert
Drug-eluting balloons (DEBs) have emerged as a new application in percutaneous coronary intervention. DEBs have proven successful in the treatment of in-stent restenosis, but their role in de novo lesions is less clear. This paper provides a review of the current studies where DEBs have been used...
Full Text Available Di Wu, Mengjie Si, Hui-Yi Xue, Ho-Lun Wong Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA Abstract: Breast cancer is the most common malignant disease in women worldwide, but the current drug therapy is far from optimal as indicated by the high death rate of breast cancer patients. Nanomedicine is a promising alternative for breast cancer treatment. Nanomedicine products such as Doxil® and Abraxane® have already been extensively used for breast cancer adjuvant therapy with favorable clinical outcomes. However, these products were originally designed for generic anticancer purpose and not specifically for breast cancer treatment. With better understanding of the molecular biology of breast cancer, a number of novel promising nanotherapeutic strategies and devices have been developed in recent years. In this review, we will first give an overview of the current breast cancer treatment and the updated status of nanomedicine use in clinical setting, then discuss the latest important trends in designing breast cancer nanomedicine, including passive and active cancer cell targeting, breast cancer stem cell targeting, tumor microenvironment-based nanotherapy and combination nanotherapy of drug-resistant breast cancer. Researchers may get insight from these strategies to design and develop nanomedicine that is more tailored for breast cancer to achieve further improvements in cancer specificity, antitumorigenic effect, antimetastasis effect and drug resistance reversal effect. Keywords: nanomedicine, breast cancer, targeted delivery, drug therapy, drug resistance, tumor microenvironment
Full Text Available Background: Alzheimer’s disease (AD that is identified by progressive cognitive deficit and behavioral disturbances (BD are the most common form of dementia. As the population is aging, patients with AD are becoming a serious burden for societies. In this study, current medication for cognitive deficit and behavioral disturbances are reviewed. Also the new treatment strategies for cognitive dysfunction and behavioral disturbances are surveyed. Methods: The method employed in this researh was a systematic bibliographic review, in which only the double-blind placebo-controlled studies or the clinically detailed enough open-labeled studies using validated scales were retained. Results: The efficacy of cholinesterase inhibitors (Tacrine, Rivastigmine, Donapezil and Galantamine has been demonstrated in several double blind placebo controlled clinical trials. They have shown a mild efficacy in mild to moderate AD. Memantine, a NMDA antagonist is the only drug that has demonstrated mild efficacy in moderate to severe AD in controlled clinical trial. Clinical trials surveying the efficacy of active and passive immunization against B amyloid protoin has halted due to serious adverse events. Studies of inducing neurogenesis in brain of AD patients are preliminary. Antipsychotics have shown efficacy for controlling BD of AD patients but they are associated with adverse events. Except for carbamazepine, there is not enough evidence for other anticanvulsants to be effective for behavioral disturbances of AD patients. A controlled clinical trial and some open studies have shown the efficacy of citalopram for BD. Further studies are needed to confirm the efficacy of other medications like trazadon, buspiron and beta blockers for BD. Conclusion: Cholinesterase inhibitors have demonstrated disappointing results. Memantine is only mildly effective for cognitive deficit. To date, no amyloid-modifying therapy has yet been successful in phase 3 clinical trials
Bell, Andrew S.; Huijben, Silvie; Paaijmans, Krijn P.; Sim, Derek G.; Chan, Brian H. K.; Nelson, William A.; Read, Andrew F.
The evolution of drug resistant Plasmodium parasites is a major challenge to effective malaria control. In theory, competitive interactions between sensitive parasites and resistant parasites within infections are a major determinant of the rate at which parasite evolution undermines drug efficacy. Competitive suppression of resistant parasites in untreated hosts slows the spread of resistance; competitive release following treatment enhances it. Here we report that for the murine model Plasm...
Gemal, Andre; Keravec, Joel; Menezes, Alexandre; Trajman, Anete
Despite the existence of effective treatment, tuberculosis is still a global public health issue. The World Health Organization recommends a six-month four-drug regimen in fixed-dose combination formulation to treat drug sensitive tuberculosis, and long course regimens with several second-line drugs to treat multi-drug resistant tuberculosis. To achieve the projected tuberculosis elimination goal by 2050, it will be essential to ensure a non-interrupted supply of quality-assured tuberculosis drugs. However, quality and affordable tuberculosis drug supply is still a significant challenge for National Tuberculosis Programs. Quality drug production requires a combination of complex steps. The first challenge is to guarantee the quality of tuberculosis active pharmaceutical ingredients, then ensure an adequate manufacturing process, according to international standards, to guarantee final product's safety, efficacy and quality. Good practices for storage, transport, distribution and quality control procedures must follow. In contrast to other high-burden countries, Brazil produces tuberculosis drugs through a strong network of public sector drug manufacturers regulated by a World Health Organization-certified national sanitary authority. The installed capacity for production surpasses the 71,000 needed treatments in the country. However, in order to be prepared to act as a global supplier, important bottlenecks are to be overcome. This article presents an in-depth analysis of the current status of production of tuberculosis drugs in Brazil and the bottlenecks and opportunities for the country to sustain national demand and play a role as a potential global supplier. Raw material and drug production, quality control, international certification and pre-qualification, political commitment and regulatory aspects are discussed, as well recommendations for tackling these bottlenecks. This discussion becomes more important as new drugs and regimens to treat tuberculosis are
... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Residential Drug Abuse Treatment Program... INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Abuse Treatment Program § 550.53 Residential Drug Abuse Treatment... components: (1) Unit-based component. Inmates must complete a course of activities provided by drug abuse...
Carfora, Anna; Cassandro, Paola; Feola, Alessandro; La Sala, Francesco; Petrella, Raffaella; Borriello, Renata
Different immunotherapeutic approaches are in the pipeline for the treatment of drug dependence. "Drug vaccines" aim to induce the immune system to produce antibodies that bind to drugs and prevent them from inducing rewarding effects in the brain. Drugs of abuse currently being tested using these new approaches are opioids, nicotine, cocaine, and methamphetamine. In human clinical trials, "cocaine and nicotine vaccines" have been shown to induce sufficient antibody levels while producing few side effects. Studies in humans, determining how these vaccines interact in combination with their target drug, are underway. However, although vaccines can become a reasonable treatment option for drugs of abuse, there are several disadvantages that must be considered. These include i) great individual variability in the formation of antibodies, ii) the lack of protection against a structurally dissimilar drug that produces the same effects as the drug of choice, and iii) the lack of an effect on the drug desire that may predispose an addict to relapse. In addition, a comprehensive overview of several crucial ethical issues has not yet been widely discussed in order to have not only a biological approach to immunotherapy of addiction. Overall, immunotherapy offers a range of possible treatment options: the pharmacological treatment of addiction, the treatment of overdoses, the prevention of toxicity to the brain or the heart, and the protection of the fetus during pregnancy. So far, the results obtained from a small-scale experiment using vaccines against cocaine and nicotine suggest that a number of important technical challenges still need to be overcome before such vaccines can be approved for clinical use.
Bhagavathula, Akshaya Srikanth; Elnour, Asim Ahmed; Shehab, Abdulla
bullet against malaria. Future studies should focus on effective single-dose molecules that can act against all stages of malaria in order to prevent transmission. Newer medicines have also raised concerns in terms of efficacy and safety. Overall, more evidence is needed to effectively reduce the current malaria burden. Treatment strategies that target the blood stage with transmission-blocking properties are needed to prevent future drug resistance.
I. O. Shchederkina
Full Text Available Among drug-resistant epilepsies, epileptic syndromes, characterized by combination of several types of seizures, are considered to be the most difficult in terms of treatment. Lennox–Gastaut syndrome is one of them. It manifests with polymorphic seizures (tonic axial, myatonic, atypical absence seizures, status epilepticus of minor motor seizures, myoclonic, generalized convulsive, and focal seizures. This is a heterogeneous disease, represented by a complex of clinical and electroencephalographic manifestations with various etiology. Current review is devoted to a novel antiepileptic drug rufinamide, which has a new mechanism of action. The drug has been registered in Russia in 2015. The authors also describe their own experience of rufinamide usage in the treatment of drug-resistant focal epilepsy as a part of multicomponent therapy for polymorphic seizures. One patient achieved clinical remission for 16 months; the second one had more than 50 % decrease in seizures frequency with a remission of drop-attacks.
Hochlowski, Jill E; Pan, Jeffrey Y; Searle, Philip A; Buck, Wayne R; Spanton, Stephen G
Experiments were performed to demonstrate the potential of counter-current chromatography (CCC) for the isolation of drugs and their metabolites from biological matrices relevant to the metabolism studies of pharmaceutical research. Examples of typical drugs are spiked into biological media ex vivo to provide test samples for analysis. A mass spectrometer hyphenated to a CCC allows for the detection of small molecule drugs within the matrix through selected ion monitoring, and fraction collection can provide material for further structural elucidation by NMR.
Paragliola, Rosa Maria; Prete, Alessandro; Kaplan, Peter W; Corsello, Salvatore Maria; Salvatori, Roberto
Evidence suggests that there may be drug interactions between antiepileptic drugs and hormonal therapies, which can present a challenge to endocrinologists dealing with patients who have both hypopituitarism and neurological diseases. Data are scarce for this subgroup of patients; however, data for the interaction of antiepileptic drugs with the pituitary axis have shown that chronic use of many antiepileptic drugs, such as carbamazepine, oxcarbazepine, and topiramate, enhances hepatic cytochrome P450 3A4 (CYP3A4) activity, and can decrease serum concentrations of sex hormones. Other antiepileptic drugs increase sex hormone-binding globulin, which reduces the bioactivity of testosterone and estradiol. Additionally, the combined oestrogen-progestagen contraceptive pill might decrease lamotrigine concentrations, which could worsen seizure control. Moreover, sex hormones and their metabolites can directly act on neuronal excitability, acting as neurosteroids. Because carbamazepine and oxcarbazepine can enhance the sensitivity of renal tubules, a reduction in desmopressin dose might be necessary in patients with central diabetes insipidus. Although the effects of antiepileptic drugs in central hypothyroidism have not yet been studied, substantial evidence indicates that several antiepileptic drugs can increase thyroid hormone metabolism. However, although it is reasonable to expect a need for a thyroxine dose increase with some antiepileptic drugs, the effect of excessive thyroxine in lowering seizure threshold should also be considered. There are no reports of significant interactions between antiepileptic drugs and the efficacy of human growth hormone therapy, and few data are available for the effects of second-generation antiepileptic drugs on hypopituitarism treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.
Arnold, Lesley M; Clauw, Daniel J
The current diagnostic and treatment pathway for patients with fibromyalgia (FM) is lengthy, complex, and characterized by multiple physician visits with an average 2-year wait until diagnosis. It is clear that effective identification and appropriate treatment of FM remain a challenge in current clinical practice. Ideally, FM management involves a multidisciplinary approach with the preferable patient pathway originating in primary care but supported by a range of health care providers, including referral to specialist care when necessary. After the publication of individual clinical studies, high-quality reviews, and meta-analyses, recently published FM treatment guidelines have transitioned from an expert consensus to an evidence-based approach. Evidence-based guidelines provide a framework for ensuring early diagnosis and timely adoption of appropriate treatment. However, for successful outcomes, FM treatments must adopt a more holistic approach, which addresses more than just pain. Impact on the associated symptoms of fatigue and cognitive problems, sleep and mood disturbances, and lowered functional status are also important in judging the success of FM therapy. Recently published guidelines recommend the adoption of a symptom-based approach to guide pharmacologic treatment. Emerging treatment options for FM may be best differentiated on the basis of their effect on comorbid symptoms that are often associated with pain (e.g. sleep disturbance, mood, fatigue). The current review discusses the most recently published Canadian guidelines and the implications of the recent European League Against Rheumatism (EULAR) recommendations, with a focus on the challenges of implementing these guidelines in current clinical practice.
Ridwelski, K; Meyer, F
Palliative treatment is often the only remaining option in the management of pancreatic carcinoma, but its efficacy is poor due to low tumor sensitivity and inadequate treatment protocols. There are several options of palliative treatment with antitumor or supportive intention. Classical end points of palliative treatment are survival, tumor response, and quality of life. A decade ago, palliative chemotherapy consisted mainly of 5-fluorouracil as the standard agent in combination with either other agents and/or radiotherapy. Only the new antineoplastic drug gemcitabine, which was introduced simultaneously with the definition of novel end points of chemotherapy such as clinical benefit, allowed to achieve some progress. However, while gemcitabine monotherapy appeared to be superior to 5-fluorouracil and improved important parameters of quality of life, it could not provide a significant improvement of survival. A novel concept, therefore, is to improve this beneficial cytostatic response in pancreatic carcinoma using a gemcitabine-based protocol by combining it with antineoplastic drugs such as taxanes or platin analogs. This strategy may have the potential to improve the outcome in palliative chemotherapy of pancreatic carcinoma patients with advanced tumor growth or metastases. Best supportive care in pancreatic cancer consists of the treatment of symptoms, such as pain, jaundice, duodenal obstruction, weight loss, exocrine pancreatic insufficiency, and tumor-associated depression. Copyright 2001 S. Karger AG, Basel
Paulus, Martin P; Stewart, Jennifer L; Haase, Lori
There is emerging evidence that individuals with drug addiction have dysfunctions in brain systems that are important for interoceptive processing, which include, among others, the insular and the anterior cingulate cortices. These individuals may not be expending sufficient neural resources to process perturbations of the interoceptive state but may exert over-activation of these systems when processing drug-related stimuli. As a consequence, insufficient detection and processing of interoceptive state changes may result in inadequate anticipation and preparation to adapt to environmental challenges, e.g., adapt to abstinence in the presence of withdrawal symptoms. Here, we integrate interoceptive dysfunction in drug-addicted individuals, with the neural basis for meditation and exercise to develop a heuristic to target the interoceptive system as potential treatments for drug addiction. First, it is suggested that mindfulness-based approaches can modulate both interoceptive function and insular activation patterns. Second, there is an emerging literature showing that the regulation of physical exercise in the brain involves the insula and anterior cingulate cortex and that intense physical exercise is associated with a insula changes that may provide a window to attenuate the increased interoceptive response to drug-related stimuli. It is concluded that the conceptual framework of interoceptive dysfunctions in drug addiction and the experimental findings in meditation and exercise provide a useful approach to develop new interventions for drug addiction.
Martin P Paulus
Full Text Available There is emerging evidence that individuals with drug addiction have dysfunctions in brain systems that are important for interoceptive processing, which include, among others, the insular and the anterior cingulate cortices. These individuals may not be expending sufficient neural resources to process perturbations of the interoceptive state but may exert over-activation of these systems when processing drug-related stimuli. As a consequence, insufficient detection and processing of interoceptive state changes may result in inadequate anticipation and preparation to adapt to environmental challenges, e.g. adapt to abstinence in the presence of withdrawal symptoms. Here, we integrate interoceptive dysfunction in drug-addicted individuals, with the neural basis for meditation and exercise to develop a heuristic to target the interoceptive system as potential treatments for drug addiction. First, it is suggested that mindfulness-based approaches can modulate both interoceptive function and insular activation patterns. Second, there is an emerging literature that the regulation of physical exercise in the brain involves the insula and anterior cingulate cortex and that intense physical exercise is associated with a state-dependent activation difference in the insula that may provide a window to attenuate the increased interoceptive response drug related stimuli. It is concluded that the conceptual framework of interoceptive dysfunctions in drug addiction and the experimental findings in meditation and exercise provide a useful approach to develop new interventions for drug addiction.
Poetschke, Julian; Gauglitz, Gerd G
Scarring is the consequence of surgery, trauma or different skin diseases. Apart from fresh, immature scars,that transform into mature scars over the course of would healing and that do not require further treatment,linear hypertrophic scars, widespread hypertrophic scars, keloids and atrophic scars exist. Symptoms like pruritusand pain, stigmatization as well as functional and aesthetic impairments that are very disturbing for the affected patients can bethe basis for the desire for treatment. Today, a multitude of options for the treatment and prevention of scars exists. Topical agents based on silicone or onion extract, intralesional injections of cristalline glucocorticoids (oftentimes in combinationwith cryotherapy) or 5-Fluorouracil as well as ablative and nonablative laser treatment are used. Current guidelines summarize the multitude of available treatment options and the currently available datafor the treating physicians, allowing them to make clear therapy recommendations for every single scar type. Relieving patients of their discomfort and doing their aesthetic demands justice is thus possible. Apart from scar prevention becoming more and more important, the increased use of modernlaser treatment options constitutes a key point in clinical scar treatment. At the same time the attention is turned to evaluating current therapeutic options with the help of contemporary study designs so as to graduallyimprove the level of evidence in scar treatment. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.
Abida*, Md. Tauqir Alam, Mohd. Imran, Said A.H. El-Feky, Mohamed A.M. Hagga
Fibromyalgia is a disorder, which is characterized by widespread musculoskeletal pain accompanied by fatigue, memory, mood, and sleep issues. Scientists believe that this condition may be due to injury, emotional distress, or viruses that change the way the brain perceives pain, but the exact cause is unclear. Generally, fibromyalgia is treated with antidepressants, pain relievers, and Anti-seizure drugs. There is not much specific treatment available for the treatment and management of fibro...
nucleotides with specific enzymes (67). Some commonly used purine analogs 20 6- Mercaptopurine 6-Thioguanine SH SH Ni N N N NH 2 NkN N H H Azathiopine CH3...Chemotherapeutic Drugs. 21 include: 6- Mercaptopurine , which is used for the treatment of acute leukemias (Fig 4). 6-Thioguanine, which is also used in the treatment... degradation of nucleic acids or nucleotides. In contrast, Leihmania. spp. rely primarily on the salvage pathways for their source of nucleotides. They
Full Text Available Abstract Alzheimer’s disease (AD is a neurodegenerative disorder that impairs mainly the memory and cognitive function in elderly. Extracellular beta amyloid deposition and intracellular tau hyperphosphorylation are the two pathological events that are thought to cause neuronal dysfunction in AD. Since the detailed mechanisms that underlie the pathogenesis of AD are still not clear, the current treatments are those drugs that can alleviate the symptoms of AD patients. Recent studies have indicated that these symptom-reliving drugs also have the ability of regulating amyloid precursor protein processing and tau phosphorylation. Thus the pharmacological mechanism of these drugs may be too simply-evaluated. This review summarizes the current status of AD therapy and some potential preclinical considerations that target beta amyloid and tau protein are also discussed.
Mattson, Curtis; Powers, Bradley; Halfaker, Dale; Akeson, Steven; Ben-Porath, Yossef
We examined the ability of the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008) substantive scales to predict Drug Court treatment completion in a sample of individuals identified as being at risk for failure to complete the program. Higher scores on MMPI-2-RF scales…
We have published "Guideline for the Treatment of Graves' Disease with Antithyroid Drug in Japan 2006" in the middle of May from the Japan Thyroid Association. The background, working process, composition, aim and significance of this guideline are described. The most remarkable feature of this guideline is "evidence based".
Compares a new approach to treatment using traditional social work. Reports on the therapeutic regimen and Results/Kinesiology (RK), which addresses body-mind control, brain hemispheric integration, energy balancing, and stress elimination. Examination of 40 women addicted to alcohol and/or drugs indicated that RK helped with anxiety,…
Den Boer, JA; Bosker, FJ; Slaap, BR
Serotonergic dysfunction has been implicated in the aetiology of several psychiatric conditions, including depressive and anxiety disorders. Much of the evidence for the role of serotonin (5-HT) in these disorders comes from treatment studies with serotonergic drugs, including selective serotonin
Due diligence in the process of provision of healthcare services refers, among other elements, to the application of pharmacological therapy at a time which offers the greatest chance for a successful outcome of treatment, i.e. for achieving the optimum expected effect understood as an improvement in the patient's health, reduction of health risks or elimination of the disease. However, due diligence may also refer to actions aimed at ensuring that neither the patient nor the healthcare payer is required to incur unreasonable costs in the process of treatment. The validity of that statement stems not only from normative acts but also from ethical standards laid down in the Medical Code of Ethics (Article 57 section 2). It often happens that the provision of optimal treatment calls for deviations from the formal provisions included in Summary Product Characteristics (SPCs), and the application of drugs that are bioequivalent to reference drugs, which translates into a significant reduction of costs. The present study addresses the problem of acceptability of a specific form of drug substitution consisting in the replacement of a reference drug with a generic drug. Also explored are legal aspects associated with the possibility of therapy based on “off-label use”. The study reviews normative acts existing in the Polish and EU legislation. It also provides a clear definition of orphan drug, which has made it possible to make a distinction and investigate mutual relations between the concepts of brand-name (reference) drug, orphan drug and generic drug. PMID:24592133
Zajdel, Justyna; Zajdel, Radosław
Due diligence in the process of provision of healthcare services refers, among other elements, to the application of pharmacological therapy at a time which offers the greatest chance for a successful outcome of treatment, i.e. for achieving the optimum expected effect understood as an improvement in the patient's health, reduction of health risks or elimination of the disease. However, due diligence may also refer to actions aimed at ensuring that neither the patient nor the healthcare payer is required to incur unreasonable costs in the process of treatment. The validity of that statement stems not only from normative acts but also from ethical standards laid down in the Medical Code of Ethics (Article 57 section 2). It often happens that the provision of optimal treatment calls for deviations from the formal provisions included in Summary Product Characteristics (SPCs), and the application of drugs that are bioequivalent to reference drugs, which translates into a significant reduction of costs. The present study addresses the problem of acceptability of a specific form of drug substitution consisting in the replacement of a reference drug with a generic drug. Also explored are legal aspects associated with the possibility of therapy based on "off-label use". The study reviews normative acts existing in the Polish and EU legislation. It also provides a clear definition of orphan drug, which has made it possible to make a distinction and investigate mutual relations between the concepts of brand-name (reference) drug, orphan drug and generic drug.
Chakera, Ali J; Pearce, Simon HS; Vaidya, Bijay
Primary hypothyroidism is the most common endocrine disease. Although the diagnosis and treatment of hypothyroidism is often considered simple, there are large numbers of people with this condition who are suboptimally treated. Even in those people with hypothyroidism who are biochemically euthyroid on levothyroxine replacement there is a significant proportion who report poorer quality of life. This review explores the historical and current treatment options for hypothyroidism, reasons for and potential solutions to suboptimal treatment, and future possibilities in the treatment of hypothyroidism. PMID:22291465
Paksoy, Melih; Sekmen, Ümit
Groin pain is an important clinical entity that may affect a sportsman's active sports life. Sportsman's hernia is a chronic low abdominal and groin pain syndrome. Open and laparoscopic surgical treatment may be chosen in case of conservative treatment failure. Studies on sportsman's hernia, which is a challenging situation in both diagnosis and treatment, are ongoing in many centers. We reviewed the treatment results of 37 patients diagnosed and treated as sportsman's hernia at our hospital between 2011-2014, in light of current literature.
Immunotherapy has a great potential of becoming a new therapeutic strategy in the treatment of addiction to psychoactive drugs. It may be used to treat addiction but also to prevent neurotoxic complications of drug overdose. In preclinical studies two immunological methods have been tested; active immunization, which relies on the administration of vaccines and passive immunization, which relies on the administration of monoclonal antibodies. Until now researchers have succeeded in developing vaccines and/or antibodies against addiction to heroin, cocaine, methamphetamine, nicotine and phencyclidine. Their effectiveness has been confirmed in preclinical studies. At present, clinical studies are being conducted for vaccines against nicotine and cocaine and also anti-methamphetamine monoclonal antibody. These preclinical and clinical studies suggest that immunotherapy may be useful in the treatment of addiction and drug overdose. However, there are a few problems to be solved. One of them is controlling the level of antibodies due to variability between subjects. But even obtaining a suitable antibody titer does not guarantee the effectiveness of the vaccine. Additionally, there is a risk of intentional or unintentional overdose. As vaccines prevent passing of drugs through the blood/brain barrier and thereby prevent their positive reinforcement, some addicted patients may erroneously seek higher doses of psychoactive substances to get "high". Consequently, vaccination should be targeted at persons who have a strong motivation to free themselves from drug dependency. It seems that immunotherapy may be an opportunity for effective treatment of drug addiction if directed to adequate candidates for treatment. For other addicts, immunotherapy may be a very important element supporting psycho- and pharmacotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.
Sundström, Mira; Pelander, Anna; Simojoki, Kaarlo; Ojanperä, Ilkka
The most severe consequences of drug abuse include infectious diseases, overdoses, and drug-related deaths. As the range of toxicologically relevant compounds is continually changing due to the emergence of new psychoactive substances (NPS), laboratories are encountering analytical challenges. Current immunoassays are insufficient for determining the whole range of the drugs abused, and a broad-spectrum screening method is therefore needed. Here, the patterns of drug abuse in two groups of drug users were studied from urine samples using a comprehensive screening method based on high-resolution time-of-flight mass spectrometry. The two groups comprised drug abusers undergoing opioid maintenance treatment (OMT) or drug withdrawal therapy and routinely visiting a rehabilitation clinic, and drug abusers with irregular attendance at a harm reduction unit (HRU) and suspected of potential NPS abuse. Polydrug abuse was observed in both groups, but was more pronounced among the HRU subjects with a mean number of concurrent drugs per sample of 3.9, whereas among the regularly treated subjects the corresponding number was 2.1. NPS and pregabalin were more frequent among HRU subjects, and their abuse was always related to drug co-use. The most common drug combination for an HRU subject included amphetamine, cannabis, buprenorphine, benzodiazepine, and alpha-pyrrolidinovalerophenone. A typical set of drugs for treated subjects was buprenorphine, benzodiazepine, and occasionally amphetamine. Abuse of several concurrent drugs poses a higher risk of drug intoxication and a threat of premature termination of OMT. Since the subjects attending treatment used fewer concurrent drugs, this treatment could be valuable in reducing polydrug abuse. Copyright © 2015 John Wiley & Sons, Ltd.
Full Text Available Background. The aim of the study was to explore the epidemiology of drug abuse treatment in South Africa. Methods. Treatment demand statistics were analysed from South African National Council on Alcoholism and Drug Dependence and the South African Community Epidemiology Network on Drug Use records, and a rapid situation assessment was conducted. Twenty-one key informant interviews were conducted in all 9 provinces among provincial substance abuse co-ordinators, and one manager per treatment centre from a sample of treatment centres. Three focus groups were conducted and 46 self-administered questionnaires were distributed among inpatients at 2 selected treatment centres in Free State and North West provinces. Qualitative data were analysed using grounded theory, and quantitative data analysed using SPSS. Results. Treatment records show that the most frequent substance of abuse was alcohol (51%, followed by cannabis (21%, crack/cocaine (9.6%, heroin/opiates (7.9%, methamphetamine (Tik (4.5%, prescription/over-the-counter drugs (2.0%, and cannabis/mandrax (1.7%. More substance abusers were male, of lower education, white or black, than were female, more highly educated, coloured and Indian/Asian. Key informant interviews showed that females are the ‘hidden’ substance abusers and tend not to be identified in research statistics and at treatment centres. Poverty, unemployment, lack of recreational facilities, being surrounded by substance abusers, and long work shifts were also mentioned as factors contributing to substance abuse. The age of initiation of substance abuse using non-drugs such as glue was 9 years old, alcohol 10 - 12 years old, dagga 11 - 12 years old, poly-drug use (alcohol, tobacco and dagga 14 years old, and harder drugs such as cocaine and heroin at 16 - 17 years old, as reported by key informants. Family care and support, improved socio-economic conditions and increased law enforcement would help to discourage substance
Linnert, Mette; Iversen, Helle Klingenberg; Gehl, Julie
BACKGROUND: Due to the advanced oncological treatments of cancer, an overall increase in cancer incidence, and better diagnostic tools, the incidence of brain metastases is on the rise. This review addresses the current treatment options for patients with multiple brain metastases, presenting...... of the chemotherapeutic drug bleomycin by 300 times. Preclinical data are promising and the first patient has been treated in an ongoing clinical trial for patients with brain metastases. Perspectives for ECT in the brain include treatment of primary and secondary brain tumors as well as soft tissue metastases elsewhere....
Malav Suchin Trivedi
Full Text Available Alcohol and other drugs of abuse, including psychostimulants and opioids, can induce epigenetic changes: a contributing factor for drug addiction, tolerance and associated withdrawal symptoms. DNA methylation is the major epigenetic mechanism and it is one of more than 200 methylation reactions supported by methyl donor S-adenosylmethionine (SAM. The levels of SAM are controlled by cellular redox status via the folate and vitamin B12-dependent enzyme methionine synthase (MS, for example; under oxidative conditions MS is inhibited, diverting its substrate homocysteine (HCY to the transsulfuration pathway. Alcohol, dopamine and morphine, can alter intracellular levels of glutathione (GSH-based cellular redox status, subsequently affecting S-adenosylmethionine (SAM levels and DNA methylation status. In this discussion, we compile this and other existing evidence in a coherent manner to present a novel hypothesis implicating the involvement of redox-based epigenetic changes in drug addiction. Next, we also discuss how gene priming phenomenon can contribute to maintenance of redox and methylation status homeostasis under various stimuli including drugs of abuse. Lastly, based on our hypothesis and some preliminary evidence, we discuss a mechanistic explanation for use of metabolic interventions / redox-replenishers as symptomatic treatment of alcohol addiction and associated withdrawal symptoms. Hence, the current review article strengthens the hypothesis that neuronal metabolism has a critical bidirectional coupling with epigenetic changes in drug addiction and we support this claim via exemplifying the link between redox-based metabolic changes and resultant epigenetic consequences under the effect of drugs of abuse.
Ulfvarson, Johanna; Bardage, Carola; Wredling, Regina A-M; von Bahr, Christer; Adami, Johanna
This study was to explore concordance with drugs prescribed and the patient's self-reported drug consumption, in relation to the older patient's perceived care and information given. Lack of adherence to prescriptions may lead to therapeutic failure with risks for relapse, unnecessary suffering and increased costs. A cross-sectional study with structured interviews of 200 patients who had recently been treated in a medical ward. Patients' medical records were studied to obtain information on their current use of drugs. The data were analyzed by logistic regression, adherence being the dependent response variable. The mean age of the study group was 79 years. The number of drugs reported in the medical chart ranged from one to 17 with a mean of 6.9. The patients reported a drug consumption ranging from 0 to 24 with a mean of 7.3. When comparing the interview results with the information in the medical charts, 30% of the patients showed adherence. An association was found between adherence and self-reported health status. Patients in the non-adherent group reported a higher consumption of drugs. Patients felt that the opportunity to ask questions of either the responsible physicians or of the nurses was influential in decreasing risk. In this study, the patient's total drug consumption was considered. The study showed a large discrepancy between the drugs stated in the medical chart and patient's self-reported drug consumption. The study failed to show that perceived information or educational level had an impact on the results but implicate that the quality of information influences adherence. It is of importance to recognize patients at risk for non-adherence. Decreased health status and many drugs are the main risk factors for patients being non-adherent, and should be recognized as such.
Nielsen, Lars Hougaard; Løkkegaard, Ellen; Andreasen, Anne Helms
of this misclassification for analysing the risk of breast cancer. MATERIALS AND METHODS: Prescription data were obtained from Danish Registry of Medicinal Products Statistics and we applied various methods to approximate treatment episodes. We analysed the duration of HT episodes to study the ability to identify......PURPOSE: Many studies which investigate the effect of drugs categorize the exposure variable into never, current, and previous use of the study drug. When prescription registries are used to make this categorization, the exposure variable possibly gets misclassified since the registries do...... not carry any information on the time of discontinuation of treatment.In this study, we investigated the amount of misclassification of exposure (never, current, previous use) to hormone therapy (HT) when the exposure variable was based on prescription data. Furthermore, we evaluated the significance...
Ciato, Denis; Mumbach, Aizhar G; Paez-Pereda, Marcelo; Stalla, Günter K
Cushing's disease (CD) is caused by a corticotroph adenoma of the pituitary gland that secretes excess adrenocorticotropic hormone (ACTH) causing increased morbidity and mortality. Surgery is the treatment of choice, but is not always successful. Alternatives include radiotherapy, adrenal surgery, and pharmaceutical therapy. The latter is increasingly gaining momentum due to the recent development of compounds that reduce hypercortisolaemia or its symptoms, acting through different mechanisms. Areas covered: In this article, the authors provide a complete overview of the treatment options for Cushing´s disease, including adrenal-directed, tumor-targeted, and peripheral therapies that are currently used or in development, and discuss their potential advantages and limitations. Expert opinion: Considering the lack of long-term remission in up to half of the patients after surgery, and the delayed response to radiotherapy along with potential side effects, there is a strong need for an effective pharmaceutical treatment. Pasireotide, mifepristone, ketoconazole and metyrapone have been approved by regulatory authorities but their use remains limited due to considerable costs and side effects. Research in this field has focused recently on the improvement of pre-existing drugs and the development of safe new ones. However, few approaches aim at targeting the source of the disease, the ACTH-secreting adenoma.
Cheng, Z; Dai, M M; Cao, X B
Methadone maintenance treatment (MMT) greatly contributed to the successful outcomes of prevention and control on both AIDS and drug abuse in China. However, the features on drug abuse changed in the past decades, and the prevalence of new psychoactive substances abuse potentially somehow offset the achievement of MMT. This paper concised the information on research and surveys of this issue that targeting on the current situation, characteristics, related factors and relevant public health problem on new psychoactive substances abuse, among patients who have been on MMT, in China.
Full Text Available Renato Mantegazza, Silvia Bonanno, Giorgia Camera, Carlo AntozziDepartment of Neuromuscular Diseases and Neuroimmunology, Fondazione Istituto Neurologico Carlo Besta, Milan, ItalyAbstract: Myasthenia gravis (MG is an autoimmmune disease in which autoantibodies to different antigens of the neuromuscular junction cause the typical weakness and fatigability. Treatment includes anticholinesterase drugs, immunosuppression, immunomodulation, and thymectomy. The autoimmune response is maintained under control by corticosteroids frequently associated with immunosuppressive drugs, with improvement in the majority of patients. In case of acute exacerbations with bulbar symptoms or repeated relapses, modulation of autoantibody activity by plasmapheresis or intravenous immunoglobulins provides rapid improvement. Recently, techniques removing only circulating immunoglobulins have been developed for the chronic management of treatment-resistant patients. The rationale for thymectomy relies on the central role of the thymus. Despite the lack of controlled studies, thymectomy is recommended as an option to improve the clinical outcome or promote complete remission. New videothoracoscopic techniques have been developed to offer the maximal surgical approach with the minimal invasiveness and hence patient tolerability. The use of biological drugs such as anti-CD20 antibodies is still limited but promising. Studies performed in the animal model of MG demonstrated that several more selective or antigen-specific approaches, ranging from mucosal tolerization to inhibition of complement activity or cellular therapy, might be feasible. Investigation of the transfer of these therapeutic approaches to the human disease will be the challenge for the future.Keywords: myasthenia gravis, therapy, immunosuppression, thymectomy, plasmapheresis
Mantegazza, Renato; Bonanno, Silvia; Camera, Giorgia; Antozzi, Carlo
Myasthenia gravis (MG) is an autoimmmune disease in which autoantibodies to different antigens of the neuromuscular junction cause the typical weakness and fatigability. Treatment includes anticholinesterase drugs, immunosuppression, immunomodulation, and thymectomy. The autoimmune response is maintained under control by corticosteroids frequently associated with immunosuppressive drugs, with improvement in the majority of patients. In case of acute exacerbations with bulbar symptoms or repeated relapses, modulation of autoantibody activity by plasmapheresis or intravenous immunoglobulins provides rapid improvement. Recently, techniques removing only circulating immunoglobulins have been developed for the chronic management of treatment-resistant patients. The rationale for thymectomy relies on the central role of the thymus. Despite the lack of controlled studies, thymectomy is recommended as an option to improve the clinical outcome or promote complete remission. New videothoracoscopic techniques have been developed to offer the maximal surgical approach with the minimal invasiveness and hence patient tolerability. The use of biological drugs such as anti-CD20 antibodies is still limited but promising. Studies performed in the animal model of MG demonstrated that several more selective or antigen-specific approaches, ranging from mucosal tolerization to inhibition of complement activity or cellular therapy, might be feasible. Investigation of the transfer of these therapeutic approaches to the human disease will be the challenge for the future. PMID:21552317
Nutt, David J
Anxiety disorders are common and often disabling. They fall into five main categories: panic disorder, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder and posttraumatic stress disorder, each of which have characteristic symptoms and cognitions. All anxiety disorders respond to drugs and psychological treatments. This review will focus on drug treatments. Recent research has emphasized the value of antidepressants especially the selective serotonin reuptake inhibitors, benzodiazepines, and related sedative-like compounds. The common co-existence of depression with all of the anxiety disorders means that the selective serotonin reuptake inhibitors are now generally considered to be the first-line treatments but the benzodiazepines have some utility especially in promoting sleep and working acutely to reduce extreme distress.
Evidence supporting the efficacy of beta blockers in anxiety is reviewed. Propranolol and oxprenolol are the most clearly established in efficacy. A placebo-controlled trial is described, in which propranolol and atenolol were both effective in the symptomatic treatment of generalized anxiety in patients who had been referred by their family doctors for specialist treatment. If initial psychological treatment for chronic anxiety is ineffective, and a drug is considered necessary, then a beta blocker or an antidepressant should be considered as first choice in preference to a benzodiazepine.
Andrew W. Campbell
Full Text Available Onychomycosis is a common nail disease responsible for approximately 50% of diseases of the nail. It occurs more in the elderly, though several cases have been reported among children. Several factors influence, such as climate, geography, and migration. The two dermatophytes most commonly implicated in onychomycosis are Trichophyton rubrum and T. mentagrophytes, accounting for more than 90% of onychomycoses. Nonetheless, several other toxigenic molds have been implicated. For convenience, onychomycosis is divided into four major clinical presentations: distal subungal, which is the most common form of the disease; proximal subungal, which is the most common form found in patients with human immunodeficiency virus infection; superficial; and total dystrophic onychomycosis. Epidemiology of onychomycosis in adults and children is evaluated and the most common clinical symptoms addressed. Although the risk factors are discussed, the multifactorial nature of onychomycosis makes this inexhaustible. The diagnosis and treatments are difficult and the choice of appropriate antifungal drugs complex and require the knowledge of the chemical structures of the metabolites of the molds that cause onychomycosis and their interaction with the antifungal drugs. This is true because most of the antifungal drugs are derived from mold/fungal metabolism. Treatment with griseofulvin and amphotericin is displaced by the use of newer drugs from azole compounds, pyrimidines, and allylamines derivatives. Amorolfine, itraconazole, and ciclopirox nail lacquer solution 8 have gained support globally, but the side effects, drug resistance, and persistence of the disease are still a serious concern to the patients, just as economics and quality of life. Hence, the search for safer and more efficacious drug treatments are continuing.
Laís Bastos da Fonseca
Full Text Available Schistosomiasis is a parasitic disease that, according to the World Health Organization, constitutes a major public health problem associated with severe morbidity, mostly children in preschool age. The administration of drugs in children always constitutes a difficult task, especially when formulations are not developed specifically for pediatric use, when high doses of drug are required and the drug has a bitter taste, as in the case of praziquantel. Polymer nanoparticles are promising systems for development of encapsulated drugs with low water solubility and bitter taste, due to the good physical and chemical stability, adequate biocompatibility and simple manufacturing processes. Moreover, they can enhance the bioavailabili-ty and reduce variability of treatment among patients. Poly (methyl methacrylate doped with praziquantel was produced through a miniemulsion polymerization pro-cess to compose a pediatric pharmaceutical suspension. Nanoparticles were cha-racterized in terms of physico-chemical properties, toxicological properties and biological activity in mice, being concluded that obtained results were satisfactory. The results were encapsulation rate around 90%, absence of chemical interaction drug - polymer and the presence of biological activity. A collaborative approach was used for this development, involving national partnerships and independent funding mechanisms, a powerful pathway for development of drugs for neglected diseases.
Full Text Available The rapid evolution of influenza virus makes antiviral drugs less effective, which is considered to be a major bottleneck in antiviral therapy. The key proteins in the host cells, which are related with the replication cycle of influenza virus, are regarded as potential drug targets due to their distinct advantage of lack of evolution and drug resistance. Cdc2-like kinase 1 (CLK1 in the host cells is responsible for alternative splicing of the M2 gene of influenza virus during influenza infection and replication. In this study, we carried out baculovirus-mediated expression and purification of CLK1 and established a reliable screening assay for CLK1 inhibitors. After a virtual screening of CLK1 inhibitors was performed, the activities of the selected compounds were evaluated. Finally, several compounds with strong inhibitory activity against CLK1 were discovered and their in vitro anti-influenza virus activities were validated using a cytopathic effect (CPE reduction assay. The assay results showed that clypearin, corilagin, and pinosylvine were the most potential anti-influenza virus compounds as CLK1 inhibitors among the compounds tested. These findings will provide important information for new drug design and development in influenza treatment, and CLK1 may be a potent drug target for anti-influenza drug screening and discovery.
Raposo, Inês; Torres, Tiago
Palmoplantar psoriasis and palmoplantar pustulosis are chronic skin diseases with a large impact on patient quality of life. They are frequently refractory to treatment, being generally described as a therapeutic challenge. This article aims to review the definitions of palmoplantar psoriasis and palmoplantar pustulosis, highlighting the similarities and differences in terms of epidemiology, clinical presentation, genetics, histopathology, and pathogenesis, as well as treatment options for both entities. Classical management of mild to moderate palmoplantar pustulosis and palmoplantar psoriasis relies on use of potent topical corticosteroids, phototherapy, and/or acitretin. Nevertheless, these drugs have proven to be insufficient in long-term control of extensive disease. Biologic therapy-namely, anti-interleukin-17 agents and phosphodiesterase type 4 inhibitors-has recently shown promising results in the treatment of palmoplantar psoriasis. Knowledge of the pathophysiologic pathways of both entities is of utmost importance and may, in the future, allow development of molecularly targeted therapeutics.
Bilgen Erdoğan; Murat Yılmaz
Burning mouth syndrome is a chronic condition characterized by burning pain without any signs of an oral mucosal pathology, that usually affects postmenopausal women. Burning sensation is often accompanied by dysgeusia and xerostomia. The pathogenesis of the disease is unknown and an effective treatment option for most of the patients has not been defined yet. The aim of this review is to present current pharmacological and physicological treatments of burning mouth syndrome.
Full Text Available Burning mouth syndrome is a chronic condition characterized by burning pain without any signs of an oral mucosal pathology, that usually affects postmenopausal women. Burning sensation is often accompanied by dysgeusia and xerostomia. The pathogenesis of the disease is unknown and an effective treatment option for most of the patients has not been defined yet. The aim of this review is to present current pharmacological and physicological treatments of burning mouth syndrome.
While antibiotics address the root cause of sepsis--that of pathogen infection--they fail to provide an adequate cure for the condition. Currently, 30% to 50% of septic patients die, and this figure is likely to increase in line with the proliferation of multi-drug resistant bacteria. With an increased understanding of the immune response, it has been proposed that modulation of this defence mechanism offers the best hope of cure. Many entry-points in the immune system have been identified and targeted therapies have been developed,but why are these not in routine clinical practice? This review examines the latest evidence for the use of immuno-modulating drugs, obtained from human clinical trials. We discuss cytokine-based therapies, steroids and anti-coagulants. Finally, consideration is given as to why successful therapies in the laboratory, and in vivo models, do not automatically translate into clinical benefit
Lanza, Valeria; Milardi, Danilo; Di Natale, Giuseppe; Pappalardo, Giuseppe
There is mounting urgency to find new drugs for the treatment of neurodegenerative disorders. A large number of reviews have exhaustively described either the molecular or clinical aspects of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD). Conversely, reports outlining how known drugs in use for other diseases can also be effective as therapeutic agents in neurodegenerative diseases are less reported. This review focuses on the current uses of some copper(II) chelating molecules as potential drug candidates in neurodegeneration. Starting from the well-known harmful relationships existing between the dyshomeostasis and mis-management of metals and AD onset, we surveyed the experimental work reported in the literature, which deals with the repositioning of metal-chelating drugs in the field of neurodegenerative diseases. The reviewed papers were retrieved from common literature and their selection was limited to those describing the biomolecular aspects associated with neuroprotection. In particular, we emphasized the copper(II) coordination abilities of the selected drugs. Copper, together with zinc and iron, are known to play a key role in regulating neuronal functions. Changes in copper homeostasis are crucial for several neurodegenerative disorders. The studies included in this review may provide an overview on the current strategies aimed at repurposing copper (II) chelating drugs for the treatment of neurodegenerative disorders. Starting from the exemplary case of clioquinol repurposing, we discuss the challenge and the opportunities that repurposing of other metal-chelating drugs may provide (e.g. PBT-2, metformin and cyclodipeptides) in the treatment of neurodegenerative disease. In order to improve the success rate of drug repositioning, comprehensive studies on the molecular mechanism and therapeutic efficacy are still required. The present review upholds that drug repurposing makes significant advantages over drug discovery since
Ridder, III, William; Karsolia,Apoorva
William H Ridder III, Apoorva Karsolia Southern California College of Optometry, Marshall B Ketchum University, Fullerton, CA, USA Abstract: Dry eye disease (DED) is one of the most commonly encountered conditions for eye care practitioners. The prevalence of DED can be as high as 30% of the population. In the past decade, only one drug has been approved for the treatment of DED by the US Food and Drug Administration (FDA) in the USA (ie, Restasis® by Allergan, Inc.). The total annua...
Oriol, Albert; Motlló, Cristina
Progress in the treatment of multiple myeloma in the last decade has been able to delay, but ultimately not to prevent, the development of resistances and most patients still die of the disease or its related complications. New drugs have been developed including new alkylating agents, proteasome inhibitors and immunomodulators but also monoclonal antibodies and drugs with new mechanisms of action. Hopefully, this new generation of targeted agents will improve the results of the initial therapy, avoid relapses and development of resistances and provide better and less toxic options for the relapsed and refractory patient. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.
Poghosyan, Yuri M; Hakobyan, Koryun A; Poghosyan, Anna Yu; Avetisyan, Eduard K
Retrospective study of jaw osteonecrosis treatment in patients using the "Krokodil" drug from 2009 to 2013. On the territory of the former USSR countries there is widespread use of a self-produced drug called "Krokodil". Codeine containing analgesics ("Sedalgin", "Pentalgin" etc), red phosphorus (from match boxes) and other easily acquired chemical components are used for synthesis of this drug, which used intravenously. Jaw osteonecrosis develops as a complication in patients who use "Krokodil". The main feature of this disease is jawbone exposure in the oral cavity. Surgery is the main method for the treatment of jaw osteonecrosis in patients using "Krokodil". 40 "Krokodil" drug addict patients with jaw osteonecrosis were treated. Involvement of maxilla was found in 11 patients (27.5%), mandible in 21 (52.5%), both jaws in 8 (20%) patients. 35 Lesions were found in 29 mandibles and 21 lesions in 19 maxillas. Main factors of treatment success are: cessation of "Krokodil" use in the pre- (minimum 1 month) and postoperative period and osteonecrosis area resection of a minimum of 0.5 cm beyond the visible borders of osteonecrosis towards the healthy tissues. Surgery was not delayed until sequestrum formation. In the mandible marginal or segmental resection (with or without TMJ exarticulation) was performed. After surgery recurrence of disease was seen in 8 (23%) cases in the mandible, with no cases of recurrence in the maxilla. According to our experience in this case series, surgery is the main method for the treatment of jaw osteonecrosis in patients using "Krokodil". Cessation of drug use and jaw resection minimize the rate of recurrences in such patients. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
Lloyd, Belinda; Zahnow, Renee; Barratt, Monica J; Best, David; Lubman, Dan I; Ferris, Jason
Studies consistently identify substance treatment populations as more likely to die prematurely compared with age-matched general population, with mortality risk higher out-of-treatment than in-treatment. While opioid-using pharmacotherapy cohorts have been studied extensively, less evidence exists regarding effects of other treatment types, and clients in treatment for other drugs. This paper examines mortality during and following treatment across treatment modalities. A retrospective seven-year cohort was utilised to examine mortality during and in the two years following treatment among clients from Victoria, Australia, recorded on the Alcohol and Drug Information Service database by linking with National Death Index. 18,686 clients over a 12-month period were included. Crude (CMRs) and standardised mortality rates (SMRs) were analysed in terms of treatment modality, and time in or out of treatment. Higher risk of premature death was associated with residential withdrawal as the last type of treatment engagement, while mortality following counselling was significantly lower than all other treatment types in the year post-treatment. Both CMRs and SMRs were significantly higher in-treatment than post-treatment. Better understanding of factors contributing to elevated mortality risk for clients engaged in, and following treatment, is needed to ensure that treatment systems provide optimal outcomes during and after treatment. Copyright © 2017 Elsevier Inc. All rights reserved.
Full Text Available Ever since the success of developing inhalable insulin, drug delivery via pulmonary administration has become an attractive route to treat chronic diseases. Pulmonary delivery system for nanotechnology is a relatively new concept especially when applicable to lung cancer therapy. Nano-based systems such as liposome, polymeric nanoparticles or micelles are strategically designed to enhance the therapeutic index of anti-cancer drugs through improvement of their bioavailability, stability and residency at targeted lung regions. Along with these benefits, nano-based systems also provide additional diagnostic advantages during lung cancer treatment, including imaging, screening and drug tracking. Nevertheless, delivery of nano-based drugs via pulmonary administration for lung cancer therapy is still in its infancy and numerous challenges are expected. Pharmacology, immunology, toxicology and large-scale manufacturing (stability and activity of drugs are some aspects in nanotechnology that should be taken into consideration for the development of inhalable nano-based chemotherapeutic drugs. This review will focus on the current inhalable nano-based drugs for lung cancer treatment.
Brunelle, Natacha; Bertrand, Karine; Beaudoin, Isabelle; Ledoux, Cinthia; Gendron, Annie; Arseneault, Catherine
Previous research has documented associations of addiction with delinquency and psychological problems. However, few studies have evaluated their influence on adolescent's drug use trajectories. The current study aims to examine the influence of these factors on the recovery trajectories of 199 youths aged 15.6 years on average admitted to inpatient and outpatient addiction treatment centers, followed up three and six months later. Results indicate that youth who show higher severity of drug abuse exhibit greater improvement than youth with a lower severity of drug abuse at the onset of treatment. Although psychological problems were associated with baseline drug use, they did not influence drug use trajectory over time. Only delinquency influenced the recovery trajectories of these youth. Results suggest that a high level of delinquency can have a significant effect on the drug recovery process of adolescents and that interventions should attempt to reduce both drug use and delinquency. Copyright © 2013 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.
Full Text Available Joseph Jankovic, L Giselle AguilarParkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of MedicineAbstract: Enormous progress has been made in the treatment of Parkinson’s disease (PD. As a result of advances in experimental therapeutics, many promising therapies for PD are emerging. Levodopa remains the most potent drug for controlling PD symptoms, yet is associated with significant complications such as the “wearing off” effect, levodopa-induced dyskinesias and other motor complications. Catechol-o-methyl-transferase inhibitors, dopamine agonists and nondopaminergic therapy are alternative modalities in the management of PD and may be used concomitantly with levodopa or one another. The neurosurgical treatment, focusing on deep brain stimulation, is reviewed briefly. Although this review has attempted to highlight the most recent advances in the treatment of PD, it is important to note that new treatments are not necessarily better than the established conventional therapy and that the treatment options must be individualized and tailored to the needs of each individual patient.Keywords: Parkinson’s disease, levodopa, medical treatment, pallidotomy, deep brain stimulation
The evolution and development of opinions on the diagnosis and treatment of breast cancer since Galen to present time is presented. The concept of breast cancer as a local disease has been replaced by the understanding of its systemic character. On this background described are the methods of surgical treatment beginning from early - supraradical, to present -conservative approaches. The ''milestones'' in diagnosis and treatment of breast cancer of the last 40 years are presented. Current methods of breast cancer management include correct diagnosis (clinical examination, mammography, ultrasound, fine needle aspiration biopsy), TNM staging, adequate loco-regional therapy, systemic therapy, rehabilitation, reconstruction and careful follow-up. (author)
Pasic, Ivan; Lipton, Jeffrey H
Of all the cancers, chronic myeloid leukaemia (CML) has witnessed the most rapid evolution of the therapeutic milieu in recent decades. The introduction of tyrosine kinase inhibitors (TKIs) as a therapeutic option has profoundly changed patient experience and outcome. The availability of multiple new highly effective therapies has increasingly underscored the importance of a good understanding of the underlying pathophysiological basis in CML, as well as patient-specific factors in choosing the right treatment for every individual. The treatment of CML has migrated in many jurisdictions from the office of a highly specialized malignant hematologist to the general hematologist or even a general practitioner. The goal of this review is to offer an overview of the modern approach to the treatment of CML, with an emphasis on chronic phase (CP) CML, including both TKI-based therapies such as imatinib, dasatinib, nilotinib, bosutinib and ponatinib, and non-TKI medications, such as omacetaxine. We discuss evidence behind each drug, most common and material adverse reactions and outline how this information can be used in selecting the right drug for the right patient. We also discuss evidence as it relates to other therapies, including stem cell transplant (SCT), and patients in accelerated (AP) and blastic phase (BP). Copyright © 2017 Elsevier Ltd. All rights reserved.
Andrew S Bell
Full Text Available The evolution of drug resistant Plasmodium parasites is a major challenge to effective malaria control. In theory, competitive interactions between sensitive parasites and resistant parasites within infections are a major determinant of the rate at which parasite evolution undermines drug efficacy. Competitive suppression of resistant parasites in untreated hosts slows the spread of resistance; competitive release following treatment enhances it. Here we report that for the murine model Plasmodium chabaudi, co-infection with drug-sensitive parasites can prevent the transmission of initially rare resistant parasites to mosquitoes. Removal of drug-sensitive parasites following chemotherapy enabled resistant parasites to transmit to mosquitoes as successfully as sensitive parasites in the absence of treatment. We also show that the genetic composition of gametocyte populations in host venous blood accurately reflects the genetic composition of gametocytes taken up by mosquitoes. Our data demonstrate that, at least for this mouse model, aggressive chemotherapy leads to very effective transmission of highly resistant parasites that are present in an infection, the very parasites which undermine the long term efficacy of front-line drugs.
Thevis, Mario; Thomas, Andreas; Schänzer, Wilhelm
With the growing availability of mature systems and strategies in biotechnology and the continuously expanding knowledge of cellular processes and involved biomolecules, human sports drug testing has become a considerably complex field in the arena of analytical chemistry. Proving the exogenous origin of peptidic drugs and respective analogs at lowest concentration levels in biological specimens (commonly blood, serum and urine) of rather limited volume is required to pursue an action against cheating athletes. Therefore, approaches employing chromatographic-mass spectrometric, electrophoretic, immunological and combined test methods have been required and developed. These allow detecting the misuse of peptidic compounds of lower (such as growth hormone-releasing peptides, ARA-290, TB-500, AOD-9604, CJC-1295, desmopressin, luteinizing hormone-releasing hormones, synacthen, etc.), intermediate (e.g., insulins, IGF-1 and analogs, 'full-length' mechano growth factor, growth hormone, chorionic gonadotropin, erythropoietin, etc.) and higher (e.g., stamulumab) molecular mass with desired specificity and sensitivity. A gap between the technically possible detection and the day-to-day analytical practice, however, still needs to be closed.
Full Text Available Aneurysmal bone cysts are benign bone tumors that usually present in childhood and early adulthood. They usually manifest as expansile osteolytic lesions with a varying potential to be locally aggressive. Since their first description in 1942, a variety of treatment methods has been proposed. Traditionally, these tumors were treated with open surgery. Either intralesional surgical procedures or en bloc excisions have been described. Furthermore, a variety of chemical or physical adjuvants has been utilized in order to reduce the risk for local recurrence after excision. Currently, there is a shift to more minimally invasive procedures in order to avoid the complications of open surgical excision. Good results have been reported during percutaneous surgery, or the use of embolization. Recently, sclerotherapy has emerged as a promising treatment, showing effective consolidation of the lesions and functional results that appear to be superior to the ones of open surgery. Lastly, non-invasive treatment, such as pharmaceutical intervention with denosumab or bisphosphonates has been reported to be effective in the management of the disease. Radiotherapy has also been shown to confer good local control, either alone or in conjunction to other treatment modalities, but is associated with serious adverse effects. Here, we review the current literature on the methods of treatment of aneurysmal bone cysts. The indication for each type of treatment along reported outcome of the intervention, as well as potential complications are systematically presented. Our review aims to increase awareness of the different treatment modalities and facilitate decision-making regarding each individual patient.
Gupta, Aditya K; Versteeg, Sarah G; Shear, Neil H
Antifungal agents can be co-administered alongside several other medications for a variety of reasons such as the presence of comorbidities. Pharmacodynamic interactions such as synergistic and antagonistic interactions could be the result of co-administered medications. Pharmacokinetic interactions could also transpire through the inhibition of metabolizing enzymes and drug transport systems, altering the absorption, metabolism and excretion of co-administered medications. Both pharmacodynamic and pharmacokinetic interactions can result in hospitalization due to serious adverse effects associated with antifungal agents, lower therapeutic doses required to achieve desired antifungal activity, and prevent antifungal resistance. Areas covered: The objective of this review is to summarize pharmacodynamic and pharmacokinetic interactions associated with common antifungal agents used to treat superficial fungal infections. Pharmacodynamic and pharmacokinetic interactions that impact the therapeutic effects of antifungal agents and drugs that are influenced by the presence of antifungal agents was the context to which these antifungal agents were addressed. Expert opinion: The potential for drug-drug interactions is minimal for topical antifungals as opposed to oral antifungals as they have minimal exposure to other co-administered medications. Developing non-lipophilic antifungals that have unique metabolizing pathways and are topical applied are suggested properties that could help limit drug-drug interactions associated with future treatments.
Park, John W
Drug delivery systems can in principle provide enhanced efficacy and/or reduced toxicity for anticancer agents. Long circulating macromolecular carriers such as liposomes can exploit the 'enhanced permeability and retention' effect for preferential extravasation from tumor vessels. Liposomal anthracyclines have achieved highly efficient drug encapsulation, resulting in significant anticancer activity with reduced cardiotoxicity, and include versions with greatly prolonged circulation such as liposomal daunorubicin and pegylated liposomal doxorubicin. Pegylated liposomal doxorubucin has shown substantial efficacy in breast cancer treatment both as monotherapy and in combination with other chemotherapeutics. Additional liposome constructs are being developed for the delivery of other drugs. The next generation of delivery systems will include true molecular targeting; immunoliposomes and other ligand-directed constructs represent an integration of biological components capable of tumor recognition with delivery technologies
... poisoning and unapproved injectable drug products containing sodium thiosulfate labeled for the treatment of... for the treatment of cyanide poisoning are new drugs that require approved new drug applications (NDAs... Injection and Sodium Thiosulfate Injection drug product, labeled for treatment of acute cyanide poisoning...
This is a brief review of the current status of radiation treatment of surface water, groundwater, wastewaters, and sewage sludges. Sources of ionizing radiation, and combination radiation methods for purification are described in some detail. Special attention is paid to pilot and industrial facilities. (author)
Full Text Available Auditory hallucinations (AH are a symptom of several psychiatric disorders, such as schizophrenia. In a significant minority of patients, AH are resistant to antipsychotic medication. Alternative treatment options for this medication-resistant group are scarce and most of them focus on coping with the hallucinations. Finding an alternative treatment that can diminish AH is of great importance.Transcranial direct current stimulation (tDCS is a safe and non-invasive technique that is able to directly influence cortical excitability through the application of very low electric currents. A 1-2 mA direct current is applied between two surface electrodes, one serving as the anode and the other as the cathode. Cortical excitability is increased in the vicinity of the anode and reduced near the cathode. The technique, which has only a few transient side effects and is cheap and portable, is increasingly explored as a treatment for neurological and psychiatric symptoms. It has shown efficacy on symptoms of depression, bipolar disorder, schizophrenia, Alzheimer’s disease, Parkinson’s disease, epilepsy and stroke. However, the application of tDCS as a treatment for AH is relatively new. This article provides an overview of the current knowledge in this field and provides guidelines for future research.
Yang, Caijun; Wu, Lina; Cai, Wenfang; Zhu, Wenwen; Shen, Qian; Li, Zongjie; Fang, Yu
Drug shortages were a complex global problem. The aim of this study was to analyze, characterize, and assess the drug shortages, and identify possible solutions in Shaanxi Province, western China. A qualitative methodological approach was conducted during May-June 2015 and December 2015-January 2016. Semi-structured interviews were performed to gather information from representatives of hospital pharmacists, wholesalers, pharmaceutical producers, and local health authorities. Thirty participants took part in the study. Eight traditional Chinese medicines and 87 types of biologicals and chemicals were reported to be in short supply. Most were essential medicines. Five main determinants of drug shortages were detected: too low prices, too low market demands, Good Manufacturing Practice (GMP) issues, materials issues, and approval issues for imported drugs. Five different solutions were proposed by the participants: 1) let the market decide the drug price; 2) establish an information platform; 3) establish a reserve system; 4) enhance the communication among the three parties in the supply chain; and 5) improve hospital inventory management. Western China was currently experiencing a serious drug shortage. Numerous reasons for the shortage were identified. Most drug shortages in China were currently because of "too low prices." To solve this problem, all of the stakeholders, especially the government, needed to participate in managing the drug shortages.
Guzman-Aranguez, Ana; Fonseca, Begoña; Carracedo, Gonzalo; Martin-Gil, Alba; Martinez-Aguila, Alejandro; Pintor, Jesús
Dry eye disease affects a substantial segment of the word population with increasing frequency. It is a multifactorial disease of the ocular surface and tear film, which causes ocular discomfort, visual disturbances, and tear instability with potential damage to the cornea and conjunctiva. Because of its multifactorial etiology, the use of different pharmacological treatment for dry eye treatment has been proposed, which include anti-inflammatory molecules, lubricants or comfort agents, and secretagogues. However, in some cases these pharmacological approaches only relieve symptoms temporarily, and consequently, eye care professionals continue to have difficulties managing dry eye. To improve pharmacological therapy that allows a more efficient and long-term action, effective ocular drug delivery of the currently available drugs for dry eye treatment is required. Contact lenses are emerging as alternative ophthalmic drugs delivery systems that provide an increased residence time of the drug at the eye, thus leading to enhanced bioavailability and more convenient and efficacious therapy. In this article, we reviewed the different techniques used to prepare contact lens-based drug delivery systems and focused on articles that describe the delivery of compounds for dry eye treatment through contact lenses.
Schiffer, Wynne K. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)], E-mail: firstname.lastname@example.org; Liebling, Courtney N.B.; Patel, Vinal; Dewey, Stephen L. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)
Although imaging studies in and of themselves have significant contributions to the study of human behavior, imaging in drug abuse has a much broader agenda. Drugs of abuse bind to molecules in specific parts of the brain in order to produce their effects. Positron emission tomography (PET) provides a unique opportunity to track this process, capturing the kinetics with which an abused compound is transported to its site of action. The specific examples discussed here were chosen to illustrate how PET can be used to map the regional distribution and kinetics of compounds that may or may not have abuse liability. We also discussed some morphological and functional changes associated with drug abuse and different stages of recovery following abstinence. PET measurements of functional changes in the brain have also led to the development of several treatment strategies, one of which is discussed in detail here. Information such as this becomes more than a matter of academic interest. Such knowledge can provide the bases for anticipating which compounds may be abused and which may not. It can also be used to identify biological markers or changes in brain function that are associated with progression from drug use to drug abuse and also to stage the recovery process. This new knowledge can guide legislative initiatives on the optimal duration of mandatory treatment stays, promoting long-lasting abstinence and greatly reducing the societal burden of drug abuse. Imaging can also give some insights into potential pharmacotherapeutic targets to manage the reinforcing effects of addictive compounds, as well as into protective strategies to minimize their toxic consequences.
Schiffer, Wynne K.; Liebling, Courtney N.B.; Patel, Vinal; Dewey, Stephen L.
Although imaging studies in and of themselves have significant contributions to the study of human behavior, imaging in drug abuse has a much broader agenda. Drugs of abuse bind to molecules in specific parts of the brain in order to produce their effects. Positron emission tomography (PET) provides a unique opportunity to track this process, capturing the kinetics with which an abused compound is transported to its site of action. The specific examples discussed here were chosen to illustrate how PET can be used to map the regional distribution and kinetics of compounds that may or may not have abuse liability. We also discussed some morphological and functional changes associated with drug abuse and different stages of recovery following abstinence. PET measurements of functional changes in the brain have also led to the development of several treatment strategies, one of which is discussed in detail here. Information such as this becomes more than a matter of academic interest. Such knowledge can provide the bases for anticipating which compounds may be abused and which may not. It can also be used to identify biological markers or changes in brain function that are associated with progression from drug use to drug abuse and also to stage the recovery process. This new knowledge can guide legislative initiatives on the optimal duration of mandatory treatment stays, promoting long-lasting abstinence and greatly reducing the societal burden of drug abuse. Imaging can also give some insights into potential pharmacotherapeutic targets to manage the reinforcing effects of addictive compounds, as well as into protective strategies to minimize their toxic consequences
Maze, M J; Paynter, J; Chiu, W; Hu, R; Nisbet, M; Lewis, C
There is uncertainty as to the optimal therapeutic concentrations of anti-tuberculosis drugs to achieve cure. To characterise the use of therapeutic drug monitoring (TDM), and identify risk factors and outcomes for those with concentrations below the drug interval. Patients treated for tuberculosis (TB) who had rifampicin (RMP) or isoniazid (INH) concentrations measured between 1 January 2005 and 31 December 2012 were studied retrospectively. Matched concentrations and drug dosing time were assessed according to contemporary regional drug intervals (RMP > 6 μmol/l, INH > 7.5 μmol/l) and current international recommendations (RMP > 10 μmol/l, INH > 22 μmol/l). Outcomes were assessed using World Health Organization criteria. Of 865 patients, 121 had concentrations of either or both medications. RMP concentrations were within the regional drug intervals in 106/114 (93%) and INH in 91/100 (91%). Concentrations were within international drug intervals for RMP in 76/114 (67%) and INH in 53/100 (53%). Low weight-based dose was the only statistically significant risk factor for concentrations below the drug interval. Of the 35 patients with low concentrations, 21 were cured, 9 completed treatment and 5 transferred out. There were no relapses during follow-up (mean 66.5 months). There were no clinically useful characteristics to guide use of TDM. Many patients had concentrations below international therapeutic intervals, but were successfully treated.
Spagnolo, Primavera A; Colloca, Luana; Heilig, Markus
Throughout history, patient-physician relationships have been acknowledged as an important component of the therapeutic effects of any pharmacological treatment. Here, we discuss the role of physicians' expectations in influencing the therapeutic outcomes of alcohol and drug addiction pharmacological treatments. As largely demonstrated, such expectations and attitudes may contribute to produce placebo and nocebo effects that in turn affect the course of the disease and the response to the therapy. This article is aimed at discussing the current insights into expectations, placebo and nocebo mechanisms and their impact on the therapeutic outcomes of alcohol and drug addiction treatments; with the goal of informing physicians and other health care providers about the potentially widespread implications for clinical practice and for a successful treatment regimen. Published by Oxford University Press on behalf of Medical Council on Alcohol 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Filges, Trine; Knudsen, Anne-Sofie Due; Svendsen, Majken
), Multidimensional Family Therapy (MDFT), and Psychoeducational Therapy (PET)). RESULTS Our main objective was to evaluate the current evidence on the effect of CBT on abstinence and drug use reduction for young people in outpatient treatment for non-opioid drug use. Seven randomised trials, involving 953......, and PET ) with respect to reduction in young people’s drug use. The evidence drawn from this systematic review is based on seven included studies analysed in two separate analyses, depending on whether the intervention was CBT with an add-on component such as motivational interviewing (four studies......) or CBT without an add-on component (three studies). The seven studies are very different in terms of their findings regarding the effects of CBT interventions compared to other interventions (ACRA, CBOP (+ACC), DHPE, FFT, IT, MDFT, and PET ) on young people’s drug use. Therefore, the overall conclusion...
Muddineti, Omkara Swami; Ghosh, Balaram; Biswas, Swati
Owing to the complexity of cancer pathogenesis, conventional chemotherapy can be an inadequate method of killing cancer cells effectively. Nanoparticle-based drug delivery systems have been widely exploited pre-clinically in recent years. Areas covered: Incorporation of vitamin-E in nanocarriers have the advantage of (1) improving the hydrophobicity of the drug delivery system, thereby improving the solubility of the loaded poorly soluble anticancer drugs, (2) enhancing the biocompatibility of the polymeric drug carriers, and (3) improving the anticancer potential of the chemotherapeutic agents by reversing the cellular drug resistance via simultaneous administration. In addition to being a powerful antioxidant, vitamin E demonstrated its anticancer potential by inducing apoptosis in various cancer cell lines. Various vitamin E analogs have proven their ability to cause marked inhibition of drug efflux transporters. Expert opinion: The review discusses the potential of incorporating vitamin E in the polymeric micelles which are designed to carry poorly water-soluble anticancer drugs. Current applications of various vitamin E-based polymeric micelles with emphasis on the use of α-tocopherol, D-α-tocopheryl succinate (α-TOS) and its conjugates such as D-α-tocopheryl polyethylene glycol-succinate (TPGS) in micellar system is delineated. Advantages of utilizing polymeric micelles for drug delivery and the challenges to treat cancer, including multiple drug resistance have been discussed.
Full Text Available Background: Drug craving is considered as one of the main cores of drug dependency and addiction. Multidimensionality of drug craving, its cultural-bounded features and its intra individual rapidly changing nature makes it difficult to be measured. Nowadays, regarding different psychometric approaches, there are various instruments available for measurement of different aspects of drug craving but mainly for Latin-based languages in North America and European countries. High prevalence and special conditions, and unique subcultures in substance abuse and addiction in many countries, like Iran, make the design of culturally validated instruments for drug craving assessment priority. Materials and Methods: Comprehensive review on drug craving measurement instruments for Persian speaking subjects have been performed by searching in databases (ELSEVIER, Science Direct and Scientific Information Database (SID and investigating of related documents on regional experiences. Results: In this article seven main categories of drug craving instruments have been reviewed focusing on validated versions in Persian language including: self-reports, reinforcement “proxies”, drug self administration, psycho physiological responding, neurobiological responding, cognitive processing and expressive methods. Conclusion: Reviewing on weak and strength points of each instrument group and national and regional experiences shows that designing and validating a new series of ecologically-validated instruments for multidimensional measurement of drug craving in different addiction subcultures should be prioritized to cover current methodological gaps in substance abuse studies in Iran.
The Food and Drug Administration (FDA) is amending the current good manufacturing practice (CGMP) regulations for human drugs, including biological products, to exempt most phase 1 investigational drugs from complying with the regulatory CGMP requirements. FDA will continue to exercise oversight of the manufacture of these drugs under FDA's general statutory CGMP authority and through review of the investigational new drug applications (IND). In addition, elsewhere in this issue of the Federal Register, FDA is announcing the availability of a guidance document entitled "Guidance for Industry: CGMP for Phase 1 Investigational Drugs" dated November 2007 (the companion guidance). This guidance document sets forth recommendations on approaches to compliance with statutory CGMP for the exempted phase 1 investigational drugs. FDA is taking this action to focus a manufacturer's effort on applying CGMP that is appropriate and meaningful for the manufacture of the earliest stage investigational drug products intended for use in phase 1 clinical trials while ensuring safety and quality. This action will also streamline and promote the drug development process.
Modric, T; Momcilovic, D; Gwin, W E; Peter, A T
Hormonal and antimicrobial therapies are essential to regulate and maintain healthy reproduction in domestic animals. The appropriate and legal use of these compounds is ultimately the responsibility of the veterinarian and other users, with a primary mission to directly protect and promote the health of animals, and indirectly the health of people. The appropriate use of these products is defined by the Federal Food, Drug, and Cosmetic Act, 21 United States of America § 301 et seq and implementing regulations in the Code of Federal Regulations. In the past, use of a drug in an animal for an unapproved use violated this Act. However, passage of the Animal Medicinal Drug Use Clarification Act 1994 legalized the extra-label use of certain animal and human drugs in veterinary practice for treating diseases. This manuscript reviews currently approved hormonal and antimicrobial drugs for use in theriogenology. Considering the ever increasing knowledge in the area of veterinary reproduction, particularly in the treatment and control of reproduction using antimicrobials and hormones, it would be beneficial to widen the therapeutic options in these categories. The potential for widening the therapeutic options is also discussed in this review, by providing a non-exhaustive but essential list of potential new drugs for use in clinical animal reproduction (theriogenology). Copyright © 2011 Elsevier Inc. All rights reserved.
Irrational drug use in neuropathic pain treatment: a twoyear data analysis. E Tan, A Akıncı, G Ayvaz, T Erbaş, M Ertaş, O Güç, S Hepgüler, S Kiraz, SZ Oşar, S Öztürk, NS Özyalçın, S Palaoğlu, M Uyar, S Ünal, S Yalçın ...
Full Text Available Background. The standard treatment of a new case of multidrug-resistant tuberculosis (MDR-TB according to WHO recommendations in the Republic of Moldova is performed since 2005 showing a low treatment succes. Actually the treatment success rate increased due to excluding of MDR-TB patients from the general cohort. The major rate of patients with low outcome is represented by the failed and lost to follow-up cases. The purpose of the study was to assess the impact of multidrug-resiatnce and MDR-TB on the tuberculosis treatment outcome. Materials and methods. A retrospective selective, descriptive study targeting social, demographic, economic and epidemiological peculiarities, case-management, diagnostic radiological aspects and microbiological characteristics of 187 patients with pulmonary tuberculosis registered during 2013–2015 distributed in two groups: 1st group (61 patients with established multidrug-resistant strains using conventional cultural methods and the 2nd group (126 patients with MDR-TB. Results. Multidrug-resistance was established more frequently in new cases and MDR-TB in two thirds of retreated patients. No difference was identified in gender and age distribution, social, economical, educational characteristics; case-management assessment identified a similar proportion of patients revealed by general practitioners and specialists, with low rate of screened high risk groups. All patients from the multidrug-resistant group began the standard treatment for drug-responsiveness tuberculosis before drug susceptibility testing and one third of MDR-TB group was treated from the onset with the DOTS-Plus regimen. Highest success rate was identified in the new-case subgroups of both groups and higher rate of died patients was determined in the retreated subgroups. Such a low rate of patients aggrevates the resistance. Conclusions. Early diagnosis, drug responsiveness testing and raising awareness among about treatment compliance will
Baumbach, S F; Michel, M; Wyen, H; Buschmann, C T; Kdolsky, R; Kanz, K-G
The limited evidence available on the diagnosis and treatment of olecranon and prepatellar bursitis indicates nationally varying treatment approaches. Therefore the aim of this study was to survey the current treatment concepts of olecranon and prepatellar bursitis in Austria. An online questionnaire comprising of demographic data, questions regarding diagnostics and differentiation between septic bursitis (SB) and non-septic bursitis (NSB) as well as two case reports for therapy appraisal were sent to members of the Austrian Society of Orthopaedics and Orthopaedic Surgery (ÖGO) and the Austrian Society of Traumatology (ÖGU). The overall response rates were 46 % (ÖGU)/12 % (ÖGO). Differentiation between SB and NSB was predominantly based on medical history/clinical presentation (ÖGU: 100 %/ÖGO: 84 %) and blood sampling (ÖGU: 82 %/ÖGO: 77 %). 64/36 % of surveyed members of ÖGO/OGU performed a bursal aspiration. 95/55 % of Austrian ÖGU opinion leaders favoured a surgical treatment approach in cases of SB/NSB. Conversely, ÖGO members rather favoured a conservative treatment approach (28/27 %). Significant differences were found between ÖGO and ÖGU, with the latter favouring a surgical treatment approach in cases of SB and NSB. However, the international literature argues for a conservative treatment approach. Further high quality research is needed to establish an evidence-based treatment approach. Georg Thieme Verlag KG Stuttgart · New York.
Vyas, Amber; Kumar Sonker, Avinesh
Approximately 95% of the population suffers at some point in their lifetime from acne vulgaris. Acne is a multifactorial disease of the pilosebaceous unit. This inflammatory skin disorder is most common in adolescents but also affects neonates, prepubescent children, and adults. Topical conventional systems are associated with various side effects. Novel drug delivery systems have been used to reduce the side effect of drugs commonly used in the topical treatment of acne. Topical treatment of acne with active pharmaceutical ingredients (API) makes direct contact with the target site before entering the systemic circulation which reduces the systemic side effect of the parenteral or oral administration of drug. The objective of the present review is to discuss the conventional delivery systems available for acne, their drawbacks, and limitations. The advantages, disadvantages, and outcome of using various carrier-based delivery systems like liposomes, niosomes, solid lipid nanoparticles, and so forth, are explained. This paper emphasizes approaches to overcome the drawbacks and limitations associated with the conventional system and the advances and application that are poised to further enhance the efficacy of topical acne formulations, offering the possibility of simplified dosing regimen that may improve treatment outcomes using novel delivery system. PMID:24688376
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.
Rogoff, Edward G; Guirguis, Hany S; Lipton, Richard A; Seremetis, Stephanie V; DiMichele, Donna M; Agnew, George M; Karpatkin, Margaret; Barish, Robert J; Jones, Robert L; Bianco, Celso; Knothe, Barbara D; Lee, Myung-Soo
Hemophilia is an expensive disease because its treatment is heavily dependent on costly clotting factor drugs. Over the last nine years,a consortium of three Comprehensive Hemophilia Treatment Centers and other hospitals, which purchased clotting factors for their patients, has seen treatment costs escalate on average 17% annually. Currently, new, even more expensive drugs are entering the market. This study analyzes 3,244 purchases that were made over a nine-year period totaling nearly 500 million units of clotting factor, representing every product on the market. Purchases were made both apart from and under the Federal Public Health Service (PHS)discount pricing rules. The main cause of the increases was the move to newer, more expensive products. The average price of existing products increased less than 2%per year, but new products were priced, on average, 47% higher than existing products. Overall consumption increased by an average of 5% per year, likely reflecting prophylactic treatment modalities that require greater amounts of clotting factor. Government pricing programs, such as the PHS program, were ineffective or counterproductive at reducing costs. There is a notable absence of competition in this market, with a few dominant companies having a functional monopoly in the largest segments of the market. Prices of older products are not lowered, even when new products are brought to market. A few products that serve small patient groups have had their prices increased substantially. This escalation is likely to continue as new, more expensive clotting factor drugs are developed. Since these new products are not proven to be any safer or more effective than the current products, this situation creates a risk of intervention by government and insurers to address both treatment costs and exhaustion of patients' insurance caps. Drug companies are not serving the patients by pricing new, but often very similar, products so aggressively. The trends seen in
Neralla, Sridhar; Meyer, Keith C
risk factors for DRSP. A chest x-ray is recommended for all patients, but other testing such as obtaining a sputum Gram's smear is not necessary and should not prolong the time gap between clinical suspicion of pneumonia and antibacterial administration. The selection of antibacterials should be based upon local resistance patterns of suspected organisms and the bactericidal efficacy of the chosen drugs. If time-dependent agents are chosen and DRSP are possible pathogens, dosing should keep drug concentrations above the minimal inhibitory concentration that is effective for DRSP. Treatment guidelines and recent studies suggest that combination therapy with a beta-lactam and macrolide may be associated with a better outcome in hospitalised patients, and overuse of fluoroquinolones as a single agent may promote quinolone resistance. The ketolides represent a new class of macrolide-like antibacterials that are highly effective in vitro against macrolide- and azalide-resistant pneumococci. Pneumococcal vaccination with the currently available polysaccharide vaccine is thought to confer some preventive benefit (preventing invasive pneumococcal disease), but more effective vaccines, such as nonconjugate protein vaccines, need to be developed that provide broad protection against pneumococcal infection.
Tiffany A. Brown
Full Text Available Eating disorders are a significant source of psychiatric morbidity in young women and demonstrate high comorbidity with mood, anxiety, and substance use disorders. Thus, clinicians may encounter eating disorders in the context of treating other conditions. This review summarizes the efficacy of current and emerging treatments for anorexia nervosa (AN, bulimia nervosa (BN, and binge eating disorder (BED. Treatment trials were identified using electronic and manual searches and by reviewing abstracts from conference proceedings. Family based therapy has demonstrated superiority for adolescents with AN but no treatment has established superiority for adults. For BN, both 60 mg fluoxetine and cognitive behavioral therapy (CBT have well-established efficacy. For BED, selective serotonin reuptake inhibitors, CBT, and interpersonal psychotherapy have demonstrated efficacy. Emerging directions for AN include investigation of the antipsychotic olanzapine and several novel psychosocial treatments. Future directions for BN and BED include increasing CBT disseminability, targeting affect regulation, and individualized stepped-care approaches.
van Wormer, Katherine; Persson, Lance Edwards
A large percentage of inmates in the U.S. federal prison system have serious drug problems and are in need of treatment before they return to society. Accordingly, the Federal Bureau of Prisons has revamped substance abuse programming consistent with the latest research and expanded treatment services throughout its institutions. This article…
Lee, Michelle; Winkler, Johnathon; Hartwell, Gary; Stewart, Jeffrey; Caine, Rufus
The current clinical practice of endodontics includes the utilization of a variety of new technological advances and materials. The last comprehensive survey that compared treatment modalities used in endodontic practices was conducted in 1990. The purpose of the current survey was to determine the frequency with which these new endodontic technologies and materials are being used in endodontic practices today. An e-mail questionnaire was sent to the 636 active diplomates of the American Board of Endodontics with current e-mail addresses. Two hundred thirty-two diplomates responded for a response rate of 35%. Calcium hydroxide was found to be the most frequently used intracanal medicament for all cases diagnosed with necrotic pulps. Ibuprofen was the most frequently prescribed medication for pain, and penicillin was the most frequently prescribed antibiotic when an active infection was present. Eighty-two percent of the respondents are still incorporating hand files in some fashion during the cleansing and shaping phase of treatment. Lateral condensation and continuous wave were the most common methods used for obturation. Digital radiography was reported as being used by 72.5% of the respondents, whereas 45.3% reported using the microscope greater than 75% of the patient treatment. Ultrasonics was used by 97.8% of the respondents. It appears from the results that new endodontic technology is currently being used in the endodontic offices of those who responded to the survey.
Vallecillo, Gabriel; Mojal, Sergio; Roquer, Albert; Samos, Pilar; Luque, Sonia; Martinez, Diana; Martires, Paula Karen; Torrens, Marta
Continuous HIV treatment is necessary to ensure successful combined antiretroviral therapy (cART). The aim of this study was to evaluate the incidence of patient-initiated non-structured treatment interruptions in HIV-infected persons who inject drugs and who received a multidisciplinary comprehensive program, including medical HIV care, drug-dependence treatment and psychosocial support, at a drug outpatient addiction center. Non-structured treatment interruptions were defined as ≥30 consecutive days off cART without medical indication. During a median follow-up of 53.8 months, 37/132 (28 %) patients experienced the first non-structured treatment interruptions. The cumulative probability of cART interruption at 5 years was 31.2 % (95 % CI 22.4-40.0). Current drug use injection ≥1/day (HR 14.77; 95 % CI 5.90-36.96) and cART naive patients (HR 0.35, 95 % CI 0.14-0.93) were predictive factors for non-structured treatment interruptions. HIV care provided at a drug addiction center is a useful strategy to sustain continuous cART, however, drug abstinence is essential for the long-term maintenance of cART.
Mohamad Rasm Al Sibae
Full Text Available Mohamad Rasm Al Sibae, Brendan M McGuireDepartment of Medicine, Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, USAAbstract: Hepatic encephalopathy (HE is a common reversible neuropsychiatric syndrome associated with chronic and acute liver dysfunction and significant morbidity and mortality. Although a clear pathogenesis is yet to be determined, elevated ammonia in the serum and central nervous system are the mainstay for pathogenesis and treatment. Management includes early diagnosis and prompt treatment of precipitating factors (infection, gastrointestinal bleeding, electrolyte disturbances, hepatocellular carcinoma, dehydration, hypotension, and use of benzodiazepines, psychoactive drugs, and/or alcohol. Clinical trials have established the efficacy of lactulose and lactitol enemas in the treatment of acute hepatic encephalopathy. Extensive clinical experience has demonstrated the efficacy of oral lactulose and lactitol with the goal of two to three soft bowel movements a day for the treatment of chronic HE. However, lactulose and lactitol have significant gastrointestinal side effects. For patients unable to tolerate lactulose or lactitol or who still have persistent chronic HE with lactulose or lactitol, neomycin, metronidazole and rifaximin are second-line agents. More recent data supports the benefits of rifaximin used solely and as an additional agent with fewer side effects than neomycin or metronidazole. Newer therapies being investigated in humans with clinical promise include nitazoxanide, the molecular adsorbent recirculating system (MARS, L-ornithine phenylacetate, sodium benzoate, and/or sodium phenylacetate and Kremezin® (AST-120.Keywords: hepatic encephalopathy, liver dysfunction, lactulose, lactitol
Dinh, A; Bouchand, F; Le Monnier, A
During the past 10years, Clostridium difficile infections (CDI) have become a major public health challenge. Their epidemiology has changed with a rise in the number of cases and an increase in severe episodes. Recurrence and failure of conventional treatments have become more common. Furthermore, a spread of CDI has been observed in the general population-involving subjects without the usual risk factors (unexposed to antibiotic treatment, young people, pregnant women, etc.). All these change are partially due to the emergence of the hypervirulent and hyperepidemic clone NAP1/B1/027. New therapeutic strategies (antimicrobial treatment, immunoglobulins, toxin chelation, fecal microbiota transplantation) are now available and conventional treatments (metronidazole and vancomycin) have been reevaluated with new recommendations. Recent studies show a better efficacy of vancomycin compared to metronidazole for severe episodes. Fidaxomicin is a novel antibiotic drug with interesting features, including an efficacy not inferior to vancomycin and a lower risk of recurrence. Finally, for multi-recurrent forms, fecal microbiota transplantation seems to be the best option. We present the available data in this review. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.
Psoriasis is a chronic and complex autoimmune inflammatory skin disease that affects over 125 million people worldwide. It can exhibit at any age, in spite of the fact that children are less normally influenced than adults. It is characterized by distinct erythematous plaques shielded with conspicuous silvery scales that shows up in different areas of the skin. Knowledge of pathophysiology, especially the pathogenesis of psoriasis, has significantly progressed in the recent decade. Advancement in molecular knowledge leads to better understanding of the disease, thus influencing the development of efficient treatment modalities. However, even with the availability of various options of treatment most of the efficient treatment modalities are costly. Expenses of health care bring about major financial weight to the patients as well as to health care systems. Thus, it was important to review the available current treatment options and those which are under development, in terms of efficacy, safety and cost to assist in selecting the most appropriate treatment for psoriasis patients. Literatures were searched by using key words psoriasis, topical treatment, systemic treatment, biologics and phototherapies, on Embase, Medline, Jstor, Cochrane and Merck Index databases. Life-style choices such as smoking, alcohol consumption, obesity and stress are recognised as risk factors and triggers associated with psoriasis. Psoriasis poses psycho-social and economic burden on affected patients that sometimes leads to depression, reduced social interaction and suicidal tendencies in patients. Depending on the type, severity and extent of the disease, comorbidities, patient preference, efficacy and safety profile, numerous treatment modalities and therapeutic agents are available such as topical, systemic, biologic and phototherapeutic treatments. However, it was found that among all the current available treatments for psoriasis, biologic agents and phototherapeutic modalities are
Full Text Available Patrick J Richard, Ramesh Rengan Department of Radiation Oncology, University of Washington, Seattle, WA, USA Abstract: The oligometastatic disease theory was initially described in 1995 by Hellman and Weichselbaum. Since then, much work has been performed to investigate its existence in many solid tumors. This has led to subclassifications of stage IV cancer, which could redefine our treatment approaches and the therapeutic outcomes for this historically “incurable” entity. With a high incidence of stage IV disease, non-small-cell lung cancer (NSCLC remains a difficult cancer to treat and cure. Recent work has proven the existence of an oligometastatic state in NSCLC in terms of properly selecting patients who may benefit from aggressive therapy and experience long-term overall survival. This review discusses the current treatment approaches used in oligometastatic NSCLC and provides the evidence and rationale for each approach. The prognostic factors of many trials are discussed, which can be used to properly select patients for aggressive treatment regimens. Future advances in both molecular profiling of NSCLC to find targetable mutations and investigating patient selection may increase the number of patients diagnosed with oligometastatic NSCLC. As this disease entity increases, it is of utmost importance for oncologists treating NSCLC to be aware of the current treatment strategies that exist and the potential advantages/disadvantages of each. Keywords: oligometastatic, non-small-cell lung cancer, oligoprogressive, treatment
Barry, Colleen L; McGinty, Emma Elizabeth; Pescosolido, Bernice; Goldman, Howard H.
Objective This study compares current public attitudes about drug addiction with attitudes about mental illness. Methods A web-based national public opinion survey (N=709) was conducted to compare attitudes about stigma, discrimination, treatment effectiveness, and policy support. Results Respondents hold significantly more negative views toward persons with drug addiction compared to those with mental illness. More respondents were unwilling to have a person with drug addiction marry into their family or work closely with them on a job. Respondents were more willing to accept discriminatory practices, more skeptical about the effectiveness of available treatments, and more likely to oppose public policies aimed at helping persons with drug addiction. Conclusions Drug addiction is often treated as a sub-category of mental illness, and health insurance benefits group these conditions together under the rubric of behavioral health. Given starkly different public views about drug addiction and mental illness, advocates may need to adopt differing approaches for advancing stigma reduction and public policy. PMID:25270497
Lindsay P Bodell
Full Text Available Lindsay P Bodell, Pamela K KeelDepartment of Psychology, Florida State University, Tallahassee, FL, USAAbstract: Anorexia nervosa (AN is a serious psychiatric illness associated with significant medical and psychiatric morbidity, psychosocial impairment, increased risk of death, and chronicity. Given the severity of the disorder, the establishment of safe and effective treatments is necessary. Several treatments have been tried in AN, but few favorable results have emerged. This paper reviews randomized controlled trials in AN, and provides a synthesis of existing data regarding the efficacy, safety, and adherence associated with pharmacologic and psychological interventions. Randomized controlled trials for the treatment of AN published in peer-reviewed journals were identified by electronic and manual searches. Overall, pharmacotherapy has limited benefits in the treatment of AN, with some promising preliminary findings associated with olanzapine, an antipsychotic agent. No single psychological intervention has demonstrated clear superiority in treating adults with AN. In adolescents with AN, the evidence base is strongest for the use of family therapy over alternative individual psychotherapies. Results highlight challenges in both treating individuals with AN and in studying the effects of those treatments, and further emphasize the importance of continued efforts to develop novel interventions. Treatment trials currently underway and areas for future research are discussed.Keywords: anorexia nervosa, treatment, pharmacotherapy, psychotherapy, randomized controlled trials
Wu, Di; Si, Mengjie; Xue, Hui-Yi; Wong, Ho-Lun
Breast cancer is the most common malignant disease in women worldwide, but the current drug therapy is far from optimal as indicated by the high death rate of breast cancer patients. Nanomedicine is a promising alternative for breast cancer treatment. Nanomedicine products such as Doxil ® and Abraxane ® have already been extensively used for breast cancer adjuvant therapy with favorable clinical outcomes. However, these products were originally designed for generic anticancer purpose and not specifically for breast cancer treatment. With better understanding of the molecular biology of breast cancer, a number of novel promising nanotherapeutic strategies and devices have been developed in recent years. In this review, we will first give an overview of the current breast cancer treatment and the updated status of nanomedicine use in clinical setting, then discuss the latest important trends in designing breast cancer nanomedicine, including passive and active cancer cell targeting, breast cancer stem cell targeting, tumor microenvironment-based nanotherapy and combination nanotherapy of drug-resistant breast cancer. Researchers may get insight from these strategies to design and develop nanomedicine that is more tailored for breast cancer to achieve further improvements in cancer specificity, antitumorigenic effect, antimetastasis effect and drug resistance reversal effect.
Elisaldo A. Carlini
Full Text Available The topic "Herbal Medicines in the Treatment of Addictions" in a country must be preceded by answers to four questions: 1. Does the country in question possess a biodiversity rich enough to allow the discovery of useful medicines? 2. Do local people have tradition and culture to look for and use resources from Nature to alleviate and cure diseases, including drug dependence? 3. Is drug dependence (or addiction present in the country in question? 4. Do people of that country recognize and diagnose such problem as a serious one? Alcohol is, by far, the most serious health problem when drug abuse is considered, reaching all of Brazilian society, including the Indians. On the contrary, other drugs may be considered as minor problems and they are not the main focus of this manuscript. The people living in Brazilian hinterland don’t have access to public health systems. Consequently, these people seek assistance from "curandeiros" and "raizeiros"; the Indians are assisted by the shaman. These "folk doctors" do not know the academic medicine and therapeutics, and resort to the local plants to treat different ailments of their patients. Furthermore, alcohol abuse and dependence are not recognized by them, according to the rules and criteria of academic medicine. We have conducted a survey in many Brazilian books, Thesis concerning phytotherapy, and several databank. The results of such searches were very disappointing. No published papers from Brazilian authors concerning the use of plants for the treatment of addictions were found in the databases and there were only three very short notes in the masterly book written by Shultes and Raffauf (1990. From the Brazilian books on folk medicine employing medicinal plants, ten mentions were disclosed: most of them dealing with treatment of alcohol problems and two to counteract "Ayahuasca" dependence.
Mapara, Sanyat S; Patravale, Vandana B
The advancements in electronics and the progress in nanotechnology have resulted in path breaking development that will transform the way diagnosis and treatment are carried out currently. This development is Medical Capsule Robots, which has emerged from the science fiction idea of robots travelling inside the body to diagnose and cure disorders. The first marketed capsule robot was a capsule endoscope developed to capture images of the gastrointestinal tract. Today, varieties of capsule endoscopes are available in the market. They are slightly larger than regular oral capsules, made up of a biocompatible case and have electronic circuitry and mechanisms to capture and transmit images. In addition, robots with diagnostic features such as in vivo body temperature detection and pH monitoring have also been launched in the market. However, a multi-functional unit that will diagnose and cure diseases inside the body has not yet been realized. A remote controlled capsule that will undertake drug delivery and surgical treatment has not been successfully launched in the market. High cost, inadequate power supply, lack of control over drug release, limited space for drug storage on the capsule, inadequate safety and no mechanisms for active locomotion and anchoring have prevented their entry in the market. The capsule robots can revolutionize the current way of diagnosis and treatment. This paper discusses in detail the applications of medical capsule robots in diagnostics, drug delivery and surgical treatment. In diagnostics, detailed analysis has been presented on wireless capsule endoscopes, issues associated with the marketed versions and their corresponding solutions in literature. Moreover, an assessment has been made of the existing state of remote controlled capsules for targeted drug delivery and surgical treatment and their future impact is predicted. Besides the need for multi-functional capsule robots and the areas for further research have also been
Full Text Available Friedrich Ihler, Martin CanisDepartment of Otorhinolaryngology, University Medical Center Göttingen, Göttingen, GermanyAbstract: Ragweed (Ambrosia spp. is an annually flowering plant whose pollen bears high allergenic potential. Ragweed-induced allergic rhinoconjunctivitis has long been seen as a major immunologic condition in Northern America with high exposure and sensitization rates in the general population. The invasive occurrence of ragweed (A. artemisiifolia poses an increasing challenge to public health in Europe and Asia as well. Possible explanations for its worldwide spread are climate change and urbanization, as well as pollen transport over long distances by globalized traffic and winds. Due to the increasing disease burden worldwide, and to the lack of a current and comprehensive overview, this study aims to review the current and emerging treatment options for ragweed-induced rhinoconjunctivitis. Sound clinical evidence is present for the symptomatic treatment of ragweed-induced allergic rhinoconjunctivitis with oral third-generation H1-antihistamines and leukotriene antagonists. The topical application of glucocorticoids has also been efficient in randomized controlled clinical trials. Combined approaches employing multiple agents are common. The mainstay of causal treatment to date, especially in Northern America, is subcutaneous immunotherapy with the focus on the major allergen, Amb a 1. Beyond this, growing evidence from several geographical regions documents the benefit of sublingual immunotherapy. Future treatment options promise more specific symptomatic treatment and fewer side effects during causal therapy. Novel antihistamines for symptomatic treatment are aimed at the histamine H3-receptor. New adjuvants with toll-like receptor 4 activity or the application of the monoclonal anti-immunoglobulin E antibody, omalizumab, are supposed to enhance conventional immunotherapy. An approach targeting toll-like receptor 9 by
Parikh, Raj; Kadowitz, Philip J
Angina pectoris is the consequence of an inequality between the demand and supply of blood to the heart. Angina manifests itself as chest pain or discomfort and is a common complaint of patients in the hospital and in the clinic. There are, in fact, roughly half a million new cases of angina per year. Chest pain, while having many etiologies, is generally considered to be most lethal when related to a cardiac cause. In this review, the authors outline the current medical and surgical therapies that are used in the management of angina. Highlights of the various clinical trials that have assisted in the investigation of these therapies are summarized also. Then, the authors provide a focused review of the novel therapy options for angina that are currently being explored. From new medical treatments to revised surgical techniques to the discovery of stem cell therapy, many innovative options are being investigated for the treatment of angina.
Maffezzoni, Filippo; Formenti, Anna Maria; Mazziotti, Gherardo; Frara, Stefano; Giustina, Andrea
Acromegaly is a relatively rare condition of growth hormone (GH) excess associated with significant morbidity and, when left untreated, high mortality. Therapy for acromegaly is targeted at decreasing GH and insulin-like growth hormone 1 levels, ameliorating patients' symptoms and decreasing any local compressive effects of the pituitary adenoma. The therapeutic options for acromegaly include surgery, medical therapies (such as dopamine agonists, somatostatin receptor ligands and the GH receptor antagonist pegvisomant) and radiotherapy. However, despite all these treatments option, approximately 50% of patients are not adequately controlled. In this paper, the authors discuss: 1) efficacy and safety of current medical therapy 2) the efficacy and safety of the new multireceptor-targeted somatostatin ligand pasireotide 3) medical treatments currently under clinical investigation (oral octreotide, ITF2984, ATL1103), and 4) preliminary data on the use of new injectable and transdermal/transmucosal formulations of octreotide. This expert opinion supports the need for new therapeutic agents and modalities for patients with acromegaly.
O'Brien, Eoin; Dolan, Eamon
This purpose of this article is to review the current recommendations for ambulatory blood pressure measurement (ABPM) and the use of ABPM in assessing treatment. We review current international guidelines and undertake a critical review of evidence supporting the clinical use of ABPM in effectively managing antihypertensive drug treatment. Current guidelines emphasize the diagnostic superiority of ABPM, mainly from the ability of the technique to identify sustained hypertension by allowing for the exclusion of white-coat hypertension and by demonstrating the presence of masked hypertension. ABPM also offers diagnostic insights into nocturnal patterns of blood pressure, such as dipping and nondipping, reverse dipping, and excessive dipping, and the presence of nocturnal hypertension; although less attention is given to the nocturnal behavior of blood pressure in clinical practice, the nocturnal patterns of blood pressure have particular relevance in assessing the response to blood pressure-lowering medication. Surprisingly, although the current guidelines give detailed recommendations on the diagnostic potential and use of ABPM, there are scant recommendations on the benefits and application of the technique for the initiation of blood pressure-lowering therapy in clinical practice and virtually no recommendations on how it might be used to assess the efficacy of drug treatment. In view of a deficiency in the literature on the role of ABPM in assess the efficacy of drug treatment, we put forward proposals to correct this deficiency and guide the prescribing physician on the most appropriate drug administration and dosage over time. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.
A review is given of the current status of quality assurance of treatment planning systems. At this moment only one comprehensive report is available. In order to review national activities a questionnaire has been distributed amongst national societies of medical physicists. From the 23 responding countries, 8 indicated that only limited efforts are underway, 8 answered that a working group is evaluating their specific national requirements while in 5 countries a document is drafted. The highlights of these reports have been summarized. (author)
This article describes topical therapies and treatment guidelines for psoriasis and is based on a presentation given by the authors at a satellite symposium held during the 19th Congress of the European Academy of Dermatology and Venereology, 6-10 October, 2010, in Gothenburg, Sweden. The highly variable nature of psoriasis and its individual presentation in patients can make it difficult to choose the most appropriate treatment. There are many treatment options, from topical treatment with emollients for very mild psoriasis, to systemic therapy with fumaric acid esters, methotrexate or biologics for severe disease. For the treatment of mild-to-moderate psoriasis, topical therapy is generally the most appropriate and a variety of options, both historical and recent, are available. Newer therapies offer greater convenience and fewer side-effects. Of the more recently available therapies, vitamin D analogues and topical corticosteroids are the two with the greatest proven efficacy in randomized clinical trials. A recent Cochrane review showed the highest efficacy overall with the fixed combination vitamin D analogue (calcipotriol) and corticosteroid (betamethasone dipropionate). Indeed, clinical trials have shown that two-compound calcipotriol\\/betamethasone dipropionate ointment has higher efficacy than calcipotriol or betamethasone dipropionate alone. With regard to safety, two-compound calcipotriol\\/betamethasone dipropionate was shown to be suitable for intermittent long-term treatment of mild-to-moderate psoriasis. The findings of the Cochrane review are reflected in the current treatment guidelines from the USA and Germany regarding the treatment of mild-to-moderate psoriasis. In both these guidelines, which will be discussed in this article, the recommended treatments for this patient group are vitamin D analogues and corticosteroids, particularly when used in combination.
This article describes topical therapies and treatment guidelines for psoriasis and is based on a presentation given by the authors at a satellite symposium held during the 19th Congress of the European Academy of Dermatology and Venereology, 6-10 October, 2010, in Gothenburg, Sweden. The highly variable nature of psoriasis and its individual presentation in patients can make it difficult to choose the most appropriate treatment. There are many treatment options, from topical treatment with emollients for very mild psoriasis, to systemic therapy with fumaric acid esters, methotrexate or biologics for severe disease. For the treatment of mild-to-moderate psoriasis, topical therapy is generally the most appropriate and a variety of options, both historical and recent, are available. Newer therapies offer greater convenience and fewer side-effects. Of the more recently available therapies, vitamin D analogues and topical corticosteroids are the two with the greatest proven efficacy in randomized clinical trials. A recent Cochrane review showed the highest efficacy overall with the fixed combination vitamin D analogue (calcipotriol) and corticosteroid (betamethasone dipropionate). Indeed, clinical trials have shown that two-compound calcipotriol\\/betamethasone dipropionate ointment has higher efficacy than calcipotriol or betamethasone dipropionate alone. With regard to safety, two-compound calcipotriol\\/betamethasone dipropionate was shown to be suitable for intermittent long-term treatment of mild-to-moderate psoriasis. The findings of the Cochrane review are reflected in the current treatment guidelines from the USA and Germany regarding the treatment of mild-to-moderate psoriasis. In both these guidelines, which will be discussed in this article, the recommended treatments for this patient group are vitamin D analogues and corticosteroids, particularly when used in combination.
Full Text Available Daniel E Spratt, Nancy LeeDepartment of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USAAbstract: In this article, we focus on the current and emerging treatments in nasopharyngeal cancer (NPC. A detailed evolution of the current standard of care, and new techniques and treatment options will be reviewed. Intergroup 0099 established the role for chemoradiotherapy (chemo-RT in the treatment of nasopharyngeal carcinoma. Multiple randomized Phase III trials have shown the benefit of chemo-RT; however, none of these studies utilized modern radiotherapy (RT techniques of intensity-modulated radiation therapy (IMRT. IMRT has the ability to deliver high doses of radiation to the target structures while sparing adjacent bystander healthy tissues, and has now become the preferred RT treatment modality. Chemotherapy also has had a shifting paradigm of induction and/or adjuvant chemotherapy combined with RT alone, to the investigation with concurrent chemo-RT. New treatment options including targeted monoclonal antibodies and small molecule tyrosine kinase inhibitors are being studied in NPC. These new biologic therapies have promising in vitro activity for NPC, and emerging clinical studies are beginning to define their role. RT continues to expand its capabilities, and since IMRT and particle therapy, specifically intensity-modulated proton therapy (IMPT, has reports of impressive dosimetric efficacy in-silica. Adaptive RT is attempting to reduce toxicity while maintaining treatment efficacy, and the clinical results are still in their youth. Lastly, Epstein–Barr virus (EBV DNA has recently been studied for prediction of tumor response and its use as a biomarker is increasingly promising to aid in early detection as well as supplementing the current staging system. RT with or without chemotherapy remains the standard of care for nasopharyngeal carcinoma. Advances in RT technique, timing of chemotherapy, biologically
LIU, LIN; LU, HONGWEN; LIU, YANG; LIU, CHANGSHAN; XUN, CHU
The aim of the present study was to monitor long term antithyroid drug treatments and to identify prognostic factors for Graves' disease (GD). A total of 306 patients with GD who were referred to the Endocrinology Clinic at Weifang People's Hospital (Weifang, China) between August 2005 and June 2009 and treated with methimazole were included in the present study. Following treatment, patients were divided into non-remission, including recurrence and constant treatment subgroups, and remission groups. Various prognosis factors were analyzed and compared, including: Patient age, gender, size of thyroid prior to and following treatment, thyroid hormone levels, disease relapse, hypothyroidism and drug side-effects, and states of thyrotropin suppression were observed at 3, 6 and 12 months post-treatment. Sixty-five patients (21.2%) were male, and 241 patients (78.8%) were female. The mean age was 42±11 years, and the follow-up was 31.5±6.8 months. Following long-term treatment, 141 patients (46%) demonstrated remission of hyperthyroidism with a mean duration of 18.7±1.9 months. The average age at diagnosis was 45.6±10.3 years in the remission group, as compared with 36.4±8.8 years in the non-remission group (t=3.152; P=0.002). Free thyroxine (FT)3 levels were demonstrated to be 25.2±8.9 and 18.7±9.4 pmol/l in the non-remission and remission groups, respectively (t=3.326, P=0.001). The FT3/FT4 ratio and thyrotrophin receptor antibody (TRAb) levels were both significantly higher in the non-remission group (t=3.331, 3.389, P=0.001), as compared with the remission group. Logistic regression analysis demonstrated that elevated thyroid size, FT3/FT4 ratio and TRAb at diagnosis were associated with poor outcomes. The ratio of continued thyrotropin suppression in the recurrent subgroup was significantly increased, as compared with the remission group (P=0.001), as thyroid function reached euthyroid state at 3, 6 and 12 months post-treatment. Patients with GD exhibiting
Chuah, Seng-Kee; Chiu, Chien-Hua; Tai, Wei-Chen; Lee, Jyong-Hong; Lu, Hung-I; Changchien, Chi-Sin; Tseng, Ping-Huei; Wu, Keng-Liang
Recent advances in the treatment of achalasia include the use of high-resolution manometry to predict the outcome of patients and the introduction of peroral endoscopic myotomy (POEM). The first multicenter randomized, controlled, 2-year follow-up study conducted by the European Achalasia Trial group indicated that laparoscopic Heller myotomy (LHM) was not superior to pneumatic dilations (PD). Publications on the long-term success of laparoscopic surgery continue to emerge. In addition, laparoscopic single-site surgery is applicable to advanced laparoscopic operations such as LHM and anterior fundoplication. The optimal treatment option is an ongoing matter of debate. In this review, we provide an update of the current progress in the treatment of esophageal achalasia. Unless new conclusive data prove otherwise, LHM is considered the most durable treatment for achalasia at the expense of increased reflux-associated complications. However, PD is the first choice for non-surgical treatment and is more cost-effective. Repeated PD according to an "on-demand" strategy based on symptom recurrence can achieve long-term remission. Decision making should be based on clinical evidence that identifies a subcategory of patients who would benefit from specific treatment options. POEM has shown promise but its long-term efficacy and safety need to be assessed further.
Full Text Available Nonsteroidal anti-inflammatory drugs are widely used in pediatric practice for the treatment of fever. The choice of the drug from this group must be based on high effectiveness of medication and the lowest risk of adverse events. Only paracetamol and ibuprofen completely fulfill these requirements at the present times. They are officially recommended by WHO for the use as an anti-fever pediatric medication. The article examines advantages of ibuprofen compared to paracetamol on the basis of results of randomized studies. Author describes a safety of ibuprofen and opportunities of combined treatment with ibuprofen and paracetamol.Key words: children, fever, ibuprofen, paracetamol, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(2:156-160
Full Text Available This article reviews the mechanism, symptoms, causes, severity, diagnosis, prevention and present recommendations for surgical as well as non-surgical management of pressure ulcers. Particular focus has been placed on the current understandings and the newer modalities for the treatment of pressure ulcers. The paper also covers the role of nutrition and pressure-release devices such as cushions and mattresses as a part of the treatment algorithm for preventing and quick healing process of these wounds. Pressure ulcers develop primarily from pressure and shear; are progressive in nature and most frequently found in bedridden, chair bound or immobile people. They often develop in people who have been hospitalised for a long time generally for a different problem and increase the overall time as well as cost of hospitalisation that have detrimental effects on patient′s quality of life. Loss of sensation compounds the problem manifold, and failure of reactive hyperaemia cycle of the pressure prone area remains the most important aetiopathology. Pressure ulcers are largely preventable in nature, and their management depends on their severity. The available literature about severity of pressure ulcers, their classification and medical care protocols have been described in this paper. The present treatment options include various approaches of cleaning the wound, debridement, optimised dressings, role of antibiotics and reconstructive surgery. The newer treatment options such as negative pressure wound therapy, hyperbaric oxygen therapy, cell therapy have been discussed, and the advantages and disadvantages of current and newer methods have also been described.
Bhattacharya, Surajit; Mishra, R. K.
This article reviews the mechanism, symptoms, causes, severity, diagnosis, prevention and present recommendations for surgical as well as non-surgical management of pressure ulcers. Particular focus has been placed on the current understandings and the newer modalities for the treatment of pressure ulcers. The paper also covers the role of nutrition and pressure-release devices such as cushions and mattresses as a part of the treatment algorithm for preventing and quick healing process of these wounds. Pressure ulcers develop primarily from pressure and shear; are progressive in nature and most frequently found in bedridden, chair bound or immobile people. They often develop in people who have been hospitalised for a long time generally for a different problem and increase the overall time as well as cost of hospitalisation that have detrimental effects on patient's quality of life. Loss of sensation compounds the problem manifold, and failure of reactive hyperaemia cycle of the pressure prone area remains the most important aetiopathology. Pressure ulcers are largely preventable in nature, and their management depends on their severity. The available literature about severity of pressure ulcers, their classification and medical care protocols have been described in this paper. The present treatment options include various approaches of cleaning the wound, debridement, optimised dressings, role of antibiotics and reconstructive surgery. The newer treatment options such as negative pressure wound therapy, hyperbaric oxygen therapy, cell therapy have been discussed, and the advantages and disadvantages of current and newer methods have also been described. PMID:25991879
Taviloğlu, Korhan; Aydin, Erol; Ertekin, Cemalettin; Güloğlu, Recep; Kurtoğlu, Mehmet
Our aim was to emphasize the role of endoscopic detorsion in the treatment of sigmoid colon volvulus, which we currently apply in the majority of our cases. The data of 37 patients were analyzed in a retrospective manner, during a 86-month period, between May 1994 and July 2001. The patients were classified into three groups. The first group consisted of 9 patients with resection and anastomosis, the second group consisted of 20 patients with Hartmann's procedure, and the third group consisted of 8 patients with endoscopic detorsion. Complications were encountered in 7 patients (19%), and 3 patients (8%) died following treatment. We favor colonic resection following endoscopic treatment. Resection should be preferred, if endoscopic detorsion is not successful or in the presence of a complication.
... 21 Food and Drugs 9 2010-04-01 2010-04-01 false May the Office of National Drug Control Policy exclude a person who is not currently participating in a nonprocurement transaction? 1404.135 Section 1404.135 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) General § 1404.135 May the...
Bentley, G; Dowd, G
Chondromalacia patellae is a distinct clinical entity characterized by retropatellar pain that is associated with recognizable changes in the articular cartilage of the posterior surface of the patella. Several factors may be involved in the etiology, such as severe patella alta, trauma, and, in rare cases, abnormal patellar tracking. Clinical symptoms and signs are reliable in only 50% of cases, but measurable quadriceps wasting, palpable patellofemoral crepitus, and effusion are strongly suggestive. Diagnosis must be confirmed by arthroscopy or direct examination of the posterior surface of the patella. Radiologic measurements of patellofemoral relations are of limited value in diagnosis. The initial pathologic finding is usually surface cartilage breakdown. Radioisotope studies show cartilage cell replication which suggests a healing capacity in early cases following treatment that alters the load through the affected cartilage. There is no evidence of progression to patellofemoral osteoarthritis, which is probably a different entity. The treatment should be conservative where possible with isometric quadriceps exercises and simple anti-inflammatory drugs such as aspirin. Operative treatment is indicated for patients with persistent pain and macroscopic involvement of more than half a centimeter of the articular cartilage surface. The simplest effective procedure that avoids quadriceps dysfunction and fibrosis is a distal patellar tendon medial realignment with lateral release and medial reefing of the quadriceps expansion. Patellectomy is indicated in more extensive involvement of the patella of 2 or more centimeters in diameter, but this must be performed only when the patient has excellent quadriceps function before surgery and is motivated to exercise after surgery.
Monti, Elena; Mottes, Monica; Fraschini, Paolo; Brunelli, PierCarlo; Forlino, Antonella; Venturi, Giacomo; Doro, Francesco; Perlini, Silvia; Cavarzere, Paolo; Antoniazzi, Franco
Osteogenesis imperfecta (OI) is the most common bone genetic disorder and it is characterized by bone brittleness and various degrees of growth disorder. Clinical severity varies widely; nowadays eight types are distinguished and two new forms have been recently described although not yet classified. The approach to such a variable and heterogeneous disease should be global and therefore multidisciplinary. For simplicity, the objectives of treatment can be reduced to three typical situations: the lethal perinatal form (type II), in which the problem is survival at birth; the severe and moderate forms (types III–IX), in which the objective is ‘autonomy’; and the mild form (type I), in which the aim is to reach ‘normal life’. Three types of treatment are available: non-surgical management (physical therapy, rehabilitation, bracing and splinting), surgical management (intramedullary rod positioning, spinal and basilar impression surgery) and medical-pharmacological management (drugs to increase the strength of bone and decrease the number of fractures as bisphosphonates or growth hormone, depending on the type of OI). Suggestions and guidelines for a therapeutic approach are indicated and updated with the most recent findings in OI diagnosis and treatment. PMID:20856683
Beitel, Mark; Oberleitner, Lindsay; Muthulingam, Dharushana; Oberleitner, David; Madden, Lynn M; Marcus, Ruthanne; Eller, Anthony; Bono, Madeline H; Barry, Declan T
Little is known about possible experiences of burnout among drug counselors in opioid treatment programs that are scaling up capacity to address the current opioid treatment gap. Participants in this quality improvement study were 31 drug counselors employed by large opioid treatment programs whose treatment capacities were expanding. Experiences of burnout and approaches for managing and/or preventing burnout were examined using individual semi-structured interviews, which were audiotaped, transcribed, and systematically coded by a multidisciplinary team using grounded theory. Rates of reported burnout (in response to an open-ended question) were lower than expected, with approximately 26% of participants reporting burnout. Counselor descriptions of burnout included cognitive, affective, behavioral, and physiological symptoms; and job-related demands were identified as a frequent cause. Participants described both self-initiated (e.g., engaging in pleasurable activities, exercising, taking breaks during workday) and system-supported strategies for managing or preventing burnout (e.g., availing of supervision and paid time off). Counselors provided recommendations for system-level changes to attenuate counselor risk of burnout (e.g., increased staff-wide encounters, improved communication, accessible paid time off, and increased clinical supervision). Findings suggest that drug counselor burnout is not inevitable, even in opioid treatment program settings whose treatment capacities are expanding. Organizations might benefit from routinely assessing counselor feedback about burnout and implementing feasible recommendations to attenuate burnout and promote work engagement.
... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Community Transitional Drug Abuse... JUSTICE INSTITUTIONAL MANAGEMENT DRUG PROGRAMS Drug Abuse Treatment Program § 550.56 Community Transitional Drug Abuse Treatment Program (TDAT). (a) For inmates to successfully complete all components of...
Gómez, Ricardo; Caballero, Ricardo; Barana, Adriana; Amorós, Irene; De Palm, Sue-Haida; Matamoros, Marcos; Núñez, Mercedes; Pérez-Hernández, Marta; Iriepa, Isabel; Tamargo, Juan; Delpón, Eva
We hypothesize that some drugs, besides flecainide, increase the inward rectifier current (IK1) generated by Kir2.1 homotetramers (IKir2.1) and thus, exhibit pro- and/or antiarrhythmic effects particularly at the ventricular level. To test this hypothesis, we analysed the effects of propafenone, atenolol, dronedarone, and timolol on Kir2.x channels. Currents were recorded with the patch-clamp technique using whole-cell, inside-out, and cell-attached configurations. Propafenone (0.1 nM-1 µM) did not modify either IK1 recorded in human right atrial myocytes or the current generated by homo- or heterotetramers of Kir2.2 and 2.3 channels recorded in transiently transfected Chinese hamster ovary cells. On the other hand, propafenone increased IKir2.1 (EC50 = 12.0 ± 3.0 nM) as a consequence of its interaction with Cys311, an effect which decreased inward rectification of the current. Propafenone significantly increased mean open time and opening frequency at all the voltages tested, resulting in a significant increase of the mean open probability of the channel. Timolol, which interacted with Cys311, was also able to increase IKir2.1. On the contrary, neither atenolol nor dronedarone modified IKir2.1. Molecular modelling of the Kir2.1-drugs interaction allowed identification of the pharmacophore of drugs that increase IKir2.1. Kir2.1 channels exhibit a binding site determined by Cys311 that is responsible for drug-induced IKir2.1 increase. Drug binding decreases channel affinity for polyamines and current rectification, and can be a mechanism of drug-induced pro- and antiarrhythmic effects not considered until now. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: email@example.com.
Full Text Available Introduction: Obesity is a worldwide health problem whose prevalence is on the increase. Many obesity-associated diseases require intensive medical treatment and are the cause of a large proportion of health-related expenditures in Germany. Treatment of obesity includes nutritional, exercise and behaviour therapy, usually in combination. The goal of behaviour therapy for obesity is to bring about a long-term alteration in the eating and exercise habits of overweight and obese individuals. Under certain circumstances, drug treatment may be indicated. Objectives: What is the effectiveness of behaviour therapy for obesity considering approved drugs reduce weight under medical, economic, ethical-social and legal aspects? Methods: A systematic review was conducted using relevant electronic literature databases. Publications chosen according to predefined criteria are evaluated by approved methodical standards of the evidence-based medicine systematically and qualitatively. Results: In total 18 studies, included one HTA and one meta-analysis could be identified according to the predefined inclusion criteria. Three studies compare behaviour therapy to other therapy forms (advice or instruction on nutritional changes, physical activity or a combination of the two, six studies evaluate different forms of behaviour therapy, four studies and four studies compare behaviour therapies mediated by Internet or telephone. Three studies could be identified examining the effect of the combination of behaviour and drug therapy. Furthermore one HTA and one meta-analysis could be included in the evaluation. The behaviour therapy in comparison with other therapy forms reveals a higher effectiveness. In comparison of the different therapeutic approaches of the behaviour therapy intensive behaviour therapy forms and group therapy show a higher effectiveness. Studies related to behaviour therapy based on media support demonstrate a weight reduction both through the
YU. N. Perlamutrov
Full Text Available Actuality. High incidence of atopic dermatitis and its association with systemic pathology determine the need of broad treatment options on the base of the modern data on pathophysiology of the disease. Aim of the study. Analysis of the clinical efficacy of the complex therapy with application drug Kestine® and probiotic FlorOK. Materials and Methods of the study. 55 patients with atopic dermatitis with mild and medium severity stages were examined and treated. The SCORAD Index and the Prurindex were used for assessment of AD severity; H2- test was used for evaluation of the digestive system function. Study results. It was stated high clinical efficacy of the complex therapy with application drug Kestine® and probiotic FlorOK accompanied by fast arrest of the itch.
Mahan, Charles E
Target specific anticoagulants (TSOACs) have recently been introduced to the US market for multiple indications including venous thromboembolism (VTE) prevention in total hip and knee replacement surgeries, VTE treatment and reduction in the risk of stroke in patients with non-valvular atrial fibrillation (NVAF). Currently, three TSOACs are available including rivaroxaban, apixaban, and dabigatran with edoxaban currently under Food and Drug Administration review for VTE treatment and stroke prevention in NVAF. The introduction of these agents has created a paradigm shift in anticoagulation by considerably simplifying treatment and anticoagulant initiation for patients by giving clinicians the opportunity to use a rapid onset, rapid offset, oral agent. The availability of these rapid onset TSOACs is allowing for outpatient treatment of low risk pulmonary embolism and deep vein thrombosis which can greatly reduce healthcare costs by avoiding inpatient hospitalizations and treatment for the disease. Additionally with this practice, the complications of an inpatient hospitalization may also be avoided such as nosocomial infections. Single-agent approaches with TSOACs represent a paradigm shift in the treatment of VTE versus the complicated overlap of a parenteral agent with warfarin. Transitions between anticoagulants, including TSOACs, are a high-risk period for the patient, and clinicians must carefully consider patient characteristics such as renal function as well as the agents that are being transitioned. TSOAC use appears to be growing slowly with improved payment coverage throughout the US.
Full Text Available Cancer incidence and mortality depend on a number of factors, including age, socio-economic status and geographical location, and its prevalence is growing around the world. Most of cancer treatments include external beam radiotherapy or brachytherapy. Brachytherapy, a type of radiotherapy with energy from radionuclides inserted directly into the tumor, is increasingly used in cancer treatment. For cervical and skin cancers, it has become a standard therapy for more than 100 years as well as an important part of the treatment guidelines for other malignancies, including head and neck, skin, breast, and prostate cancers. Compared to external beam radiotherapy, brachytherapy has the potential to deliver an ablative radiation dose over a short period of time directly to the altered tissue area with the advantage of a rapid fall-off in dose, and consequently, sparing of adjacent organs. As a result, the patient is able to complete the treatment earlier, and the risks of occurrence of another cancer are lower than in conventional radiotherapy treatment. Brachytherapy has increased its use as a radical or palliative treatment, and become more advanced with the spread of pulsed-dose-rate and high-dose-rate afterloading machines; the use of new 3D/4D planning systems has additionally improved the quality of the treatment. The aim of the present study was to present short summaries of current studies on brachytherapy for the most frequently diagnosed tumors. Data presented in this manuscript should help especially young physicians or physicists to explore and introduce brachytherapy in cancer treatments.
Wildy, K S; Wasko, M C
Treating patients with osteoarthritis (OA) and rheumatoid arthritis (RA) remains challenging; however, new agents offer the chance for an improved quality of life. As an alternative to traditional nonsteroidal anti-inflammatories, cyclooxygenase-2 inhibitors provide pain relief for OA and RA patients with possible fewer side effects. Otherwise, OA patients may opt for topical agents, injections, or supplements. Rheumatoid arthritis research has led to an improved understanding of the inflammatory cascade and an appreciation of the early tissue destruction. A new treatment philosophy has thus emerged along with the development of new biologic agents; the latter, along with combination therapy and a new disease modifying antirheumatic drug, leflunomide, have greatly expanded the chances for disease control in RA patients.
...] Draft Guidance for Industry on Pulmonary Tuberculosis: Developing Drugs for Treatment; Availability...) is announcing the availability of a draft guidance for industry entitled ``Pulmonary Tuberculosis... of antimycobacterial drugs for the treatment of pulmonary tuberculosis. This guidance applies to the...
Ritter, Alison; Hull, Philip; Berends, Lynda; Chalmers, Jenny; Lancaster, Kari
The aim of this study was to establish a conceptual schema for government purchasing of alcohol and other drug treatment in Australia which could encompass the diversity and variety in purchasing arrangements, and facilitate better decision-maker by purchasers. There is a limited evidence base on purchasing arrangements in alcohol and drug treatment despite the clear impact of purchasing arrangements on both treatment processes and treatment outcomes. The relevant health and social welfare literature on purchasing arrangements was reviewed; data were collected from Australian purchasers and providers of treatment giving detailed descriptions of the array of purchasing arrangements. Combined analysis of the literature and the Australian purchasing data resulted in a draft schema which was then reviewed by an expert committee and subsequently finalised. The conceptual schema presented here was purpose-built for alcohol and other drug treatment, with its overlap between health and social welfare services. It has three dimensions: 1. The ways in which providers are chosen; 2. The ways in which services are paid for; and 3. How price is managed. Distinguishing between the methods for choosing providers (such as competitive or individually negotiated processes) from the way in which organisations are paid for their provision of treatment (such as via a block grant or payment for activity) provides conceptual clarity and enables closer analysis of each mechanism. Governments can improve health and wellbeing by making informed decisions about the way they purchase and fund alcohol and other drug treatment. Research comparing different purchasing arrangements can provide a vital evidence-base to inform funders; however a first step is to accurately and consistently categorise current approaches against a typology or conceptual schema. Copyright © 2016 Elsevier Ltd. All rights reserved.
Yadav, Meena K; Short, Michael D; Aryal, Rupak; Gerber, Cobus; van den Akker, Ben; Saint, Christopher P
This review critically evaluates the types and concentrations of key illicit drugs (cocaine, amphetamines, cannabinoids, opioids and their metabolites) found in wastewater, surface water and drinking water sources worldwide and what is known on the effectiveness of wastewater treatment in removing such compounds. It is also important to amass information on the trends in specific drug use as well as the sources of such compounds that enter the environment and we review current international knowledge on this. There are regional differences in the types and quantities of illicit drug consumption and this is reflected in the quantities detected in water. Generally, the levels of illicit drugs in wastewater effluents are lower than in raw influent, indicating that the majority of compounds can be at least partially removed by conventional treatment processes such as activated sludge or trickling filters. However, the literature also indicates that it is too simplistic to assume non-detection equates to drug removal and/or mitigation of associated risks, as there is evidence that some compounds may avoid detection via inadequate sampling and/or analysis protocols, or through conversion to transformation products. Partitioning of drugs from the water to the solids fraction (sludge/biosolids) may also simply shift the potential risk burden to a different environmental compartment and the review found no information on drug stability and persistence in biosolids. Generally speaking, activated sludge-type processes appear to offer better removal efficacy across a range of substances, but the lack of detail in many studies makes it difficult to comment on the most effective process configurations and operations. There is also a paucity of information on the removal effectiveness of alternative treatment processes. Research is also required on natural removal processes in both water and sediments that may over time facilitate further removal of these compounds in receiving
Brandt-Christensen, M; Lopez, A G; Nilsson, F M
OBJECTIVE: To estimate the rate of treatment with anti-parkinson drugs (APD) among patients with depression. METHOD: In a nationwide case register linkage study, all persons with a main diagnosis of depression during 5 years were identified. A control group of persons with diagnoses of osteoarthr...... that prescription of APD reflects the presence of Parkinson's disease, results support a positive statistical association between depressive disorders and Parkinson's disease.......OBJECTIVE: To estimate the rate of treatment with anti-parkinson drugs (APD) among patients with depression. METHOD: In a nationwide case register linkage study, all persons with a main diagnosis of depression during 5 years were identified. A control group of persons with diagnoses...... of osteoarthritis was included. The subsequent risk of getting treatment with APD was estimated for the two groups. Statistical analyses involved Poisson's regression and competing risk models. RESULTS: A total of 14 991 persons were included. The rate of getting APD was 2.57 (95% CI: 1.46-4.52) times higher...
Full Text Available Novel drugs, drug sequences and combinations have improved the outcome of prostate cancer in recent years. The latest approvals include abiraterone acetate, enzalutamide and apalutamide which target androgen receptor (AR signaling, radium-223 dichloride for reduction of bone metastases, sipuleucel-T immunotherapy and taxane-based chemotherapy. Adding abiraterone acetate to androgen deprivation therapy (ADT in order to achieve complete androgen blockade has proven highly beneficial for treatment of locally advanced prostate cancer and metastatic hormone-sensitive prostate cancer (mHSPC. Also, ADT together with docetaxel treatment showed significant benefit in mHSPC. Ongoing clinical trials for different subgroups of prostate cancer patients include the evaluation of the second-generation AR antagonists enzalutamide, apalutamide and darolutamide, of inhibitors of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K pathway, of inhibitors of DNA damage response, of targeted alpha therapy and of prostate-specific membrane antigen (PSMA targeting approaches. Advanced clinical studies with immune checkpoint inhibitors have shown limited benefits in prostate cancer and more trials are needed to demonstrate efficacy. The identification of improved, personalized treatments will be much supported by the major progress recently made in the molecular characterization of early- and late-stage prostate cancer using “omics” technologies. This has already led to novel classifications of prostate tumors based on gene expression profiles and mutation status, and should greatly help in the choice of novel targeted therapies best tailored to the needs of patients.
Uchiyama, Makoto; Konno, Michiko
Pharmacological treatments of insomnia have become safer since the first benzodiazepine receptor agonist (BzRA) hypnotic was introduced in the 1960's. Though BzRAs could hardly cause a fatal condition even in cases of overdosing, they had inherited the arguments on addiction and withdrawal from the prior studies of barbiturate hypnotics that indicated they are strongly addictive. In the 2000s, it was repeatedly demonstrated that insomnia as well as sleep deprivation underlie the development and deterioration of comorbid diseases such as hypertension, cardiovascular diseases, diabetes and depression, and that the proper use of hypnotic drugs is unlikely to cause tolerance, addiction nor rebound phenomena, but likely to be associated with improvement of QOL. Thus, the 2005's consensus report on chronic insomnia by NIH has recommended general physicians to facilitate insomnia treatment to prevent the development of physical and/or mental disorders. The author reviewed in this article the efficacy and side effects of BzRA hypnotics, a hypnotic drug therapy combined with cognitive and behavioral interventions, uses of melatonin receptor agonist in general and sleep medicine practices, and future utilization of newly-developed orexin antagonists for insomnia treatment.
Vannemreddy, Prasad; Slavin, Konstantin V
Spinal cord stimulation (SCS) is thought to relieve chronic intractable pain by stimulating nerve fibers in the spinal cord. The resulting impulses in the fibers may inhibit the conduction of pain signals to the brain, according to the pain gate theory proposed by Melzack and Wall in 1965 and the sensation of pain is thus blocked. Although SCS may reduce pain, it will not eliminate it. After a period of concern about safety and efficacy, SCS is now regaining popularity among pain specialists for the treatment of chronic pain. The sympatholytic effect of SCS is one of its most interesting therapeutic properties. This effect is considered responsible for the effectiveness of SCS in peripheral ischemia, and at least some cases of complex regional pain syndrome. The sympatholytic effect has also been considered part of the management of other chronic pain states such as failed back surgery syndrome, phantom pain, diabetic neuropathy, and postherpetic neuralgia. In general, SCS is part of an overall treatment strategy and is used only after the more conservative treatments have failed. The concept of SCS has evolved rapidly following the technological advances that have produced leads with multiple contact electrodes and battery systems. The current prevalence of patients with chronic pain requiring treatment other than conventional medical management has significantly increased and so has been the need for SCS. With the cost benefit analysis showing significant support for SCS, it may be appropriate to offer this as an effective alternative treatment for these patients.
Full Text Available Ahmet Gokce, Julie C Wang, Mary K Powers, Wayne JG HellstromDepartment of Urology, Tulane University – School of Medicine, New Orleans, LA, USAAbstract: Peyronie's disease (PD is a condition of the penis, characterized by the presence of localized fibrotic plaque in the tunica albuginea. PD is not an uncommon disorder, with recent epidemiologic studies documenting a prevalence of 3–9% of adult men affected. The actual prevalence of PD may be even higher. It is often associated with penile pain, anatomical deformities in the erect penis, and difficulty with intromission. As the definitive pathophysiology of PD has not been completely elucidated, further basic research is required to make progress in the understanding of this enigmatic condition. Similarly, research on effective therapies is limited. Currently, nonsurgical treatments are used for those men who are in the acute stage of PD, whereas surgical options are reserved for men with established PD who cannot successfully penetrate. Intralesional treatments are growing in clinical popularity as a minimally invasive approach in the initial treatment of PD. A surgical approach should be considered when men with PD do not respond to conservative, medical, or minimally invasive therapies for approximately 1 year and cannot have satisfactory sexual intercourse. As scientific breakthroughs in the understanding of the mechanisms of this disease process evolve, novel treatments for the many men suffering with PD are anticipated.Keywords: oral therapy, intralesional treatment, topical therapy, extracorporeal shockwave therapy, traction devices, plication, incision and grafting, penile prosthesis.
Full Text Available Objective. To perform an evidence-based review of treatments for Toxoplasma retinochoroiditis (TRC. Methods. A systematic literature search was performed using the PubMed database and the key phrase “ocular toxoplasmosis treatment” and the filter for “controlled clinical trial” and “randomized clinical trial” as well as OVID medline (1946 to May week 2 2014 using the keyword ‘‘ocular toxoplasmosis’’. The included studies were used to evaluate the various treatment modalities of TRC. Results. The electronic search yielded a total of 974 publications of which 44 reported on the treatment of ocular toxoplasmosis. There were 9 randomized controlled studies and an additional 3 comparative studies on the treatment of acute TRC with systemic or intravitreous antibiotics or on reducing the recurrences of TRC. Endpoints of studies included visual acuity improvement, inflammatory response, lesion size changes, recurrences of lesions, and adverse effects of medications. Conclusions. There was conflicting evidence as to the effectiveness of systemic antibiotics for TRC. There is no evidence to support that one antibiotic regimen is superior to another so choice needs to be informed by the safety profile. Intravitreous clindamycin with dexamethasone seems to be as effective as systemic treatments. There is currently level I evidence that intermittent trimethoprim-sulfamethoxazole prevents recurrence of the disease.
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 Edelgard Anna Kaiser,1 Ulrich Lotze,2 Hans Hendrik Schäfer1,31Roche Diagnostics International AG, Rotkreuz, Switzerland; 2Department of Internal Medicine, DRK-Manniske-Krankenhaus Bad Frankenhausen, Bad Frankenhausen, Germany; 3Institute of Anatomy II, University Hospital Jena, Friedrich-Schiller University, Jena, GermanyAbstract: Treatment of hypertension in the elderly is expected to become more complex in the coming decades. Based on the current landscape of clinical trials, guideline recommendations remain inconclusive. The present review discusses the latest evidence derived from studies available in 2013 and investigates optimal blood pressure (BP and preferred treatment substances. Three common archetypes are discussed that hamper the treatment of hypertension in the very elderly. In addition, this paper presents the current recommendations of the NICE 2011, JNC7 2013-update, ESH/ESC 2013, CHEP 2013, JNC8 and ASH/ISH guidelines for elderly patients. Advantages of the six main substance classes, namely diuretics, beta-blockers (BBs, calcium channel blockers (CCBs, angiotensin-converting enzyme inhibitors (ACEIs, angiotensin receptor blockers (ARBs, and direct renin inhibitors (DRIs are discussed. Medical and economic implications of drug administration in the very elderly are presented. Avoidance of treatment-related adverse effects has become increasingly relevant. Current substance classes are equally effective, with similar effects on cardiovascular outcomes. Selection of substances should therefore also be based on collateral advantages of drugs that extend beyond BP reduction. The combination of ACEIs and diuretics appears to be favorable in managing systolic/diastolic hypertension. Diuretics are a preferred and cheap combination drug, and the combination with CCBs is recommended for patients with isolated systolic hypertension. ACEIs and CCBs are favorable for patients with dementia, while CCBs and ARBs imply substantial cost
Arenberger, P; Arenbergerova, M
Actinic keratosis (AK) is a characteristic skin lesion on skin areas of subjects with mainly phototype I and phototype II, or with specific genetic factors and who are exposed to prolonged ultraviolet radiation. AK may be considered a precursor of in situ squamous cell carcinoma (SCC), a type of non-melanoma skin cancer (NMSC). However, it is still not possible to predict which AK lesions will develop into SCC. Early treatment of AK is therefore recommended. Despite the increasing number of patients with AK developing into SCC, to date, there is still no clear suggestion of therapeutic strategy for AK. Current treatment consists of a multitude of topical lesion-directed or field-directed therapies or a combination of both. Recently, orally administered nicotinamide has shown to significantly reduce rates of new NMSC and AK in high-risk patients. This study aims to provide an update on the most relevant information about AK and to provide an insight into current and new treatment options. © 2017 European Academy of Dermatology and Venereology.
Chuang, Tang-Wei; Chen, Shou-Chien; Chen, Kow-Tong
The aim of this study was to explore the recent advances in diagnosis and treatment of gastroesophageal reflux disease (GERD). Previous studies were searched using the terms "gastroesophageal reflux disease" and "diagnosis" or "treatment" in Medline and Pubmed. Articles that were not published in the English language, manuscripts without an abstract, reviews, meta-analysis, and opinion articles were excluded from the review. After a preliminary screening, all of the articles were reviewed and synthesized to provide an overview of the contemporary approaches to GERD. GERD has a variety of symptomatic manifestations, which can be grouped into typical, atypical and extra-esophageal symptoms. Those with the highest specificity for GERD are acid regurgitation and heartburn. In the absence of other alarming symptoms, these symptoms allow one to make a presumptive diagnosis of GERD and initiate empiric therapy. GERD-associated complications include erosive esophagitis, peptic stricture, Barrett's esophagus, esophageal adenocarcinoma and pulmonary disease. Management of GERD may involve lifestyle modifications, medical and surgical therapy. Medical therapy involves acid suppression, which can be achieved with antacids, histamine-receptor antagonists or proton-pump inhibitors. Whereas most patients can be effectively managed with medical therapy, others may go on to require anti-reflux surgery after undergoing a proper pre-operative evaluation. The management of this disease requires a complex approach. Maintenance therapy of GERD after using anti-secretory drugs should be continuously monitored. © Acta Gastro-Enterologica Belgica.
Full Text Available Anticholinergic drugs block muscarinic effect of acetylcholine on the receptors of postjunctional membranes and so inhibit the answer of the postganglionic parasympathetic nerve. The loss of M2 muscarinic receptors function occurs in asthmatics and it contributes to bronchial hyperresponsiveness and it is not a chronic feature of asthma, instead it characterizes asthma exacerbation. The loss of M2 muscarinic receptor function in children and adults happens during antigen bronchoprovocation or during exposition of asthmatics to ozone. After inhalation, ipratropium bromide (IB can be found in a small quantity in circulation and it links less readily to muscarinic receptors on airway smooth muscles as related to its absorption after intravenous application. In the stepwise approach of asthma inhaled anticholinergics is recommended if the symptoms of the disease cannot be adequately controlled by a regular inhalation of antiinflammatory drugs with β2-agonist and oral steroids. The improvement of the airway inspiratory capacity is more elevated than the improvement of FEV1 after inhalation of IB. IB has similar effect as salbutamol and it is recommended to control a stable chronic obstructive disease. During our numerous investigations and up-to-date experience in the usage of 5-7 μg/kg/body mass of IB repeated every 4-6 hours in combination with salbutamol, we did not notice adverse effects of the drug in infants. IB is recommended for hospital treatment of children. .
unnecessary bureaucracy and regulation. As a student of Tom's in the 1970s in London, working on hepatoma-specific alkylating agents at Charing Cross Hospital in collaboration with his lab on the other side of town, I can attest to the fact that the regulatory hurdles to cancer drug development just twenty years later have added immeasurably to the effort and cost of cancer drug development. However, I look with optimism to the future of cancer diagnosis, prevention and treatment. It is a future where what we are learning now about the molecular and genetic basis of cancer will find their clinical outlet just as surely as the anatomic, microbial, metabolic and endocrine basis for disease has in the past. This new knowledge will provide new techniques in molecular diagnosis, which will allow us to predict which in situ cancers are destined for malignant behavior, and which can be safely watched without the need for intervention. Individual patient risk for particular cancers will be accurately predictable, so that patients can alter lifestyle habits or begin other prevention strategies. Oncogenes and growth suppressor genes give us new targets to inhibit or replace. Tumor-specific kinases will meet their inhibitors. The oncologist will play a leading role in understanding, applying and interpreting this new information in the clinic-an exciting and challenging future!
Koskinas, Konstantinos; Wilhelm, Matthias; Windecker, Stephan
Statins are the cornerstone of the management of dyslipidaemias and prevention of cardiovascular disease. Although statins are, overall, safe and well tolerated, adverse events can occur and constitute an important barrier to maintaining long-term adherence to statin treatment. In patients who cannot tolerate statins, alternative treatments include switch to another statin, intermittent-dosage regimens and non-statin lipid-lowering medications. Nonetheless, a high proportion of statin-intolerant patients are unable to achieve recommended low-density lipoprotein (LDL) cholesterol goals, thereby resulting in substantial residual cardiovascular risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protease implicated in LDL receptor degradation and plays a central role in cholesterol metabolism. In recent studies, PCSK9 inhibition by means of monoclonal antibodies achieved LDL cholesterol reductions of 50% to 70% across various patient populations and background lipid-lowering therapies, while maintaining a favourable safety profile. The efficacy and safety of the monoclonal antibodies alirocumab and evolocumab were confirmed in statin-intolerant patients, indicating that PCSK9 inhibitors represent an attractive treatment option in this challenging clinical setting. PCSK9 inhibitors recently received regulatory approval for clinical use and may be considered in properly selected patients according to current consensus documents, including patients with statin intolerance. In this review we summarise current evidence regarding diagnostic evaluation of statin-related adverse events, particularly statin-associated muscle symptoms, and we discuss current recommendations on the management of statin-intolerant patients. In view of emerging evidence of the efficacy and safety of PCSK9 inhibitors, we further discuss the role of monoclonal PCSK9 antibodies in the management of statin-intolerant hypercholesterolaemic patients.
Puri, Ajay; Agarwal, Manish
Giant cell tumor (GCT) of bone though one of the commonest bone tumors encountered by an orthopedic surgeon continues to intrigue treating surgeons. Usually benign, they are locally aggressive and may occasionally undergo malignant transformation. The surgeon needs to strike a balance during treatment between reducing the incidence of local recurrence while preserving maximal function.Differing opinions pertaining to the use of adjuvants for extension of curettage, the relative role of bone graft or cement to pack the defect and the management of recurrent lesions are some of the issues that offer topics for eternal debate.Current literature suggests that intralesional curettage strikes the best balance between controlling disease and preserving optimum function in the majority of the cases though there may be occasions where the extent of the disease mandates resection to ensure adequate disease clearance.An accompanying treatment algorithm helps outline the management strategy in GCT.
Full Text Available Giant cell tumor (GCT of bone though one of the commonest bone tumors encountered by an orthopedic surgeon continues to intrigue treating surgeons. Usually benign, they are locally aggressive and may occasionally undergo malignant transformation. The surgeon needs to strike a balance during treatment between reducing the incidence of local recurrence while preserving maximal function. Differing opinions pertaining to the use of adjuvants for extension of curettage, the relative role of bone graft or cement to pack the defect and the management of recurrent lesions are some of the issues that offer topics for eternal debate. Current literature suggests that intralesional curettage strikes the best balance between controlling disease and preserving optimum function in the majority of the cases though there may be occasions where the extent of the disease mandates resection to ensure adequate disease clearance. An accompanying treatment algorithm helps outline the management strategy in GCT.
Ross, Dana; Schumacher, Joseph E
The purpose of this study was to objectively and quantitatively assess individual skill level of male condom use. This study developed a reliable and face valid assessment of correct male condom use based on Centers for Disease Control and Prevention criteria. Participants (N= 163) were recruited from persons in treatment for cocaine addiction. Condom use was assessed on the basis of correct completion of eight discrete steps. An overall score of 40% correct condom use indicated the need for training in this sample. Assessment showed training needs especially related to steps involving reduction of ejaculate leakage and steps related to potential hazards of nonoxynol-9 use. Frequency of condom use was also assessed; there was no correlation between frequency of condom use and condom use skill. Drug addiction treatment programs are encouraged to incorporate HIV risk reduction programs that teach condom use skills and use the CUDOS as an empirical measure of condom skill acquisition.
McCarty, Dennis; Roman, Paul M; Sorensen, James; Weisner, Constance
Health services research is a multidisciplinary field that examines ways to organize, manage, finance, and deliver high-quality care. This specialty within substance abuse research developed from policy analyses and needs assessments that shaped federal policy and promoted system development in the 1970s. After the authorization of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA), patient information systems supported studies of treatment processes and outcomes. Health services research grew substantially in the 1990s when NIAAA and NIDA moved into the National Institutes of Health and legislation allocated 15% of their research portfolio to services research. The next decade will emphasize research on quality of care, adoption and use of evidence-based practices (including medication), financing reforms and integration of substance abuse treatment with primary care and mental health services.
Full Text Available Azelaic acid (AZA is a naturally occurring substance produced by Malassezia furfur which exerts various effects on the skin. Azelaic acid has antibacterial, anti-inflammatory, keratolytic, comedolytic, sebostatic and tyrosinase-inhibiting properties. Topical application of AZA as 20% cream or 15% gel is a well-established therapeutic method in various common dermatoses, mainly acne vulgaris, rosacea and disorders associated with hyperpigmentation. Azelaic acid is used as a component of chemical peels as well. The paper summarizes the most relevant issues concerning AZA application in dermatological treatment based on current knowledge.
Full Text Available This study was aimed to review and assess the update studies regarding medical treatment for premature ejaculation (PE. It is the most common sexual problem affecting men. It can affect men at all ages and has a serious impact on the quality of life for men and their partners. A wide variety of therapeutic modalities have been tried for treatment of premature ejaculation. Psychological therapies may be helpful for patients with complaint PE. Several topical therapies have been used including lidocaine cream, lidocaine-prilocaine cream. There has been recent interest in the selective serotonin reuptake inhibitors (SSRI for the treatment of PE, due to the fact that one of their common side effects is delayed ejaculation. Currently used SSRIs have several non-sexual side effects and long half lives, therefore there has been interest in developing a short acting, and efficacious SSRI that can be used on-demand for PE. Dapoxetine has been recently evaluated for the treatment of PE by several groups, and results so far appear promising.
Full Text Available The HER2/neu ( ERBB2 oncogene is amplified and/or overexpressed in approximately 20% of breast cancers, and is a strong prognostic factor for relapse and poor overall survival, particularly in node-positive patients. It is also an important predictor for response to trastuzumab, which has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. Treatment with the anti-HER2 humanized monoclonal antibody – trastuzumab significantly improves progression-free and overall survival among patients with HER2-positive breast cancer. However, in most patients with HER2-positive metastatic breast cancer, the disease progresses occurred, what cause the need for new targeted therapies for advanced disease. In clinical trials, there are tested new drugs to improve the results of treatment for this group of patients. This paper presents new drugs introduced into clinical practice for treatment of advanced breast cancer, whose molecular target are receptors of the HER2 family. In addition, new therapeutic strategies and drugs that are currently in clinical researches are discussed.
Bellamoli, Elisa; Manganotti, Paolo; Schwartz, Robert P; Rimondo, Claudia; Gomma, Maurizio; Serpelloni, Giovanni
Drug addiction can be a devastating and chronic relapsing disorder with social, psychological, and physical consequences, and more effective treatment options are needed. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique that has been assessed in a growing number of studies for its therapeutic potential in treating addiction. This review paper offers an overview on the current state of clinical research in treating drug addiction with rTMS. Because of the limited research in this area, all studies (including case reports) that evaluated the therapeutic use of rTMS in nicotine, alcohol, or illicit drug addiction were included in this review. Papers published prior to December 2012 were found through an NCBI PubMed search. A total of eleven studies were identified that met review criteria. There is nascent evidence that rTMS could be effective in reducing cocaine craving and nicotine and alcohol craving and consumption and might represent a potential therapeutic tool for treating addiction. Further studies are needed to identify the optimal parameters of stimulation for the most effective treatment of drug addiction, to improve our comprehension of the treatment neurophysiological effects, and to conduct rigorous, controlled efficacy studies with adequate power.
Cesaro, P; Defebvre, L
In this article, we discuss the management of motor symptoms during the early phases of Parkinson's disease, excluding that of any other clinical manifestation. We relied primarily upon recently published data and do not describe older publications relating to anticholinergic drugs or amantadine. The initial pharmacological treatment of idiopathic Parkinson's disease (IPD) is symptomatic and remains based upon dopaminergic drugs. However, the development of new drugs has broadened the range of strategic options and improved overall patient management. Announcing the diagnosis is a critical moment, as pointed out by patients' associations. Patients should be advised to maintain personal, professional, social and physical activities as long as possible. The potential benefit of early pharmacological treatment should be explained, focusing on the possible disease-modifying effect of drugs such as rasagiline. According to current guidelines, L-Dopa is preferred in patients above 65years of age, while those below 65 should be treated with dopamine agonists. Like monoamine oxidase inhibitors B (MAOI-B), synthetic dopamine agonists exhibit several advantages: easy-to-use treatment with a once-daily administration, delayed L-Dopa initiation, significant efficacy on motor symptoms (although lower than that of L-Dopa). MOAI can be prescribed in association with L-Dopa or dopamine agonists. Rasagiline also delays L-Dopa initiation, and consequently motor complications. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Full Text Available The clinical effectiveness of headache treatment by transcranial direct current stimulation with various locations of stimulating electrodes on the scalp was analyzed retrospectively. The results of the treatment were analyzed in 90 patients aged from 19 to 54 years (48 patients had migraine without aura, 32 – frequent episodic tension-type headaches, 10 – chronic tension-type headaches and in 44 adolescents aged 11 – 16 years with chronic posttraumatic headaches after a mild head injury. Clinical effectiveness of tDCS with 70 – 150 µA current for 30 – 45 minutes via 6.25 cm2 stimulating electrodes is comparable to that of modern pharmacological drugs, with no negative side effects. The obtained result has been maintained on average from 5 to 9 months. It has been demonstrated that effectiveness depends on localization of stimulating electrodes used for different types of headaches.
Ioset, Jean-Robert; Chang, Shing
The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven organization committed to the development of new treatments for neglected diseases. Created in 2003, DNDi has delivered four improved treatments for malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is to build a solid R&D portfolio for neglected diseases and to deliver preclinical candidates in a timely manner using an original model based on partnership. To address this challenge DNDi has remodeled its discovery activities from a project-based academic-bound network to a fully integrated process-oriented platform in close collaboration with pharmaceutical companies. This discovery platform relies on dedicated screening capacity and lead-optimization consortia supported by a pragmatic, structured and pharmaceutical-focused compound sourcing strategy.
Full Text Available Elena Monti1, Monica Mottes1, Paolo Fraschini2, PierCarlo Brunelli3, Antonella Forlino4, Giacomo Venturi1, Francesco Doro1, Silvia Perlini1, Paolo Cavarzere1, Franco Antoniazzi11Department of Life Sciences and Reproduction, Pediatric Clinic University of Verona, Verona, Italy; 2Istituto Di Ricovero e Cura a Carattere Scientifico, ‘E. Medea’, Associazione La Nostra Famiglia, Bosisio Parini (LC, Italy; 3Divisione di Ortopedia Pediatrica, Spedali Civili, Brescia, Italy; 4Department of Biochemistry “A. Castellani”, University of Pavia, ItalyAbstract: Osteogenesis imperfecta (OI is the most common bone genetic disorder and it is characterized by bone brittleness and various degrees of growth disorder. Clinical severity varies widely; nowadays eight types are distinguished and two new forms have been recently described although not yet classified. The approach to such a variable and heterogeneous disease should be global and therefore multidisciplinary. For simplicity, the objectives of treatment can be reduced to three typical situations: the lethal perinatal form (type II, in which the problem is survival at birth; the severe and moderate forms (types III–IX, in which the objective is ‘autonomy’; and the mild form (type I, in which the aim is to reach ‘normal life’. Three types of treatment are available: non-surgical management (physical therapy, rehabilitation, bracing and splinting, surgical management (intramedullary rod positioning, spinal and basilar impression surgery and medical-pharmacological management (drugs to increase the strength of bone and decrease the number of fractures as bisphosphonates or growth hormone, depending on the type of OI. Suggestions and guidelines for a therapeutic approach are indicated and updated with the most recent findings in OI diagnosis and treatment.Keywords: osteogenesis imperfecta, bone genetic disorder, bone brittleness, “brittle bone disease”, connective tissue malfunction, short
R. A. Gafanov
Full Text Available Prostate cancer (PC is one of the most common causes of death from malignant neoplasms in men in many countries around the world. Transmission of the signal in the androgenic axis of regulation is crucial for the development and progression of PC. Despite the constant dependence on androgen receptor signals in castration resistance, the use of new anti-androgenic drugs invariably leads to the stability of the ongoing treatment. The interaction of androgen receptor and alternative (phosphoinositide-3-kinases, PI3K pathways in the regulation of cells can be one of the mechanisms of resistance to treatment. In this article, we describe current treatments for metastatic castration-resistant PC and the possible role of the PI3K pathway in the pathogenesis and progression of PC.
Liu, Lin; Yao, WenDong; Rao, YueFeng; Lu, XiaoYang; Gao, JianQing
Oral administration is a desirable alternative of parenteral administration due to the convenience and increased compliance to patients, especially for chronic diseases that require frequent administration. The oral drug delivery is a dynamic research field despite the numerous challenges limiting their effective delivery, such as enzyme degradation, hydrolysis and low permeability of intestinal epithelium in the gastrointestinal (GI) tract. pH-Responsive carriers offer excellent potential as oral therapeutic systems due to enhancing the stability of drug delivery in stomach and achieving controlled release in intestines. This review provides a wide perspective on current status of pH-responsive oral drug delivery systems prepared mainly with organic polymers or inorganic materials, including the strategies used to overcome GI barriers, the challenges in their development and future prospects, with focus on technology trends to improve the bioavailability of orally delivered drugs, the mechanisms of drug release from pH-responsive oral formulations, and their application for drug delivery, such as protein and peptide therapeutics, vaccination, inflammatory bowel disease (IBD) and bacterial infections.
Ibaraki, Ai; Goto, Wataru; Iura, Rie; Tominaga, Mitsuhiro; Tsuchihashi, Takuya
The guidelines for the management of hypertension recommend the inclusion of diuretics, especially when three or more antihypertensive drugs are used. The present study investigated the current prescription status of antihypertensive drugs with a particular focus on the use of diuretics in a local district in Japan. Prescriptions, including antihypertensive drugs, were collected from a dispensing pharmacy of the Yahata Pharmacist Association, located in Kitakyushu City, in October 2014. Of the 10 585 prescriptions, calcium channel blockers (CCBs) were prescribed in 73.5%, followed by angiotensin II receptor blockers (ARB, 62.7%), diuretics (16.5%) and β-blockers (13.6%). The average number of drugs used was 1.80. The rates of prescription of diuretics for patients with one, two, three and four drugs were 0.6%, 13.1%, 55.2% and 82.6%, respectively. Diuretics were more frequently prescribed in elderly patients, and the prescription rate of doctors in hospitals was significantly higher than that of general practitioners (19.1% vs. 15.7%, Pdiuretics were prescribed combination tablets of hydrochlorothiazide with ARB, whereas trichlormethiazide (34.9%) and indapamide (19.8%) were used in other patients. Based on these findings, the use of diuretics remains limited, even among patients taking multiple antihypertensive drugs.
Nakano, Masataka; Nakajima, Miki
Understanding the factors causing inter- and intra-individual differences in drug metabolism potencies is required for the practice of personalized or precision medicine, as well as for the promotion of efficient drug development. The expression of drug-metabolizing enzymes is controlled by transcriptional regulation by nuclear receptors and transcriptional factors, epigenetic regulation, such as DNA methylation and histone acetylation, and post-translational modification. In addition to such regulation mechanisms, recent studies revealed that microRNAs (miRNAs), endogenous ~22-nucleotide non-coding RNAs that regulate gene expression through the translational repression and degradation of mRNAs, significantly contribute to post-transcriptional regulation of drug-metabolizing enzymes. Areas covered: This review summarizes the current knowledge regarding miRNAs-dependent regulation of drug-metabolizing enzymes and transcriptional factors and its physiological and clinical significance. We also describe recent advances in miRNA-dependent regulation research, showing that the presence of pseudogenes, single-nucleotide polymorphisms, and RNA editing affects miRNA targeting. Expert opinion: It is unwavering fact that miRNAs are critical factors causing inter- and intra-individual differences in the expression of drug-metabolizing enzymes. Consideration of miRNA-dependent regulation would be a helpful tool for optimizing personalized and precision medicine.
Flaherty, E W; Olsen, K; Bencivengo, M
Recent sharp decline in treatment admissions by opiate abusers stimulated the conduct of a study designed to provide timely data to treatment system administrators for the next cycle of program and budgetary planning. The process of designing the study involved definition of required study characteristics, review of four categories of drug abuse research, and generation of seven locally relevant hypotheses. Interviews were conducted with 335 heroin adicts: 196 new admissions to treatment and 139 "street" addicts not currently in treatment. Major findings were a marked reduction in the quality, availability, and price of heroin; very negative perceptions of methadone maintenance, especially by female respondents; decline in heroin popularity and increase in reported use of alcohol, amphetamines, and barbiturates; and differing perceptions of treatment by sex of respondent. Response patterns suggest that users who are not entering treatment are less "strung-out than those entering treatment because of decline in availability and quality of heroin and consequent increased mixing of drugs. The emphasis in the report is on the conduct of a study which can be timely, feasible, and useful to local planners. The study weaknesses and recommended remedies are discussed, as well as the characteristics which made the findings immediately useful to administrators and planners.
Nelson, Antoinette G; Zhang, Xiaoping; Ganapathi, Usha; Szekely, Zoltan; Flexner, Charles W; Owen, Andrew; Sinko, Patrick J
The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today. Moving forward there are at least three high priority goals for anti-HIV drug delivery (DD) research: (1) to prevent new HIV infections from occurring, (2) to facilitate a functional cure, i.e., when HIV is present but the body controls it without drugs and (3) to eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a significant step forward in preventing the establishment of chronic HIV infection. However, the ultimate success of PrEP will depend on achieving sustained antiretroviral (ARV) tissue concentrations and will require strict patient adherence to the regimen. While first generation long acting/extended release (LA/ER) DD Systems (DDS) currently in development show considerable promise, significant DD treatment and prevention challenges persist. First, there is a critical need to improve cell specificity through targeting in order to selectively achieve efficacious drug concentrations in HIV reservoir sites to control/eradicate HIV as well as mitigate systemic side effects. In addition, approaches for reducing cellular efflux and metabolism of ARV drugs to prolong effective concentrations in target cells need to be developed. Finally, given the current understanding of HIV pathogenesis, next generation anti-HIV DDS need to address selective DD to the gut mucosa and lymph nodes. The current review focuses on the DDS technologies, critical challenges, opportunities, strategies, and approaches by which novel
Leonard, Elizabeth Weeks
On May 2, 2006, a divided panel of the U.S. Court of Appeals for the District of Columbia, in a startling opinion, Abigail Alliance for Better Access to Developmental Drugs v. Eschenbach, held that terminally ill patients who have exhausted all other available options have a constitutional right to experimental treatment that FDA has not yet approved. Although ultimately overturned by the full court, Abigail Alliance generated considerable interest from various constituencies. Meanwhile, FDA proposed similar regulatory amendments, as have lawmakers on both sides of the aisle in Congress. But proponents of expanded access fail to consider public health and consumer safety concerns. In particular, allowing patients to try unproven treatments, outside of controlled clinical trials risks both the study's outcome and the health of patients who might benefit from the deliberate, careful process of new drug approval as it currently operates under FDA's auspices.
Drekonja, Dimitri M
Clostridium difficile infection (CDI) has increased in incidence and severity, and is now among the most common nosocomial infections. Several agents are available for the initial treatment of CDI, some of which are rarely used, and none of which is clearly superior for initial clinical cure. Fidaxomicin appears to offer a benefit in terms of preventing recurrent disease, although the cost-benefit ratio is debated. Recurrent CDI is a major challenge, occurring after 15-30% of initial episodes. The treatment of recurrent CDI is difficult, with sparse evidence available to support any particular agent. Fecal microbiota therapy, also known as 'stool transplantation', appears to be highly effective, although availability is currently limited, and the regulatory environment is in flux. Synthetic stool products and an orally available fecal microbiota therapy product are both under investigation, which may address the problem of availability. As with most infectious diseases, an effective vaccine would be a welcome addition to our armamentarium, but none is currently available.
Moody, Lara; Satterwhite, Emily; Bickel, Warren K
The burden of substance use and especially the unmatched rates of overdoses in rural Central Appalachia highlight the need for innovative approaches to curb the initiation to drug misuse and to address current substance use disorders. Effective substance use interventions involve a thorough understanding of the region. In Central Appalachia, many of the barriers to treatment are shared with other rural and impoverished areas, including a lack of access to health care and lack of health care providers with specialized training. Parts of Appalachia also present their own considerations, including the challenges of fostering trust and encouraging treatment-seeking in communities with dense, long-term, place-based social and family networks. Current policies and interventions for substance use have been largely inadequate in the region, as evidenced by continued increases in substance use and substance-related deaths, especially related to nonmedical prescription drug use and increasing heroin use. The authors discuss ways in which rural life, poverty, identity, and values in Appalachia have influenced substance use and treatment and propose strategies and interventions to improve outcomes.
Full Text Available Montserrat López-Rubio,1 Jose Antonio Garcia-Marco2 1Department of Hematology, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, 2Department of Hematology, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, Spain Abstract: Hairy cell leukemia (HCL is a lymphoproliferative B-cell disorder characterized by pancytopenia, splenomegaly, and characteristic cytoplasmic hairy projections. Precise diagnosis is essential in order to differentiate classic forms from HCL variants, such as the HCL-variant and VH4-34 molecular variant, which are more resistant to available treatments. The current standard of care is treatment with purine analogs (PAs, such as cladribine or pentostatin, which provide a high rate of long-lasting clinical remissions. Nevertheless, ~30%–40% of the patients relapse, and moreover, some of these are difficult-to-treat refractory cases. The use of the monoclonal antibody rituximab in combination with PA appears to produce even higher responses, and it is often employed to minimize or eliminate residual disease. Currently, research in the field of HCL is focused on identifying novel therapeutic targets and potential agents that are safe and can universally cure the disease. The discovery of the BRAF mutation and progress in understanding the biology of the disease has enabled the scientific community to explore new therapeutic targets. Ongoing clinical trials are assessing various treatment strategies such as the combination of PA and anti-CD20 monoclonal antibodies, recombinant immunotoxins targeting CD22, BRAF inhibitors, and B-cell receptor signal inhibitors. Keywords: hairy cell leukemia, purine analogs, rituximab, immunotoxins, vemurafenib, ibrutinib
Suehiro, Eiichi; Yoshino, Hiroko; Koizumi, Hiroyasu; Yoneda, Hiroshi; Suzuki, Michiyasu
Despite neurotrauma treatment practices comprising a significant amount of neurosurgical work for secondary medical service centers, little attention has been placed on neurotrauma cases and evaluation of current neurotrauma treatment practices is limited. Therefore we investigated current neurotrauma practices in our hospital located in a Japanese suburban city. We analyzed 439 patients with traumatic brain injury (TBI) admitted to our hospital between April 2004 and October 2010. Patients were divided into three groups based on the Glasgow Coma Scale (GCS) score on admission: mild TBI (GCS 14-15) in 252 patients (57.4%), moderate TBI (GCS 9-13) in 116 patients (26.4%), and severe TBI (GCS 3-8) in 71 patients (16.2%). Age, gender, alcohol consumption, cause of injury, cranial CT findings, neurosurgical procedure, length of hospital stay, and clinical outcome were analyzed. The average age of the patients was 59.2 years old. Male patients comprised 65%. Alcohol consumption was reported in 81 cases (18.5%), most of them with moderate TBI. Fall (208 cases, 47.4%) was the most frequent cause of injury, followed by traffic accident (115 cases, 26.2%) and high fall (73 cases, 16.6%). Acute subdural hematoma (174 cases, 39.6%) was most frequently seen in cranial CT findings on admission, which significantly increased with severity. A neurosurgical procedure was performed for 70 cases (15.9%), of which 15 (6.0%) were mild TBI and 18 (15.5%) were moderate TBI. The average hospital stay was 20.8 days, which significantly increased with severity. The overall rate of favorable outcome was 82.7%, and mortality was 8.2%; outcome deteriorated with severity. Some mild and moderate TBI cases had deteriorated and required surgery or resulted in death. These findings suggest that cautious treatment is necessary even in mild to moderate TBI cases which are often encountered in secondary medical service centers. (author)
Shams Najafabadi, Hoda; Daftarian, Narsis; Ahmadieh, Hamid; Soheili, Zahra-Soheila
Age-related macular degeneration as the major cause of blindness in the elderly population has remained at the epicenter of clinical research in ophthalmology. This retinal disorder is characterized by the photoreceptor and retinal pigment epithelial cells loss, occurring within the macula. The disease represents a spectrum of clinical manifestations. It is a multifactorial disease resulting from a combination of genetic predispositions and environmental risk factors. AMD is classified into two different types, dry and wet. Wet AMD is in close relation with angiogenesis and inflammatory processes.A variety of anti-angiogenesis and anti-inflammatory drugs have been proposed for the treatment of the disease. The purpose of this paper is to briefly review the pharmacological therapies of the wet form of AMD and focus on new drugs that are currently in different stages of research and development.
World Health Organization grade II gliomas (GIIGs) include diffuse astrocytoma, oligodendroglioma, and oligoastrocytoma. GIIG is a malignant brain tumor for which the treatment outcome can still be improved. Review of previous clinical trials found the following: GIIG increased in size by 3-5 mm per year when observed or treated with surgery alone; after pathological diagnosis, the survival rate was increased by early aggressive tumor removal at an earlier stage compared to observation alone; although the prognosis after total tumor removal was significantly better than that after partial tumor removal, half of the patients relapsed within 5 years; comparing postoperative early radiotherapy (RT) and non-early RT after relapse, early RT prolonged progression-free survival (PFS) but did not affect overall survival (OS); local RT of 45 to 64.8 Gy did not impact PFS or OS; in patients with residual tumors, RT combined with chemotherapy (procarbazine plus lomustine plus vincristine) prolonged PFS compared with RT alone but did not affect OS; and poor prognostic factors included astrocytoma, non-total tumor removal, age ≥40 years, largest tumor diameter ≥4-6 cm, tumor crossing the midline, and neurological deficit. To improve treatment outcomes, surgery with functional brain mapping or intraoperative magnetic resonance imaging or chemoradiotherapy with temozolomide is important. In this review, current knowledge regarding GIIG is described and treatment strategies are explored. (author)
Takahashi, Tsunehiro; Saikawa, Yoshiro; Kitagawa, Yuko
Gastric cancer is the second leading cause of death from malignant disease worldwide and most frequently discovered in advanced stages. Because curative surgery is regarded as the only option for cure, early detection of resectable gastric cancer is extremely important for good patient outcomes. Therefore, noninvasive diagnostic modalities such as evolutionary endoscopy and positron emission tomography are utilized as screening tools for gastric cancer. To date, early gastric cancer is being treated using minimally invasive methods such as endoscopic treatment and laparoscopic surgery, while in advanced cancer it is necessary to consider multimodality treatment including chemotherapy, radiotherapy, and surgery. Because of the results of large clinical trials, surgery with extended lymphadenectomy could not be recommended as a standard therapy for advanced gastric cancer. Recent clinical trials had shown survival benefits of adjuvant chemotherapy after curative resection compared with surgery alone. In addition, recent advances of molecular targeted agents would play an important role as one of the modalities for advanced gastric cancer. In this review, we summarize the current status of diagnostic technology and treatment for gastric cancer
Jordan, Natasha; D’Cruz, David
Systemic lupus erythematosus (SLE) is a complex autoimmune disease with variable clinical manifestations. While the clearest guidelines for the treatment of SLE exist in the context of lupus nephritis, patients with other lupus manifestations such as neuropsychiatric, hematologic, musculoskeletal, and severe cutaneous lupus frequently require immunosuppression and/or biologic therapy. Conventional immunosuppressive agents such as mycophenolate mofetil, azathioprine, and cyclophosphamide are widely used in the management of SLE with current more rationalized treatment regimens optimizing the use of these agents while minimizing potential toxicity. The advent of biologic therapies has advanced the treatment of SLE particularly in patients with refractory disease. The CD20 monoclonal antibody rituximab and the anti-BLyS agent belimumab are now widely in use in clinical practice. Several other biologic agents are in ongoing clinical trials. While immunosuppressive and biologic agents are the foundation of inflammatory disease control in SLE, the importance of managing comorbidities such as cardiovascular risk factors, bone health, and minimizing susceptibility to infection should not be neglected. PMID:27529058
Balmaceda, Casilda M
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a standard treatment for osteoarthritis (OA), but the use of oral NSAIDs has been linked to an elevated risk for cardiovascular and gastrointestinal adverse events and renal toxicity. Topical NSAIDs are thought to afford efficacy that is comparable to oral formulations while reducing widespread systemic drug exposure, which may provide a benefit in terms of safety and tolerability. As a result, European treatment guidelines have, for many years, recommended the use of topical NSAIDs as a safe and effective treatment option for OA. Following the recent approval of several topical NSAID formulations by the US Food and Drug Administration, US treatment guidelines are increasingly recommending the use of topical NSAIDs as an alternative therapy and, in some cases, as a first-line option for OA. This commentary summarizes OA treatment guidelines that are currently available and discusses their potential evolution with regard to the increased inclusion of topical NSAIDs.
To document the evolution over 40 years (from 1973 to 2013) of Coolmine Therapeutic Community (Ireland's first voluntary drug treatment service) against a background of broader drug policy developments in the Republic of Ireland and elsewhere during this period. Data were gathered by means of archival research within Coolmine, complemented by semi-structured interviews with former clients, current and former Coolmine management and staff, and representatives of outsider stakeholder interests. Coolmines's history has three phases: (1) an early and uncontentious phase, in which external authorities provided financial support for Coolmine without questioning its work practices or outcomes; (2) a middle, controversial phase, in which Coolmine struggled for survival in an external policy environment now dominated by harm reduction strategies; and (3) a final phase in which, through the use of conventional corporate governance, Coolmine management sought to repair its damaged reputation by introducing evidence-based clinical practices. Coolmine Therapeutic Community was established when drug treatment services in Ireland were in their infancy, and its changing fortunes over subsequent decades reflected changing perceptions of what constitutes appropriate addiction treatment-and in particular the role to be played by former addicts within addiction treatment systems-as well as changing perceptions of funding relationships between statutory authorities and voluntary providers of health and social services. © 2015 Society for the Study of Addiction.
Sloop, Kyle W; Emmerson, Paul J; Statnick, Michael A; Willard, Francis S
One approach of modern drug discovery is to identify agents that enhance or diminish signal transduction cascades in various cell types and tissues by modulating the activity of GPCRs. This strategy has resulted in the development of new medicines to treat many conditions, including cardiovascular disease, psychiatric disorders, HIV/AIDS, certain forms of cancer and Type 2 diabetes mellitus (T2DM). These successes justify further pursuit of GPCRs as disease targets and provide key learning that should help guide identifying future therapeutic agents. This report reviews the current landscape of GPCR drug discovery with emphasis on efforts aimed at developing new molecules for treating T2DM and obesity. We analyse historical efforts to generate GPCR-based drugs to treat metabolic disease in terms of causal factors leading to success and failure in this endeavour. © 2018 The British Pharmacological Society.
Over time, there have been considerable changes in the variety, availability, production, distribution, and use and user(s) of psychoactive substances, the meaning of substance use and its impact on users and their social or physical environment(s). This article reviews the mechanisms of introduction of psychoactive substances such as alcohol, tobacco, coffee, tea and cannabis to populations and communities that did not have them before. It considers the historical tension between early adopters who greet new substances with various levels of enthusiasm in their eagerness to enjoy what they believe to be the benefits of using these substances, and those focused on what they believe to be the negative aspects of use, who decry these new substances with horror. With more nonusers than users in the population, social policies tend to be directed at preventing, restricting, or punishing selected use, users and .drugs., using controls and interventions such regulation, incarceration, death sentence, treatment, prevention, legalization, taxation, among others. Whatever their intent or wished-for impact, all had consequences that produced additional, unplanned for, and (often) negative effects. This paper will consider some of these sequences as they occurred historically with other substances in light of the current shift to legalization and normalization of cannabis, noting the mechanisms of use, controls, and consequences of some types of formal interventions and give some attention to how and what we can learn from our experiences in order to plan ahead and become better prepared to successfully deal with the 'unexpecteds' of that well-known 'hell' paved with good intentions.
Full Text Available Pancreatic ductal adenocarcinoma (PDAC represents permanent and ever rising issue worldwide. Five-year survival does not exceed 3 to 6%, i.e. the worst result among solid tumours. The article evaluates the current state of PDAC diagnostics and treatment specifying also development and trends. Percentage of non-resectable tumours due to locally advanced or metastatic condition varies 60–80%, mostly over 80%. Survival with non-resectable PDAC is 4 to 8 months (median 3.5. In contrast R0 resection shows the survival 18–27 months. Laboratory and imaging screening methods are not indicated on large scale. Risk factors are smoking, alcohol abuse, chronic pancreatitis, diabetes mellitus. Genetic background in most PDAC has not been detected yet. Some genes connected with high risk of PDAC (e.g. BRCA2, PALB2 have been identified as significant and highly penetrative, but link between PDAC and these genes can be seen only in 10–20%. This article surveys perspective oncogenes, tumour suppressor genes, microRNA. Albeit CT is still favoured over other imaging methods, involvement of NMR rises. Surgery prefers the “vessel first” approach, which proves to be justified especially in R0 resection. According to EBM immunotherapy same as radiotherapy are not significant in PDAC treatment. Chemotherapy shows limited importance in conversion treatment of locally advanced or borderline tumours or in case of metastatic spread. Unified procedures cannot be defined due to inhomogenous arrays. Surgical resection is the only chance for curative treatment of PDAC and depends mainly on timely indication for surgery and quality of multidisciplinary team in a high-volume centre.
Full Text Available The prevalence of hepatitis C virus (HCV infection is disproportionately high among prisoners, especially among those who are drug-dependent. However, current screening and treatment recommendations are inconsistent for this population, and appropriate care is not reliably provided. To address these problems, the present study aimed to identify unique characteristics and clinical manifestations of incarcerated patients with HCV infection. We included incarcerated patients who received treatment with pegylated-interferon combined with ribavirin at Mackay Memorial Hospital in Taitung and were serving sentences at either the Taiyuan Skill Training Institute or the Yanwan Training Institute. HCV genotypes 1 (41.4%, 3 (25.9%, and 6 (24.1% were the most prevalent in the incarcerated patients. During the study period, we analyzed treatment response among 58 incarcerated patients and compared obtained results with treatment response among 52 patients who were living in the community. Higher sustained virological response rate was observed among patients with incarceration and HCV genotype other than 1. The odds ratios (corresponding 95% confidence intervals for incarceration and genotype 1 were 2.75 (1.06-7.11 and 0.37 (0.14-0.99, respectively. Better treatment compliance among incarcerated patients might partially explain these results. The results of this study suggest that treatment of prisoners with HCV infection is feasible and effective. More appropriate and timely methods are needed to prevent HCV transmission among injection drug users inside prisons.
Chouaid, Christos; Borget, Isabelle; Braun, Eric; Bazil, Marie-Laure; Schaetz, Dominique; Rémuzat, Cécile; Toumi, Mondher
France is one of the European countries that spend the most on oncology drugs. To keep pharmaceutical expenditure under control, Health Authorities highly scrutinize market access of costly medicines. To assess current and future trends in French health technology assessment (HTA) of antineoplastic drugs indicated in the treatment of solid tumours. A review of the SMR and ASMR drivers of the Transparency Committee (CT) opinions issued for antineoplastic drugs indicated in the treatment of solid tumours and approved between 2009 and 2014 was performed to assess current trends in French health technology assessment (HTA), complemented by an expert board consultation to capture the critical issues on the future of antineoplastic drugs HTA. Thirty-one drugs indicated for the treatment of solid tumours were identified (77 % targeted therapies). Initial CT assessments were available for 26 drugs. Four key items in the CT assessment were identified: 1) Clinical trial methodology; 2) Acceptance of progression-free survival (PFS) as a valuable endpoint; 3) Transferability of clinical trials in clinical practice; 4) Unpredictability of CT decisions. Experts raised the important development of personalised medicines in oncology and key challenges for oncology products to generate information expected from HTA perspective. The French system remains committed to its values and philosophy (access of all innovations for everybody) which are threatened by the increasing launch of innovative therapies and budget constraint. Both HTA decision framework evolution and revision of the current pricing process should be considered in France to cope with these new challenges.
Cruz, Rossilene Conceição da Silva; Bührer-Sékula, Samira; Penna, Maria Lúcia F; Penna, Gerson Oliveira; Talhari, Sinésio
In this review, the most relevant and current epidemiological data, the main clinical, laboratory and therapeutical aspects of leprosy are presented. Detailed discussion of the main drugs used for leprosy treatment, their most relevant adverse effects, evolution of the therapeutic regimen, from dapsone as a monotherapy to the proposed polychemotherapy by World Health Organization (WHO) can be found in this CME. We specifically highlight the drug acceptability, reduction in treatment duration and the most recent proposal of a single therapeutic regimen, with a fixed six months duration, for all clinical presentations, regardless of their classification.
Belenko, Steven; Foltz, Carol; Lang, Michelle A.; Sung, Hung-En
Recent interest in increasing access to substance abuse treatment for drug-involved offenders has been spurred by concerns over expanding prison and jail populations, high recidivism rates for drug-involved offenders, and the close link between illegal drug use and criminal activity. Chronic untreated drug and alcohol abuse is likely to result in…
Sorensen, Andrew A.; Leske, M. Cristina
This paper, presented at the American Public Health Association meeting; Chicago, November 1975, discusses a staff training program at a drug addiction treatment facility established for Spanish-speaking (and other) drug addicts. Staff improved counseling skills and knowledge of drug addiction, but changed little in attitudes toward drug use and…
Issa, Maria Claudia Almeida; Pires, Marianna; Silveira, Priscilla; Xavier de Brito, Esther; Sasajima, Cristiane
Transepidermal drug delivery (TED) is a new potential method in dermatology. Permeability alterations induced by ablative fractional resurfacing have been described with the aim to increasing the delivery of different substances into the skin. To evaluate clinical response and side effects of TED in areata alopecia (AA) treatment using ablative fractional methods associated with acoustic pressure ultrasound (US) to deliver triamcinolone solution into the skin. Five cases of AA underwent treatment which comprised of 3 steps: 1) Ablative fractioned RF or CO2 laser 2) topical application of triamcinolone 3) acoustic pressure wave US. The number of sessions varied according to the clinical response, ranging from one to six sessions. All patients had complete recovery of the area treated. Two of them treated with ablative fractional RF + triamcinolone + US had complete response after three and six sessions. The other two treated with ablative fractional CO2 + triamcinolone + US had complete response after one session. Fractioned ablative resurfacing associated with acoustic pressure wave US is a new option to areata alopecia treatment with good clinical result and low incidence of side effects.
P LA van Daele
Full Text Available P LA van Daele, J H Kappen, P M van Hagen, J AM van LaarDepartment of Internal Medicine, Department of Immunology, Erasmus MC, ‘s Gravendijkwal 230, 3015 Ce Rotterdam, The NetherlandsAbstract: Behçet’s disease is an autoinflammatory vasculitis of unknown origin characterized by recurrent oral and genital ulcers, uveitis, arthritis and skin lesions. Additionally, involvement of the gastrointestinal tract, central nervous system and large vessels may occur. The disease is prevalent in countries along the ancient Silk Road from Eastern Asia to the Mediterranean Basin. Many treatment modalities are currently available. The choice of treatment depends on organ involvement and severity of disease. Topical treatment with corticosteroids is often sufficient for mucocutaneous involvement, however for more severe disease with vasculitis or neurological involvement a more aggressive approach is warranted. Newer drugs (biologicals influencing cytokines and thereby T-cell function are promising with an acceptable side effect profile. Unfortunately, reimbursement of the costs of biologicals for rare disease is still a problem in various countries. In this report we discuss the current treatment modalities for Behçet’s disease.Keywords: Behçet’s disease, biologicals, treatment
Full Text Available Recent advances in the treatment of pulmonary arterial hypertension (PAH have led to improved patient outcomes. Multiple PAH therapies are now available and optimising the use of these drugs in clinical practice is vital. In this review, we discuss the management of PAH patients in the context of current treatment guidelines and supporting clinical evidence. In clinical practice, considerable emphasis is placed on the importance of making treatment decisions guided by each patient's risk status, which should be assessed using multiple prognostic parameters. As PAH is a progressive disease, regular assessments are essential to ensure that any change in risk is detected in a timely manner and treatment is adjusted accordingly. With the availability of therapies that target three different pathogenic pathways, combination therapy is now the standard of care. For most patients, this involves dual combination therapy with agents targeting the endothelin and nitric oxide pathways. Therapies targeting the prostacyclin pathway should be added for patients receiving dual combination therapy who do not achieve a low-risk status. There is also a need for a holistic approach to treatment beyond pharmacological therapies. Implementation of all these approaches will ensure that PAH patients receive maximal benefit from currently available therapies.
Brandão, Mariana; Pondé, Noam F; Poggio, Francesca; Kotecki, Nuria; Salis, Mauren; Lambertini, Matteo; de Azambuja, Evandro
HER2-positive disease is an aggressive subtype of breast cancer that has been revolutionized by anti-HER2 directed therapies. Multiple drugs have been developed and are currently in clinical use, including trastuzumab, lapatinib, pertuzumab, T-DM1, and neratinib, alone or combined in 'dual HER2-blockade' regimens. Areas covered: A comprehensive literature review was performed regarding the current state and the future of combination regimens containing anti-HER2 agents, focusing on their efficacy, toxicity, and cost-effectiveness. Expert commentary: The combination of trastuzumab/pertuzumab is approved in all disease settings, while trastuzumab/neratinib is approved in the adjuvant setting and trastuzumab/lapatinib in metastatic disease. Meanwhile, as breast cancer biology and resistance mechanisms become clearer, combinations with drugs like PI3K/Akt/mTOR inhibitors, CDK4/6 inhibitors, anti-PD(L)1 antibodies, endocrine therapy, and new anti-HER2 agents (panHER and HER2 tyrosine kinase inhibitors, bispecific antibodies, anti-HER3 antibodies, and antibody-drug conjugates) are being extensively tested in clinical trials. More specific strategies for the 'triple-positive' (estrogen receptor-positive/HER2-positive) disease are also being explored. However, there is an urgent need for the development of predictive biomarkers for a better tailoring of anti-HER2 directed therapy. This is the only way to further improve clinical outcomes and quality of life and to decrease costs and toxicities of unnecessary treatments.
Penna, F; Pin, F; Ballarò, R; Baccino, F M; Costelli, P
Cachexia is a syndrome characterized by body weight loss, muscle wasting and metabolic abnormalities, that frequently complicates the management of people affected by chronic diseases. No effective therapy is actually available, although several drugs are under clinical evaluation. Altered energy metabolism markedly contributes to the pathogenesis of cachexia; it can be improved by exercise, which is able to both induce anabolism and inhibit catabolism. This review focuses on exercise mimetics and their potential inclusion in combined protocols to treat cachexia. The authors pay with particular reference to the cancer-associated cachexia. Even though exercise improves muscle phenotype, most patients retain sedentary habits which are quite difficult to disrupt. Moreover, they frequently present with chronic fatigue and comorbidities that reduce exercise tolerance. For these reasons, drugs mimicking exercise could be beneficial to those who are unable to comply with the practice of physical activity. Since some exercise mimetics may exert serious side effects, further investigations should focus on treatments which maintain their effectiveness on muscle phenotype while remaining tolerable at the same time.
Silva, M R; Pereira, J C; Costa, R R; Dias, J A; Guimarães, M D C; Leite, I C G
This study aimed to evaluate the risk factors for tuberculosis (TB) treatment default in a priority city for disease control in Brazil. A cohort of TB cases diagnosed from 2008 to 2009 was followed up from patients' entry into three outpatient sites, in Juiz de Fora, Minas Gerais (Brazil), until the recording of the outcomes. Drug addiction, alcoholism and treatment site appeared to be independently associated with default. Current users of crack as the hardest drug (odds ratio (OR) 12·25, 95% confidence interval (CI) 3·04-49·26) were more likely to default than other hard drug users (OR 5·67, 95% CI 1·34-24·03), former users (OR 4·12, 95% CI 1·11-15·20) and those not known to use drugs (reference group). Consumers at high risk of alcoholism (OR 2·94, 95% CI 1·08-7·99) and those treated in an outpatient hospital unit (OR 8·22, 95% CI 2·79-24·21%) also were more likely to default. Our results establish that substance abuse was independently associated with default. National TB programmes might be more likely to achieve their control targets if they include interventions aimed at improving adherence and cure rates, by diagnosing and treating substance abuse concurrently with standard TB therapy.
Full Text Available Subacromial impingement syndrome (SIS is a very common cause of shoulder pain in the young adults. It can cause debilitating pain, dysfunction, and affects the activities of daily living. It represents a spectrum of pathology ranging from bursitis to rotator cuff tendinopathy which can ultimately lead to degenerative tear of the rotator cuff. Various theories and concepts have been described and it is still a matter of debate. However, most published studies suggest that both extrinsic and intrinsic factors have a role in the development of SIS. The management is controversial as both nonoperative and operative treatments have shown to provide good results. This article aims to provide a comprehensive current concepts review of the pathogenesis, etiologies, clinical diagnosis, appropriate use of investigations, and discussion on the management of SIS.
Kolontarev, Konstantin; Govorov, Alexander; Kasyan, George; Priymak, Diana; Pushkar, Dmitry
Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptom (LUTS) development in men . The intensity of the symptoms may vary from mild to severe, significantly affecting the quality of life. Erectile dysfunction (ED) is one of the most challenging issues in modern urology that significantly influences the quality of life in men worldwide. The objective of this literature review was to analyze the current drug therapies of patients with BPH-LUTS, with the special emphasis on PDE5 inhibitors. The authors searched the literature for the period from 2000 until 2015 in MEDLINE and PubMed. Twenty-three articles were selected based on their reliability. A detailed analysis of the selected papers was performed. Primary attention was given to articles describing the use of PDE5. Works describing the use of different groups of drugs in patients with BPH-LUTS were also selected. The current literature analysis suggests that the introduction of PDE5 inhibitors in clinical practice for the treatment of patients with BPH-LUTS will allow for significant expansion of the therapeutic options for the treatment of this disease.
Wu, Yan; Freed, Anita; Lavrich, David; Raghavachari, Ramesh; Huynh-Ba, Kim; Shah, Ketan; Alasandro, Mark
In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts.
The causes of drug abuse and criminal behavior are closely linked. Not surprisingly, there is a high percentage of prisoners who during sentence execution abuse or are dependent on drugs. Antisocial personality disorder can be considered a common predictor of committing criminal offenses and drug abuse. A review of studies has revealed a high prevalence of inmates who use drugs while serving a sentence. Also, prison environment represents only a new context of the continuum of drug abuse by i...
Perry, Jennifer L; Joseph, Jane E; Jiang, Yang; Zimmerman, Rick S; Kelly, Thomas H; Darna, Mahesh; Huettl, Peter; Dwoskin, Linda P; Bardo, Michael T
Vulnerability to drug abuse is related to both reward seeking and impulsivity, two constructs thought to have a biological basis in the prefrontal cortex (PFC). This review addresses similarities and differences in neuroanatomy, neurochemistry and behavior associated with PFC function in rodents and humans. Emphasis is placed on monoamine and amino acid neurotransmitter systems located in anatomically distinct subregions: medial prefrontal cortex (mPFC); lateral prefrontal cortex (lPFC); anterior cingulate cortex (ACC); and orbitofrontal cortex (OFC). While there are complex interconnections and overlapping functions among these regions, each is thought to be involved in various functions related to health-related risk behaviors and drug abuse vulnerability. Among the various functions implicated, evidence suggests that mPFC is involved in reward processing, attention and drug reinstatement; lPFC is involved in decision-making, behavioral inhibition and attentional gating; ACC is involved in attention, emotional processing and self-monitoring; and OFC is involved in behavioral inhibition, signaling of expected outcomes and reward/punishment sensitivity. Individual differences (e.g., age and sex) influence functioning of these regions, which, in turn, impacts drug abuse vulnerability. Implications for the development of drug abuse prevention and treatment strategies aimed at engaging PFC inhibitory processes that may reduce risk-related behaviors are discussed, including the design of effective public service announcements, cognitive exercises, physical activity, direct current stimulation, feedback control training and pharmacotherapies. A major challenge in drug abuse prevention and treatment rests with improving intervention strategies aimed at strengthening PFC inhibitory systems among at-risk individuals. Copyright © 2010 Elsevier B.V. All rights reserved.
Mitrzyk, Beatriz Manzor
Abstract Outbreaks of extensively drug-resistant tuberculosis (XDR-TB) in developing countries and recent headlines of an American traveling with a resistant variant of tuberculosis have brought XDR-TB into the spotlight. The World Health Organization and the United States Centers for Disease Control and Prevention have identified XDR-TB as a serious public health threat and are mandating increased efforts at control of tuberculosis. Although XDR-TB is believed to be no more infectious than other variants of tuberculosis, infection with and spread of XDR-TB are concerning because of the ineffectiveness, toxicity, and cost of the available tuberculosis treatment options. Pharmacists may not be aware of the recent trends in tuberculosis resistance or of the impact that they can have on educating the public about this disease. To gain a better understanding of this disease and the potential roles for pharmacists in public health awareness of tuberculosis and in the care of patients with and at risk for this disease, we undertook an extensive search of the Internet, including Web sites of tuberculosis advocacy groups, and of MEDLINE from January 1968-March 2008. Currently, XDR-TB infection is uncommon in the United States, but if history is any indication, there is a high potential for an outbreak or epidemic. The XDR-TB variant has emerged from mismanaging multidrug-resistant tuberculosis, treating tuberculosis with too few drugs, using less effective second-line drugs, and not educating patients about the dangers of nonadherence. With only limited hopes of a novel effective drug combination regimen, use of available antimycobacterial drugs needs to be optimized. Pharmacists can be key players in the prevention and treatment of tuberculosis by promoting adherence, assessing patients for risk factors for resistant disease, providing information about disease control and prevention, and monitoring for effectiveness, adverse effects, and drug interactions.
Bui, Anh D; Alexander, Allyson; Soltesz, Ivan
The unpredictability and severity of seizures contribute to the debilitating nature of epilepsy. These factors also render the condition particularly challenging to treat, as an ideal treatment would need to detect and halt the pathological bursts of hyperactivity without disrupting normal brain activity. Optogenetic techniques offer promising tools to study and perhaps eventually treat this episodic disorder by controlling specific brain circuits in epileptic animals with great temporal precision. Here, we briefly review the current treatment options for patients with epilepsy. We then describe the many ways optogenetics has allowed us to untangle the microcircuits involved in seizure activity, and how it has, in some cases, changed our perception of previous theories of seizure generation. Control of seizures with light is no longer a dream, and has been achieved in numerous different animal models of epilepsy. Beyond its application as a seizure suppressor, we highlight another facet of optogenetics in epilepsy, namely the ability to create "on-demand" seizures, as a tool to systematically probe the dynamics of networks during seizure initiation and propagation. Finally, we look into the future to discuss the possibilities and challenges of translating optogenetic techniques to clinical use. © The Author(s) 2015.
Full Text Available Alzheimer’s disease (AD currently presents one of the biggest healthcare issues in the developed countries. There is no effective treatment capable of slowing down disease progression. In recent years the main focus of research on novel pharmacotherapies was based on the amyloidogenic hypothesis of AD, which posits that the beta amyloid (Aβ peptide is chiefly responsible for cognitive impairment and neuronal death. The goal of such treatments is (a to reduce Aβ production through the inhibition of β and γ secretase enzymes and (b to promote dissolution of existing cerebral Aβ plaques. However, this approach has proven to be only modestly effective. Recent studies suggest an alternative strategy centred on the inhibition of the downstream Aβ signalling, particularly at the synapse. Aβ oligomers may cause aberrant N-methyl-D-aspartate receptor (NMDAR activation postsynaptically by forming complexes with the cell-surface prion protein (PrPC. PrPC is enriched at the neuronal postsynaptic density, where it interacts with Fyn tyrosine kinase. Fyn activation occurs when Aβ is bound to PrPC-Fyn complex. Fyn causes tyrosine phosphorylation of the NR2B subunit of metabotropic glutamate receptor 5 (mGluR5. Fyn kinase blockers masitinib and saracatinib have proven to be efficacious in treating AD symptoms in experimental mouse models of the disease.
Jarrett, D.G. [OSA - CBD and CDP, 3050 Defense Pentagon, Room 3C257, Washington, DC 20301-3050 (United States)], E-mail: firstname.lastname@example.org; Sedlak, R.G.; Dickerson, W.E. [Uniformed Services University, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States); Reeves, G.I. [Northrop Grumman IT, 8211 Terminal Road, Lorton, VA 22079-1421 (United States)
A nuclear incident or major release of radioactive materials likely would result in vast numbers of patients, many of whom would require novel therapy. Fortunately, the numbers of radiation victims in the United States (USA) have been limited to date. If a mass-casualty situation occurs, there will be a need to perform rapid, accurate dose estimates and to provide appropriate medications and other treatment to ameliorate radiation injury. The medical management of radiation injury is complex. Radiation injury may include acute radiation sickness (ARS) from external and/or internal radiation exposure, internal organ damage from incorporated radioactive isotopes, and cutaneous injury. Human and animal data have shown that optimal medical care may nearly double the survivable dose of ionizing radiation. Current treatment strategies for radiation injuries are discussed with concentration on the medical management of the hematopoietic syndrome. In addition, priority areas for continuing and future research into both acute deterministic injuries and also long-term stochastic sequelae of radiation exposure have been identified. There are several near-term novel therapies that appear to offer excellent prognosis for radiation casualties, and these are also described.
Mah, Jean K
Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the history and examination of affected boys presenting with developmental delay, proximal weakness, and elevated serum creatine kinase, plus confirmation by muscle biopsy or genetic testing. Precise characterization of the DMD mutation is important for genetic counseling and individualized treatment. Current standard of care includes the use of corticosteroids to prolong ambulation and to delay the onset of secondary complications. Early use of cardioprotective agents, noninvasive positive pressure ventilation, and other supportive strategies has improved the life expectancy and health-related quality of life for many young adults with DMD. New emerging treatment includes viral-mediated microdystrophin gene replacement, exon skipping to restore the reading frame, and nonsense suppression therapy to allow translation and production of a modified dystrophin protein. Other potential therapeutic targets involve upregulation of compensatory proteins, reduction of the inflammatory cascade, and enhancement of muscle regeneration. So far, data from DMD clinical trials have shown limited success in delaying disease progression; unforeseen obstacles included immune response against the generated mini-dystrophin, inconsistent evidence of dystrophin production in muscle biopsies, and failure to demonstrate a significant improvement in the primary outcome measure, as defined by the 6-minute walk test in some studies. The long-term safety and efficacy of emerging treatments will depend on the selection of appropriate clinical end points and sensitive biomarkers to detect meaningful changes in disease progression. Correction of the underlying
Nunn, Amy S; Fonseca, Elize M; Bastos, Francisco I; Gruskin, Sofia; Salomon, Joshua A
/r, efavirenz, tenofovir, atazanavir, enfuvirtide, and a locally produced generic, fixed-dose combination of zidovudine and lamivudine (AZT/3TC). Because prices declined for many of the patented drugs that constitute the largest share of drug costs, nearly the entire increase in overall drug expenditures between 2001 and 2005 is attributable to increases in drug quantities. Had all drug quantities been held constant from 2001 until 2005 (or for those drugs entering treatment guidelines after 2001, held constant between the year of introduction and 2005), total costs would have increased by only an estimated US$7 million. We estimate that in the absence of price declines for patented drugs, Brazil would have spent a cumulative total of US$2 billion on drugs for HAART between 2001 and 2005, implying a savings of US$1.2 billion from price declines. Finally, in comparing Brazilian prices for locally produced generic ARVs to the lowest international prices meeting global pharmaceutical quality standards, we find that current prices for Brazil's locally produced generics are generally much higher than corresponding global prices, and note that these prices have risen in Brazil while declining globally. We estimate the excess costs of Brazil's locally produced generics totaled US$110 million from 2001 to 2005. Despite Brazil's more costly generic ARVs, the net result of ARV price changes has been a cost savings of approximately US$1 billion since 2001. HAART costs have nevertheless risen steeply as Brazil has scaled up treatment. These trends may foreshadow future AIDS treatment cost trends in other developing countries as more people start treatment, AIDS patients live longer and move from first-line to second and third-line treatment, AIDS treatment becomes more complex, generic competition emerges, and newer patented drugs become available. The specific application of the Brazilian model to other countries will depend, however, on the strength of their health systems, intellectual
Amy S Nunn
: patented lopinavir/r, efavirenz, tenofovir, atazanavir, enfuvirtide, and a locally produced generic, fixed-dose combination of zidovudine and lamivudine (AZT/3TC. Because prices declined for many of the patented drugs that constitute the largest share of drug costs, nearly the entire increase in overall drug expenditures between 2001 and 2005 is attributable to increases in drug quantities. Had all drug quantities been held constant from 2001 until 2005 (or for those drugs entering treatment guidelines after 2001, held constant between the year of introduction and 2005, total costs would have increased by only an estimated US$7 million. We estimate that in the absence of price declines for patented drugs, Brazil would have spent a cumulative total of US$2 billion on drugs for HAART between 2001 and 2005, implying a savings of US$1.2 billion from price declines. Finally, in comparing Brazilian prices for locally produced generic ARVs to the lowest international prices meeting global pharmaceutical quality standards, we find that current prices for Brazil's locally produced generics are generally much higher than corresponding global prices, and note that these prices have risen in Brazil while declining globally. We estimate the excess costs of Brazil's locally produced generics totaled US$110 million from 2001 to 2005.Despite Brazil's more costly generic ARVs, the net result of ARV price changes has been a cost savings of approximately US$1 billion since 2001. HAART costs have nevertheless risen steeply as Brazil has scaled up treatment. These trends may foreshadow future AIDS treatment cost trends in other developing countries as more people start treatment, AIDS patients live longer and move from first-line to second and third-line treatment, AIDS treatment becomes more complex, generic competition emerges, and newer patented drugs become available. The specific application of the Brazilian model to other countries will depend, however, on the strength of their health
Maria Adriana Rangel
Full Text Available The authors present a case report of antituberculosis drug-induced liver injury that offered diagnostic challenges (namely, the possibility of drug-induced autoimmune hepatitis and treatment difficulties.
Zhang, Z.; Huang, G.
The objective of this paper is to provide readers with current developments of intra-articular drug delivery systems. In recent years, although the search for a clinically successful ideal carrier is ongoing, sustained-release systems, such as polymeric micro- and nanoparticles, liposomes, and hydrogels, are being extensively studied for intra-articular drug delivery purposes. The advantages associated with long-acting preparations include a longer effect of the drug in the action site and a reduced risk of infection due to numerous injections consequently. This paper discusses the recent developments in the field of intra-articular sustained-release delivery systems for the treatment of osteoarthritis
Full Text Available The objective of this paper is to provide readers with current developments of intra-articular drug delivery systems. In recent years, although the search for a clinically successful ideal carrier is ongoing, sustained-release systems, such as polymeric micro- and nanoparticles, liposomes, and hydrogels, are being extensively studied for intra-articular drug delivery purposes. The advantages associated with long-acting preparations include a longer effect of the drug in the action site and a reduced risk of infection due to numerous injections consequently. This paper discusses the recent developments in the field of intra-articular sustained-release delivery systems for the treatment of osteoarthritis.
Tutton, P J; Barkla, D H
A stathmokinetic technique was used to study cell proliferation in dimethylhydrazine-induced adenocarcinomata of rat colon following treatment with cytotoxic drugs. The rate of cell division was significantly increased three days after treatment with 5,7-dihydroxytryptamine and seven days after treatment with 5-fluorouracil. Acceleration of tumour cell proliferation following 5,7-dihydroxytryptamine treatment was inhibited by treating animals with the antiseritoninergic drug Xylamidine Tosylate. Acceleration of tumour cell proliferation following 5-fluorouracil treatment was inhibited by treating animals either with the antiseritoninergic drug BW501 or with the histamine H2-receptor blocking drug Cimetidine.
Urie, Marcia; FitzGerald, T.J.; Followill, David; Laurie, Fran; Marcus, Robert; Michalski, Jeff
Purpose: To report current technology implementation, radiation therapy physics and treatment planning practices, and results of treatment planning exercises among 261 institutions belonging to the Children's Oncology Group (COG). Methods and Materials: The Radiation Therapy Committee of the newly formed COG mandated that each institution demonstrate basic physics and treatment planning abilities by satisfactorily completing a questionnaire and four treatment planning exercises designed by the Quality Assurance Review Center. The planning cases are (1) a maxillary sinus target volume (for two-dimensional planning), (2) a Hodgkin's disease mantle field (for irregular-field and off-axis dose calculations), (3) a central axis blocked case, and (4) a craniospinal irradiation case. The questionnaire and treatment plans were submitted (as of 1/30/02) by 243 institutions and completed satisfactorily by 233. Data from this questionnaire and analyses of the treatment plans with monitor unit calculations are presented. Results: Of the 243 clinics responding, 54% use multileaf collimators routinely, 94% use asymmetric jaws routinely, and 13% use dynamic wedges. Nearly all institutions calibrate their linear accelerators following American Association of Physicists in Medicine protocols, currently 16% with TG-51 and 81% with TG-21 protocol. Treatment planning systems are relied on very heavily for all calculations, including monitor units. Techniques and results of each of the treatment planning exercises are presented. Conclusions: Together, these data provide a unique compilation of current (2001) radiation therapy practices in institutions treating pediatric patients. Overall, the COG facilities have the equipment and the personnel to perform high-quality radiation therapy. With ongoing quality assurance review, radiation therapy compliance with COG protocols should be high
T. S. Nepomnyashchikh
Full Text Available Over last decade, a substantial progress has been made, with respect to understanding of cancer biology and its interplay with the host immune system. Different immunotherapeutic drugs based on recombinant cytokines and monoclonal antibodies are widely used in cancer therapy, and a large number of experimental cancer treatments have been developed, many of which are currently undergoing various stages of clinical trials. Recent endorsement of a recombinant oncolytic herpesvirus T-VEC for the treatment of melanoma was an important step towards a more safe and efficient anticancer therapeutics. In this review, we shall mention only some of the most promising cancer immunotherapy strategies, namely, immune checkpoint inhibitors, cellular therapy and oncolytic viruses.
Polireddy, Kishore; Chen, Qi
Pancreatic cancer is one of the most lethal cancers among all malignances, with a median overall survival of cancers harbor a variety of genetic alternations that render it difficult to treat even with targeted therapy. Recent studies revealed that pancreatic cancers are highly enriched with a cancer stem cell (CSC) population, which is resistant to chemotherapeutic drugs, and therefore escapes chemotherapy and promotes tumor recurrence. Cancer cell epithelial to mesenchymal transition (EMT) is highly associated with metastasis, generation of CSCs, and treatment resistance in pancreatic cancer. Reviewed here are the molecular biology of pancreatic cancer, the major signaling pathways regulating pancreatic cancer EMT and CSCs, and the advancement in current clinical and experimental treatments for pancreatic cancer.
Hollon, Matthew F
In the US and New Zealand, the past decade has seen tremendous growth in the marketing of prescription drugs directly to patients. The pharmaceutical industry has applied pressure in other countries to relax regulations governing such marketing although this has not yet been successful. While we still have much to learn about the potential impact on the public's health of direct-to-consumer (DTC) marketing, some data are available. This article summarises the current literature on the benefits and risks of DTC marketing. This marketing strategy has grown substantially in the US, but only select drugs are advertised. Whether there is net benefit or harm to the public's health as a result of DTC marketing depends critically on which drugs are advertised and the quality of the information provided in promotional material. Critical reviews of this promotional material suggest the information is of poor quality. Notably, 18% of the 50 drugs advertised most intensively in the US were medications used to treat psychiatric and neurological disorders. The impairments in decisional capacity often seen in psychiatric and neurological illness leave patients vunerable to the controlling influence of DTC marketing and, thus, undermine the patient autonomy that is said to be promoted by this marketing strategy. If there is any benefit from DTC marketing it is for significantly undertreated conditions. International restrictions on DTC marketing should remain in place until further evidence of net benefit or harm emerges from the DTC marketing experiment that is taking place in the US and New Zealand.
Reynoso-Vallejo, Humberto; Chassler, Deborah; Witas, Julie; Lundgren, Lena M
This study examined patterns of treatment entry by Puerto Rican, Central American, Dominican, and other Latino male injection drug users (IDUs) in the state of Massachusetts over the time period 1996-2002. Specifically, it explored whether these populations had different patterns relative to three paths: entry into detoxification only, entry into residential treatment, or entry into methadone maintenance. Using a state-level MIS dataset on all substance abuse treatment entries to all licensed treatment programs, bi-variate and logistic regression methods were employed to examine patterns of drug treatment utilization among Latino men residing in Massachusetts. Three logistic regression models, which controlled for age, education, homelessness, employment, history of mental health treatment, health insurance, criminal justice involvement, having injected drugs in the past month, and number of treatment entries, indicated that Puerto Rican men were significantly less likely to only use detoxification services and residential treatment services, and significantly more likely to enter methadone maintenance compared to Latino men from Central American, Dominican, or other Latino backgrounds. For example, Central American men were 2.4 times more likely to enter only detoxification programs and 54% less likely to enter methadone maintenance programs than Puerto Rican male IDUs. For program planning, include the need to (a) develop varied drug treatment services to meet the needs of non-homogenous Latino groups within the population, (b) tailor outreach efforts to effectively reach all Latino groups, and (c) increase awareness among practitioners of differential patterns of treatment utilization.
Duley, Lelia; Meher, Shireen; Jones, Leanne
, 1650 women; 47% versus 65%; RR 0.84, 95% CI 0.76 to 0.93). Nimodipine was associated with a lower risk of respiratory difficulties (RR 0.28, 95% CI 0.08 to 0.99), fewer side-effects (RR 0.68, 95% CI 0.55 to 0.85) and less postpartum haemorrhage (RR 0.41, 95% CI 0.18 to 0.92) than magnesium sulphate. Stillbirths and neonatal deaths were not reported.There are insufficient data for reliable conclusions about the comparative effects of any other drugs. Until better evidence is available the choice of antihypertensive should depend on the clinician's experience and familiarity with a particular drug; on what is known about adverse effects; and on women's preferences. Exceptions are nimodipine, magnesium sulphate (although this is indicated for women who require an anticonvulsant for prevention or treatment of eclampsia), diazoxide and ketanserin, which are probably best avoided.
Full Text Available Subhajit Das, Julie C Crockett Musculoskeletal Research Programme, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK Abstract: Postmenopausal osteoporosis is the most common bone disease, associated with low bone mineral density (BMD and pathological fractures which lead to significant morbidity. It is defined clinically by a BMD of 2.5 standard deviations or more below the young female adult mean (T-score = −2.5. Osteoporosis was a huge global problem both socially and economically – in the UK alone, in 2011 £6 million per day was spent on treatment and social care of the 230,000 osteoporotic fracture patients – and therefore viable preventative and therapeutic approaches are key to managing this problem within the aging population of today. One of the main issues surrounding the potential of osteoporosis management is diagnosing patients at risk before they develop a fracture. We discuss the current and future possibilities for identifying susceptible patients, from fracture risk assessment to shape modeling and in relation to the high heritability of osteoporosis now that a plethora of genes have been associated with low BMD and osteoporotic fracture. This review highlights the current therapeutics in clinical use (including bisphosphonates, anti-RANKL [receptor activator of NF-κB ligand], intermittent low dose parathyroid hormone, and strontium ranelate and some of those in development (anti-sclerostin antibodies and cathepsin K inhibitors. By highlighting the intimate relationship between the activities of bone forming (osteoblasts and bone-resorbing (osteoclasts cells, we include an overview and comparison of the molecular mechanisms exploited in each therapy. Keywords: BMD, fracture, bisphosphonate, strontium, denosumab, teriparatide, raloxifene
Full Text Available Jiedi Lei, Pamela Ventola Yale Child Study Center, Yale University School of Medicine, New Haven, CT, USA Abstract: Pivotal response treatment (PRT is an evidence-based behavioral intervention based on applied behavior analysis principles aimed to improve social communication skills in individuals with autism spectrum disorder (ASD. PRT adopts a more naturalistic approach and focuses on using a number of strategies to help increase children’s motivation during intervention. Since its conceptualization, PRT has received much empirical support for eliciting therapeutic gains in greater use of functional social communication skills in individuals with ASD. Building upon the empirical evidence supporting PRT, recent advancements have increasingly turned to using interdisciplinary research integrating neuroimaging techniques and behavioral measures to help identify objective biomarkers of treatment, which have two primary purposes. First, neuroimaging results can help characterize how PRT may elicit change, and facilitate partitioning of the heterogeneous profiles of neural mechanisms underlying similar profile of behavioral changes observed over PRT. Second, neuroimaging provides an objective means to both map and track how biomarkers may serve as reliable and sensitive predictors of responder profiles to PRT, assisting clinicians to identify who will most likely benefit from PRT. Together, a better understanding of both mechanisms of change and predictors of responder profile will help PRT to serve as a more precise and targeted intervention for individuals with ASD, thus moving towards the goal of precision medicine and improving quality of care. This review focuses on the recent emerging neuroimaging evidences supporting PRT, offering current perspectives on the importance of interdisciplinary research to help clinicians better understand how PRT works and predict who will respond to PRT. Keywords: PRT, ASD, biomarkers, neuroimaging
Ciurba, Adriana; Todoran, Nicoleta; Vari, C E; Lazăr, Luminita; Al Hussein, Stela; Hancu, G
The current trend of replacing conventional pharmaceutical forms is justified because most substances administered in this form give fluctuations of therapeutic concentrations and often outside the therapeutic range. In addition, these formulations offer a reduction in the dose or the number of administrations, thus increasing patient compliance. In the experiment, we developed an appropriate technology for the preparation of gelatin microspheres containing tramadol hydrochloride by emulsification/cross-linking method. The formulated microspheres were characterized by product yield, size distribution, encapsulation efficiency and in vitro release of tramadol hydrochloride. Data obtained from in vitro release studies were fitted to various mathematical models to elucidate the transport mechanisms. The kinetic models used were zero-order, first-order, Higuchi Korsmeyer-Peppas and Hopfenberg. Spherical microspheres were obtained, with free-flowing properties. The entrapment efficiency of tramadol hydrochloride in microparticles was 79.91% and product yield -94.92%. As the microsphere size was increased, the entrapment efficiency increased. This was 67.56, 70.03, 79.91% for formulations MT80-250, MT8-500 and, MT250-500. High entrapment efficiency was observed for MT250-500 formulation. The gelatin microspheres had particle sizes ranging from 80 to 500 microm. The drug was released for a period of 12 hours with a maximum release of 96.02%. Of the three proposed formulations, MT250-500 presented desirable properties and optimal characteristics for the therapy of pain. Release of tramadol hydrochloridi was best fitted to Korsmeyer-Peppas equation because the Akaike Information Criterion had the lowest values for this kinetic model. These results suggest the opportunity to influence the therapeutic characteristics of gelatin microspheres to obtain a suitable drug delivery system for the oral administration of tramadol hydrochloride.
Ikeda, Y.; Hirayama, T.; Terada, K.
The thermal stimulated current measurement was used as an innovative analytical equipment to evaluate the polymorphic properties of terfenadine and Compound A, being developed by Takeda Pharmaceutical Company, Limited. At first, terfenadine, which is known to have polymorphs, was used as a model sample for thermally stimulated current (TSC) analyses. The TSC curves of amorphous and two polymorphs were distinctly different from each other. Therefore, it was considered that TSC measurement could be a useful technique to evaluate the crystalline properties of drug substances. The polymorphs of compound A were difficult to distinguish the characteristics of polymorphs from conventional powder X-ray diffractometry and also differential scanning calorimetry. Forms A and B of compound A were clearly differentiated by the thermal stimulated current properties that were adequate to characterize each form. Thus, it was shown that TSC was extremely useful and powerful tool for identification of complicated polymorphs, which were not distinguished by conventional methods
Tfelt-Hansen, Peer; Ågesen, Frederik Nybye; Pavbro, Agniezka
In this review, we evaluate the variability in the pharmacokinetics of 11 drugs with established prophylactic effects in migraine to facilitate 'personalized medicine' with these drugs. PubMed was searched for 'single-dose' and 'steady-state' pharmacokinetic studies of these 11 drugs. The maximum...
Object Preterm infants are at risk for perinatal complications, including germinal matrix–intraventricular hemorrhage (IVH) and subsequent posthemorrhagic hydrocephalus (PHH). This review summarizes the current understanding of the epidemiology, pathophysiology, management, and outcomes of IVH and PHH in preterm infants. Methods The MEDLINE database was systematically searched using terms related to IVH, PHH, and relevant neurosurgical procedures to identify publications in the English medical literature. To complement information from the systematic search, pertinent articles were selected from the references of articles identifed in the initial search. Results This review summarizes the current knowledge regarding the epidemiology and pathophysiology of IVH and PHH, primarily using evidence-based studies. Advances in obstetrics and neonatology over the past few decades have contributed to a marked improvement in the survival of preterm infants, and neurological morbidity is also starting to decrease. The incidence of IVH is declining, and the incidence of PHH will likely follow. Currently, approximately 15% of preterm infants who suffer severe IVH will require permanent CSF diversion. The clinical presentation and surgical management of symptomatic PHH with temporary ventricular reservoirs (ventricular access devices) and ventriculosubgaleal shunts and permanent ventriculoperitoneal shunts are discussed. Preterm infants who develop PHH that requires surgical treatment remain at high risk for other related neurological problems, including cerebral palsy, epilepsy, and cognitive and behavioral delay. This review highlights numerous opportunities for further study to improve the care of these children. Conclusions A better grasp of the pathophysiology of IVH is beginning to impact the incidence of IVH and PHH. Neonatologists conduct rigorous Class I and II studies to advance the outcomes of preterm infants. The need for well-designed multicenter trials is
Nielsen, René Ernst; Nielsen, Jimmi
The cornerstone in treatment of psychosis is antipsychotic drugs. Treatment options have increased over the years; newer antipsychotic drugs with a proposed efficacy regarding negative and cognitive symptoms, but also a shift in side-effects from neurological side-effects to metabolic side......-effects have arisen as the new challenge. The basis of successful pharmacological treatment is a fundamental understanding of the mechanisms of action, the desired effects and side-effects of antipsychotic drugs, a good relationship with the patient and a thorough monitoring of the patient before and during...... treatment. The clinically relevant aspects of antipsychotic drug treatment are reviewed; mechanism of antipsychotic drug action, clinical considerations in treatment, switching antipsychotic drugs, polypharmacy, safety and patient preference. ...
Yu. G. Alyaev
Full Text Available Most patients lower urinary tract symptoms (LUTS caused both mechanical and functional factors. Timely identification of the nature of urodynamics, primarily of bladder outlet obstruction and detrusor overactivity, in patients with benign prostatic hyperplasia is of practical importance, since without this factor significantly worse functional outcome of surgical treatment. α1-adrenoblockers are the first line therapy for men with bothersome LUTS. They should be offered to patients with moderate to severe LUTS. Choosing α1-adrenoblocker should lean toward more selective class representatives. Selectivity α1-adrenoblocker provides high efficiency along with a low percentage of adverse effects, especially for cardiovascular system.As well as α-adrenoblockers, M-cholinobloсkers varying degrees of selectivity of the impact is on the bladder. Solifenacin is more selective for the bladder than tolterodine and oxybutynin. The selectivity of the drug with respect to the bladder is reflected in the relatively low frequency of adverse effects, especially occurrence of dry mouth in its application, as well as the possibility of long term therapy. Combined treatment with α1-adrenoreceptor antagonist with M-cholinergic antagonists may be considered in patients with moderate to severe LUTS with a predominance of filling symptoms, especially if monotherapy led to relief of symptoms.
Wong, Trisha; Recht, Michael
Haemophilia A and B are X-linked bleeding disorders due to the inherited deficiency of factor VIII or factor IX, respectively. Of the approximately 1 per 5000-10000 male births affected by haemophilia, 80% are deficient in factor VIII and 20% are deficient in factor IX. Haemophilia is characterized by spontaneous and provoked joint, muscle, gastrointestinal and CNS bleeding leading to major morbidity and even mortality if left untreated or under-treated. The evolution of haemophilia management has been marked by tragedy and triumph over recent decades. Clotting factors and replacement strategies continue to evolve for patients without inhibitors. For patients with an inhibitor, factor replacement for acute bleeding episodes and immune tolerance, immune modulation and extracorporeal methods for inhibitor reduction are the cornerstone of care. In addition, adjuvant therapies such as desmopressin, antifibrinolytics and topical agents also contribute to improved outcomes for patients with and without inhibitors. The future direction of haemophilia care is promising with new longer-acting clotting factors and genetic therapies, including gene transfer and premature termination codon suppressors. With these current and future treatment modalities, the morbidity and mortality rates in patients with haemophilia certainly will continue to improve.
Mathews, Patrick D; Fernandes Patta, Ana C M; Gonçalves, Joao V; Gama, Gabriella Dos Santos; Garcia, Irene Teresinha Santos; Mertins, Omar
Biomaterials conceived for vectorization of bioactives are currently considered for biomedical, biological, and environmental applications. We have produced a pH-sensitive biomaterial composed of natural source alginate and chitosan polysaccharides for application as a drug delivery system via oral administration. The composite particle preparation was in situ monitored by means of isothermal titration calorimetry. The strong interaction established between the macromolecules during particle assembly led to 0.60 alginate/chitosan effective binding sites with an intense exothermic effect and negative enthalpy variation on the order of a thousand kcal/mol. In the presence of model drugs mebendazole and ivermectin, with relatively small and large structures, respectively, mebendazole reduced the amount of chitosan monomers available to interact with alginate by 27%, which was not observed for ivermectin. Nevertheless, a state of intense negative Gibbs energy and large entropic decrease was achieved, providing evidence that formation of particles is thermodynamically driven and favored. Small-angle X-ray scattering provided further evidence of similar surface aspects independent of the presence of drug. The physical responses of the particles to pH variation comprise partial hydration, swelling, and the predominance of positive surface charge in strong acid medium, whereas ionization followed by deprotonation leads to compaction and charge reversal rather than new swelling in mild and slightly acidic mediums, respectively. In vivo performance was evaluated in the treatment of endoparasites in Corydoras fish. Systematically with a daily base oral administration, particles significantly reduced the infections over 15 days of treatment. The experiments provide evidence that utilizing particles granted and boosted the action of the antiparasitic drugs, leading to substantial reduction or elimination of infection. Hence, the pH-responsive particles represent a biomaterial
Palleria, Caterina; Leporini, Christian; Maida, Francesca; Succurro, Elena; De Sarro, Giovambattista; Arturi, Franco; Russo, Emilio
Type 2 diabetes mellitus is a complex metabolic disease that can cause serious damage to various organs. Among the best-known complications, an important role is played by cognitive impairment. Impairment of cognitive functioning has been reported both in type 1 and 2 diabetes mellitus. While this comorbidity has long been known, no major advances have been achieved in clinical research; it is clear that appropriate control of blood glucose levels represents the best current (although unsatisfactory) approach in the prevention of cognitive impairment. We have focused our attention on the possible effect on the brain of antidiabetic drugs, despite their effects on blood glucose levels, giving a brief rationale on the mechanisms (e.g. GLP-1, BDNF, ghrelin) that might be involved. Indeed, GLP-1 agonists are currently clinically studied in other neurodegenerative diseases (i.e. Parkinson's and Alzheimer's disease); furthermore, also other antidiabetic drugs have proven efficacy in preclinical studies. Overall, promising results are already available and finding new intervention strategies represents a current need in this field of research. Copyright © 2016 Elsevier Inc. All rights reserved.
Full Text Available Genetic and genome-wide RNAi approaches available in C. elegans, combined with tools for visualizing subcellular events with high-resolution, have led to increasing adoption of the early C. elegans embryo as a model for mechanistic and functional genomic analysis of cellular processes. However, a limitation of this system has been the impermeability of the embryo eggshell, which has prevented the routine use of small molecule inhibitors. Here, we present a method to permeabilize and immobilize embryos for acute inhibitor treatment in conjunction with live imaging. To identify a means to permeabilize the eggshell, we used a dye uptake assay to screen a set of 310 candidate genes defined by a combination of bioinformatic criteria. This screen identified 20 genes whose inhibition resulted in >75% eggshell permeability, and 3 that permeabilized embryos with minimal deleterious effects on embryo production and early embryonic development. To mount permeabilized embryos for acute drug addition in conjunction with live imaging, we combined optimized inhibition of one of these genes with the use of a microfabricated chamber that we designed. We demonstrate that these two developments enable the temporally controlled introduction of inhibitors for mechanistic studies. This method should also open new avenues of investigation by allowing profiling and specificity-testing of inhibitors through comparison with genome-wide phenotypic datasets.
Yandrapalli, Srikanth; Pal, Suman; Nabors, Christopher; Aronow, Wilbert S
Hypertension is more prevalent in the elderly (age>65 years) diabetic population than in the general population and shows an increasing prevalence with advancing age. Both diabetes mellitus (DM) and hypertension are independent risk factors for cardiovascular (CV) related morbidity and mortality. Optimal BP targets were not identified in elderly patients with DM and hypertension. Areas covered: In this review article, the authors briefly discuss the pathophysiology of hypertension in elderly diabetics, present evidence with various antihypertensive drug classes supporting the treatment of hypertension to reduce CV events in older diabetics, and then discuss the optimal target BP goals in these patients. Expert opinion: Clinicians should have a BP goal of less than 130/80 mm in all elderly patients with hypertension and DM, especially in those with high CV-risk. When medications are required for optimal BP control in addition to lifestyle measures, either thiazide diuretics, angiotensin-converting-enzyme inhibitors, angiotensin receptor blockers, or calcium channel blockers should be considered as initial therapy. Combinations of medications are usually required in these patients because BP control is more difficult to achieve in diabetics than those without DM.
Chappel, E.; Dumont-Fillon, D.; Mefti, S.
Passive flow regulators are usually intended to deliver or drain a fluid at a constant rate independently from pressure variations. New designs of passive flow regulators made of a stack of a silicon membrane anodically bonded to a Pyrex substrate are proposed. A first design has been built for the derivation of cerebrospinal fluid (CSF) towards peritoneum for hydrocephalus treatment. The device allows draining CSF at the patient production rate independently from postural changes. The flow rate is regulated at 20 ml/h in the range 10 to 40 mbar. Specific features to adjust in vivo the nominal flow rate are shown. A second design including high pressure shut-off feature has been made. The intended use is drug delivery with pressurized reservoir of typically 100 to 300 mbar. In both cases, the membrane comprises several holes facing pillars in the Pyrex substrate. These pillars are machined in a cavity which ensures a gap between the membrane and the pillars at rest. The fluid in the pressurized reservoir is directly in contact with the top surface of the membrane, inducing its deflection towards Pyrex substrate and closing progressively the fluidic pathway through each hole of the membrane. Since the membrane deflection is highly non-linear, FEM simulations have been performed to determine both radial position and diameter of the membrane holes that ensure a constant flow rate for a given range of pressure.
At the seven-year anniversary of the first catheter-based renal denervation procedure for resistant hypertension, it is timely to reflect on the past, present, and future of the development and clinical application of this treatment. Unresolved procedural and technical questions are central: How much renal denervation is optimal? How can this level of denervation be achieved? What test for denervation can be applied in renal denervation trials? Will renal denervation show a "class effect," with the different energy forms now used for renal nerve ablation producing equivalent blood pressure lowering? When I have assessed renal denervation efficacy, using measurements of the spillover of norepinephrine from the renal sympathetic nerves to plasma, the only test validated to this point, denervation was found to be incomplete and non-uniform between patients. It is probable that the degree of denervation has commonly been suboptimal in renal denervation trials; this criticism applying with special force to the Symplicity HTN-3 trial, where the proceduralists, although expert interventional cardiologists, had no prior experience with the renal denervation technique. Recently presented results from the Symplicity HTN-3 trial confirm that renal denervation was not achieved effectively or consistently. Given this, and other difficulties in the execution of the trial relating to drug adherence, an idea mooted is that the US pivotal trial of the future may be in younger, untreated patients. Copyright © 2015 Elsevier Inc. All rights reserved.
receptors blocker, rimonabant. As for non-pharmaceutical treatments, medical advice is a useful tool whose success can range from 2 to 4%, but only 35% of medical professionals provide it (RM 1.74, IC95% 1.48-2.05. Group psychological therapy helps to modify the perception of cigarettes and its noxious effects. The success of this modality is between 20% and 35% per year (RM 2.17, IC95% 1.42-3.45. Some of the disadvantages are the time invested and the cost of the treatment, which can be considerable. Finally, self-help materials can increase success (RM 1.24, IC95% 1.07-1.45. In summary, multiple modalities currently exist that have been proven effective in the treatment for quitting smoking; however, the treatment should be individualized according to each particular case.
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Objective: Investigations of injecting drug users (IDUs have suggested that the social context may influence high-risk behaviours in this population. The aim of this study was to describe knowledge, attitudes and behaviours of IDUs attending public drug-treatment centres in our area.
Study design and methods: A cross-sectional survey was conducted between July 2002 and February 2004, enrolling 607 drug users attending four public drug-treatment centres in the Palermo area. Two of them were located inside the urban area, whereas the other two were in rural districts near the city. All participants answered an anonymous questionnaire concerning social and demographic characteristic and potential high-risk behaviours.
Results: IDUs living in urban context have a higher educational level, higher number of sexual partners, as well as a lower prevalence of exchanging sex for drugs. Conversely, IDUs living in suburban/rural context are less likely to share syringes and more likely to have used light drugs in the past. Suburban/rural IDUs drink more alcohol but smoke less cigarettes/day, although both groups are strong smokers.
Conclusions: The results suggest that public drug-treatment centres should take in consideration the adoption of specific programs targeting specific groups, in line with the profile and needs of the subjects in each context in order to promote approaches leading to risk reduction.
Tran, Bach Xuan
Willingness to pay for methadone maintenance treatment (MMT) in three Vietnamese epicentres of injection-drug-driven human immunodeficiency virus (HIV) infection was assessed. A convenience sample of 1016 patients receiving HIV treatment in seven clinics was enrolled during 2012. Contingent valuation was used to assess willingness to pay. Interviewers reviewed adverse consequences of injection drug use and the benefits of MMT. Interviewers then described the government's plan to scale up MMT and the financial barriers to scale-up. Willingness to pay was assessed using double-bounded binary questions and a follow-up open-ended question. Point and interval data models were used to estimate maximum willingness to pay. A total of 548 non-drug-users and 468 injection drug users were enrolled; 988 were willing to pay for MMT. Monthly mean willingness to pay among non-drug-users, 347 drug users not receiving MMT and 121 drug users receiving MMT was 10.7 United States dollars [US$] (35.7% of treatment costs), US$ 21.1 (70.3%) and US$ 26.2 (87.3%), respectively (mean: US$ 15.9; 95% confidence interval, CI: 13.6-18.1). Fifty per cent of drug users were willing to pay 50% of MMT costs. Residence in households with low monthly per capita income and poor health status predicted willingness to pay less among drug users; educational level, employment status, health status and current antiretroviral therapy receipt predicted willingness to pay less among non-drug-users. Willingness to pay for MMT was very high, supporting implementation of a co-payment programme.
Myasthenia gravis is an autoimmune neuromuscular disorder. There are several treatment options, including symptomatic treatment (acetylcholinesterase inhibitors), short-term immunosuppression (corticosteroids), long-term immunosuppression (azathioprine, cyclosporine, cyclophosphamide, methotrexate, mycophenolate mofetil, rituximab, tacrolimus), rapid acting short-term immunomodulation (intravenous immunoglobulin, plasma exchange), and long-term immunomodulation (thymectomy). This review explores in detail these different treatment options. Potential future treatments are also discussed. PMID:21845054
Asija Rajesh; Chaudhari Bharat; Asija Sangeeta
Small intestine is mostly the site for drug absorption but in some cases the drug needs to be targeted to colon due to some factors like local colonic disease, degradation related conditions, delayed release of drugs, systemic delivery of protein and peptide drugs etc. Colon targeted drug delivery is important and relatively new concept for the absorption of drugs because it offers almost neutral pH and long residence time, thereby increasing the drug absorption. Colon has proved to be a site...
Full Text Available Continued discovery and development of new antiviral medications are paramount for global human health, particularly as new pathogens emerge and old ones evolve to evade current therapeutic agents. Great success has been achieved in developing effective therapies to suppress human immunodeficiency virus (HIV and hepatitis B virus (HBV; however, the therapies are not curative and therefore current efforts in HIV and HBV drug discovery are directed toward longer-acting therapies and/or developing new mechanisms of action that could potentially lead to cure, or eradication, of the virus. Recently, exciting early clinical data have been reported for novel antivirals targeting respiratory syncytial virus (RSV and influenza (flu. Preclinical data suggest that these new approaches may be effective in treating high-risk patients afflicted with serious RSV or flu infections. In this review, we highlight new directions in antiviral approaches for HIV, HBV, and acute respiratory virus infections.
Sehgal, Sheikh Arslan; Hammad, Mirza A; Tahir, Rana Adnan; Akram, Hafiza Nisha; Ahmad, Faheem
As the number of elderly persons increases, neurodegenerative diseases are becoming ubiquitous. There is currently a great need for knowledge concerning management of old-age neurodegenerative diseases; the most important of which are: Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, and Huntington's disease. To summarize the potential of computationally predicted molecules and targets against neurodegenerative diseases. Review of literature published since 1997 against neurodegenerative diseases, utilizing as keywords: in silico, Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis ALS, and Huntington's disease. Due to the costs associated with experimentation and current ethical law, performing experiments directly on living organisms has become much more difficult. In this scenario, in silico techniques have been successful and have become powerful tools in the search to cure disease. Researchers use the Computer Aided Drug Design pipeline which: 1) generates 3-dimensional structures of target proteins through homology modeling 2) achieves stabilization through molecular dynamics simulation, and 3) exploits molecular docking through large compound libraries. Next generation sequencing is continually producing enormous amounts of raw sequence data while neuroimaging is producing a multitude of raw image data. To solve such pressing problems, these new tools and algorithms are required. This review elaborates precise in silico tools and techniques for drug targets, active molecules, and molecular docking studies, together with future prospects and challenges concerning possible breakthroughs in Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis, and Huntington's disease. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Full Text Available Obesity is a disease with pandemic frequency, often accompanied by chronic metabolic and organic complications. Type 2 diabetes mellitus (T2DM is among the most common metabolic complications of obesity. The first step in the treatment of T2DM is medical nutrition therapy combined with moderate physical activity and with advice to patients to reduce their body weight. Pharmacotherapy starts with metformin, and in the case of inadequate therapeutic response, another antihyperglycemic agent should be added. The most clinical experience exists with sulfonylurea agents, but their use is limited due to high incidence of hypoglycemia and increase in body weight. Based on the fact that dysfunction of adipose tissue can lead to the development of chronic degenerative complications, precise use of drugs with a favorable effect on the functionality of adipose tissue represents an imperative of modern T2DM treatment. Antihyperglycemic drugs of choice in obese individuals are those which cause maturation of adipocytes, improvement of secretion of protective adipokines, and redistribution of fat mass from visceral to subcutaneous depots. Oral antihyperglycemic agents that can affect the functionality of adipose tissue are metformin, SGLT-2 inhibitors, DPP-4 inhibitors, and thiazolidinediones.
Dencker, Ditte; Thomsen, Morgane; Wörtwein, Gitta
's disease and drug abuse. Dopaminergic systems are regulated by cholinergic, especially muscarinic, input. Not surprisingly, increasing evidence implicates muscarinic acetylcholine receptor-mediated pathways as potential targets for the treatment of these disorders classically viewed as "dopamine based...... site. Such agents may lead to the development of novel classes of drugs useful for the treatment of psychosis, drug abuse and Parkinson's disease. The present review highlights recent studies carried out using muscarinic receptor knock-out mice and new subtype-selective allosteric ligands to assess...... the roles of M(1), M(4), and M(5) receptors in various central processes that are under strong dopaminergic control. The outcome of these studies opens new perspectives for the use of novel muscarinic drugs for several severe disorders of the CNS....
By identifying some of the social correlates linked with completing day-care drug abuse treatment, the present study has sought to broaden understanding of how drug rehabilitations are effected. As the findings have demonstrated, completing care is a result of a complex array of causes and their interaction. The disposition of the entering patient (i.e., their determination and other strengths) has a great bearing on treatment outcome. It is also a result of the patient's family, their motivations, resources and perseverance in enduring a long course of demanding therapeutic interventions. In addition, it is the product of meanings shared and transmitted between the patient's family and the treatment staff. Patients and their families project positive attitudes about the value of the therapeutic enterprise as well as a compliant demeanor. As staff recognize that patients and parents are acting cooperatively, then such perceptions tend to create self-fulfilling prophecies. The data has established that older adolescent patients are more likely to possess the motivational resources needed for program completion than younger patients. Apparently, self-referred patients are also more inclined to meet the demands of program requirements than those referred by the courts or other outside social agencies, although the differences fell short of the .05 level of statistical significance. Those completing the program are less likely to be diagnosed as depressed at intake. Parental characteristics comprise another group of variables that are related to treatment completion. Parents of higher occupational rank, who have had mental health care for themselves, and who are of Jewish ethnicity appear to possess useful strengths for meeting program challenges. The pattern of spouse mutuality in dealing with a child's needs as it exists preceding and during treatment seems to be another useful asset for successfully getting through this form of treatment. While parents with the
Zurita, Florentina; Roy, Eric D; White, John R
The aim of this paper is to evaluate the current status of municipal wastewater (MWW) treatment in Mexico, as well as to assess opportunities for using ecological treatment systems, such as constructed wetlands. In 2008, Mexico had 2101 MWW treatment plants that treated only 84 m3/s of wastewater (208 m3/s ofMWW were collected in sewer systems). Unfortunately, most treatment plants operate below capacity owing to a lack of maintenance and paucity of properly trained personnel. The main types of treatment systems applied in Mexico are activated sludge and waste stabilization ponds, which treat 44.3% and 18% of the MWW collected, respectively. As in many other developing nations around the world, there is a great need in Mexico for low-cost, low-maintenance wastewater treatment systems that are both economically and environmentally sustainable. In 2005, 24.3 million Mexicans lived in villages of less than 2500 inhabitants and 14.1 million lived in towns with 2500-15,000 inhabitants. An opportunity exists to extend the use of ecological treatment systems to these low population density areas and considerably increase the percentage of MWW that is treated in Mexico. Small-scale and medium-size constructed wetlands have been built successfully in some states, primarily during the past five years. Several barriers need to be overcome to increase the adoption and utilization of ecological wastewater technology in Mexico, including: a lack of knowledge about this technology, scarce technical information in Spanish, and the government's concentration on constructing MWW treatment plants solely in urban areas.
Spiliotopoulou, Eirini; Boni, Maciej F; Yadav, Prashant
The efficacy of scarce drugs for many infectious diseases is threatened by the emergence and spread of resistance. Multiple studies show that available drugs should be used in a socially optimal way to contain drug resistance. This paper studies the tradeoff between risk of drug resistance and operational costs when using multiple drugs for a specific disease. Using a model for disease transmission and resistance spread, we show that treatment with multiple drugs, on a population level, results in better resistance-related health outcomes, but more interestingly, the marginal benefit decreases as the number of drugs used increases. We compare this benefit with the corresponding change in procurement and safety stock holding costs that result from higher drug variety in the supply chain. Using a large-scale simulation based on malaria transmission dynamics, we show that disease prevalence seems to be a less important factor when deciding the optimal width of drug assortment, compared to the duration of one episode of the disease and the price of the drug(s) used. Our analysis shows that under a wide variety of scenarios for disease prevalence and drug cost, it is optimal to simultaneously deploy multiple drugs in the population. If the drug price is high, large volume purchasing discounts are available, and disease prevalence is high, it may be optimal to use only one drug. Our model lends insights to policy makers into the socially optimal size of drug assortment for a given context.
Full Text Available Suganthini Krishnan Natesan,1,2 Pranatharthi H Chandrasekar1 1Division of Infectious Diseases, Department of Internal Medicine, Wayne State University, 2John D Dingell VA Medical Center, Detroit, MI, USA Abstract: The majority of invasive mold infections diagnosed in immunocompromised cancer patients include invasive aspergillosis (IA and mucormycosis. Despite timely and effective therapy, mortality remains considerable. Antifungal agents currently available for the management of these serious infections include triazoles, polyenes, and echinocandins. Until recently, posaconazole has been the only triazole with a broad spectrum of anti-mold activity against both Aspergillus sp. and mucorales. Other clinically available triazoles voriconazole and itraconazole, with poor activity against mucorales, have significant drug interactions in addition to a side effect profile inherent for all triazoles. Polyenes including lipid formulations pose a problem with infusion-related side effects, electrolyte imbalance, and nephrotoxicity. Echinocandins are ineffective against mucorales and are approved as salvage therapy for refractory IA. Given that all available antifungal agents have limitations, there has been an unmet need for a broad-spectrum anti-mold agent with a favorable profile. Following phase III clinical trials that started in 2006, isavuconazole (ISZ seems to fit this profile. It is the first novel triazole agent recently approved by the United States Food and Drug Administration (FDA for the treatment of both IA and mucormycosis. This review provides a brief overview of the salient features of ISZ, its favorable profile with regard to spectrum of antifungal activity, pharmacokinetic and pharmacodynamic parameters, drug interactions and tolerability, clinical efficacy, and side effects. Keywords: isavuconazole, aspergillosis, mucormycosis, efficacy, antifungal therapy, novel azole, tolerability, drug interactions
Adamson, T A; Onifade, P O; Ogunwale, A
Globally, patterns of the use of psychoactive substances have been changing. To evaluate the trend in two five year periods, 1992 to 1997 versus 2002 to 2007, of alcohol and substance use disorders and associated variables in patients admitted to a drug abuse treatment facility. This was a comparative cross-sectional study involving all patients admitted into Drug Abuse Treatment, Education, and Research (DATER), Unit of the Neuropsychiatric Hospital, Aro, Nigeria within the study period. All subjects had a structured psychiatric interview, a physical examination, laboratory investigations and DATER Questionnaire protocols that elicited socio-demographic, drug and family variables. The patients in 2002 to 2007 versus those of 1992 to 1997 were younger (chi squared 13.29; p,0.01). More last borns were using drugs by 2002 to 2007 (chi squared, 11.37; p,0.01). Cannabis was the most abused drug in 2002 to 2007 (53.5%) as compared to cocaine (44%) in 1992 to 1997 (chi squared 35.5; p,0.001). Polydrug abuse was high in the two periods but significantly the drug combination changed to cannabis in combination with alcohol in 2002 to 2007 as against cocaine in combination with opiates in 1992 to 1997 chi squared 45.3, p 0.001). More patients had co-morbid psychiatric disorders in 2000 to 2007 (67.6% as against 38.5% in 1992 to 1999 chi squared 28.32, p,0.001). In both periods, co-morbidity associated with cannabis use rather than any other drug of abuse as the odds ratio was greater than one. The findings in the trend in the two five year periods underscore the imperatives of continuous evaluation of the drug abuse patient population in treatment which may help drive changes in treatment inputs.
The definition of schizophrenia is currently being extended to include a "prepsychotic" phase. Prepsychosis detection and intervention programs have already been established in Australia. These are intended to identify people "at-risk" for schizophrenia and treat them to prevent their transition into psychosis. However, analysis of leading research in this field shows high levels of arbitrariness in the selection of diagnostic indicators and a lack of convincing evidence about the efficacy of treatments. The favored prophylactic treatment is atypical neuroleptic medication, and sponsorship of research is providing manufacturers of these drugs with a ubiquitous presence in the field. Many risks are associated with atypical neuroleptics and adverse reactions include psychosis. Taken together these factors suggest that prepsychotic intervention may be more concerned with expanding the market for atypical neuroleptics than with preventing schizophrenia.
Affaitati, Giannapia; Martelletti, Paolo; Lopopolo, Mariangela; Tana, Claudio; Massimini, Francesca; Cipollone, Francesco; Lapenna, Domenico; Giamberardino, Maria Adele; Costantini, Raffaele
Primary headaches have high epidemiologic impact but their symptomatic treatment often remains problematic. Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used, but their modality of employment and efficacy/differential efficacy are highly variable. This study investigated current NSAID use for episodic headache at an Italian headache center (January 2000 to February 2013). A retrospective evaluation was performed on 6,443 patient records: migraine (n = 2,330), tension-type headache (TTH; n = 807), and migraine plus TTH (n = 3,306). Among migraine patients, 80% had used NSAIDs in the past year. Preferences were: nimesulide (57%), ketoprofen (25%), and ibuprofen (24%); complete efficacy was significantly higher than incomplete/absent efficacy (P headache was higher than could be hypothesized based on guidelines, with NSAID preferences not entirely coinciding with international recommendations. This outcome suggests the need for greater awareness of all treatment options in headache by both patients and physicians. © 2016 World Institute of Pain.
Emre, Murat; Bernabei, Roberto; Blesa, Rafael; Bullock, Roger; Cunha, Luis; Daniëls, Hugo; Dziadulewicz, Edward; Förstl, Hans; Frölich, Lutz; Gabryelewicz, Tomasz; Levin, Oleg; Lindesay, James; Martínez-Lage, Pablo; Monsch, Andreas; Tsolaki, Magda; van Laar, Teus
Cholinesterase inhibitors constitute one of the mainstays of treatment of Alzheimer disease (AD). Gastrointestinal side effects, difficulty accessing therapeutic doses and poor patient compliance have been identified as barriers to effective treatment with these substances. The rivastigmine transdermal patch provides continuous delivery of drug through the skin into the bloodstream, avoiding the fluctuations in plasma concentration associated with oral administration. This pharmacokinetic profile is associated with reduced side effects, resulting in easier access to expected target doses. These benefits, along with other practical advantages of the transdermal patch, may contribute to enhanced patient compliance. Here, we present a review of the current literature on rivastigmine patch, and offer advice based on our own collective clinical experience. Rivastigmine patch provides an efficient option for managing patients with AD, to be considered among the first line therapies for the disease.
Mozaffari, Shilan; Didari, Tina; Nikfar, Shekoufeh; Abdollahi, Mohammad
Chronic constipation (CC) is a common gastrointestinal (GI) motility disorder that significantly impairs the quality of life in affected subjects. As almost half of the patients suffering from CC are not satisfied with currently available medicines, there is a need to develop new molecules with better effectiveness and tolerability. The authors include all experimental and clinical trials (up to Phase II) about new investigational drugs for the treatment of CC. The article identifies nine new agents: mitemcinal, TD-8954, YKP10811, itopride, RM-131, KWA-0711, elobixibat, velusetrag, and naronapride. All nine agents have shown prokinetic effects in different stages of the development. The mechanisms of new developing drugs include: the activation of 5-hydroxytryptamine type-4 (5-HT4), ghrelin and motilin receptors, antagonizing dopamine type-2 (D2) receptors, inhibition of ileal bile acid reabsorption and acetylcholine esterase, as well as water absorption from the GI tract. At this current point in time, new generations of 5-HT4 receptor agonists (velusetrag, noranopride and YKP10811) are hoped to progress, further in the future, due to better efficiency and safety. However, it is not possible to make a concise conclusion at this current time due to a lack of evidence. Further clinical trials with a longer duration and a larger sample size are warranted.
transport vehicles for effective delivery of two different cancer drugs. In particular, we aim to use two breast cancer drugs, which enhance each...shell structures,26, 27 and dendrimers .28, 29 To date, very few of these strategies have led to particles with distinct release profiles of multiple
Full Text Available Cervical cancer is a highly prevalent cancer that affects women around the world. With the availability of new technologies, researchers have increased their efforts to develop new drug delivery systems in cervical cancer chemotherapy. In this review, we summarized some of the recent research in systematic and localized drug delivery systems and compared the advantages and disadvantages of these methods.
Full Text Available Mechanism-based pharmacokinetic-pharmacodynamic (PK/PD modelling is the standard computational technique for simulating drug treatment of infectious diseases with the potential to enhance our understanding of drug treatment outcomes, drug deployment strategies, and dosing regimens. Standard methodologies assume only a single drug is used, it acts only in its unconverted form, and that oral drugs are instantaneously absorbed across the gut wall to their site of action. For drugs with short half-lives, this absorption period accounts for a significant period of their time in the body. Treatment of infectious diseases often uses combination therapies, so we refined and substantially extended the PK/PD methodologies to incorporate (i time lags and drug concentration profiles resulting from absorption across the gut wall and, if required, conversion to another active form; (ii multiple drugs within a treatment combination; (iii differing modes of action of drugs in the combination: additive, synergistic, antagonistic; (iv drugs converted to an active metabolite with a similar mode of action. This methodology was applied to a case study of two first-line malaria treatments based on artemisinin combination therapies (ACTs, artemether-lumefantrine and artesunate-mefloquine where the likelihood of increased artemisinin tolerance/resistance has led to speculation on their continued long-term effectiveness. We note previous estimates of artemisinin kill rate were underestimated by a factor of seven, both the unconverted and converted form of the artemisinins kill parasites and the extended PK/PD methodology produced results consistent with field observations. The simulations predict that a potentially rapid decline in ACT effectiveness is likely to occur as artemisinin resistance spreads, emphasising the importance of containing the spread of artemisinin resistance before it results in widespread drug failure. We found that PK/PD data is generally very
Andersen, Vibeke; Hansen, Axel Kornerup; Heitmann, Berit Lilienthal
We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such invest...... inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in prospective observational, animal and interventional studies are warranted.......We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies......% CI: 1.73-4.31, p impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic...
Jean Lud eCadet
Full Text Available Heavy use of drugs impacts of the daily activities of individuals in these activities. Several groups of investigators have indeed documented changes in cognitive performance by individuals who have a long history of chronic drug use. In the case of marijuana, a wealth of information suggests that heavy long-term use of the drug may have neurobehavioral consequences in some individuals. In humans, heavy cocaine use is accompanied by neuropathological changes that might serve as substrates for cognitive dysfunctions. Similarly, methamphetamine users suffer from cognitive abnormalities that may be consequent to alterations in structures and functions. Here, we detail the evidence for these neuropsychological consequences. The review suggests that improving the care of our patients will necessarily depend on the better characterization of drug-induced cognitive phenotypes because they might inform the development of better pharmacological and behavioral interventions, with the goal of improving cognitive functions in these subsets of drug users.
Milton, Amy Louise
Addiction is a complex disorder, and one characterised by the acquisition of maladaptive instrumental (drug-seeking and drug-taking) and pavlovian (cue-drug associations) memories. These memories markedly contribute to the long-term risk of relapse, so reduction of the impact of these memories on behaviour could potentially be an important addition to current therapies for addiction. Memory reconsolidation may provide such a target for disrupting well-consolidated pavlovian cue-drug memories ...
Zou, Zhiling; Song, Hongwen; Zhang, Yuting; Zhang, Xiaochu
Drug addiction is a complex neurological dysfunction induced by recurring drug intoxication. Strategies to prevent and treat drug addiction constitute a topic of research interest. Early-stage romantic love is characterized by some characteristics of addiction, which gradually disappear as the love relationship progresses. Therefore, comparison of the concordance and discordance between romantic love and drug addiction may elucidate potential treatments for addiction. This focused review uses...
Zhiling Zou; Hongwen Song; Hongwen Song; Yuting Zhang; Xiaochu Zhang; Xiaochu Zhang; Xiaochu Zhang; Xiaochu Zhang
Drug addiction is a complex neurological dysfunction induced by recurring drug intoxication. Strategies to prevent and treat drug addiction constitute a topic of research interest. Early-stage romantic love is characterized by some characteristics of addiction, which gradually disappear as the love relationship progresses. Therefore, comparison of the concordance and discordance between romantic love and drug addiction may elucidate potential treatments for addiction. This focused review uses...
Burt Associates, Inc., Bethesda, MD.
This report assesses the experiences of clients who had contact with or received drug abuse treatment from programs of the Addiction Services Agency in New York City and the Narcotics Treatment Administration in Washington, D.C. during the early 1970's. To answer the questions of what happens to former clients once they leave drug treatment…
Prendergast, Michael L.; Hall, Elizabeth A.; Wexler, Harry K.
Evaluations of prison-based drug treatment programs typically focus on one or two dichotomous outcome variables related to recidivism. In contrast, this paper uses multiple measures of outcomes related to crime and drug use to examine the impact of prison treatment. Crime variables included self-report data of time to first illegal activity,…
Everitt, Barry J
This review discusses the evidence for the hypothesis that the development of drug addiction can be understood in terms of interactions between Pavlovian and instrumental learning and memory mechanisms in the brain that underlie the seeking and taking of drugs. It is argued that these behaviours initially are goal-directed, but increasingly become elicited as stimulus-response habits by drug-associated conditioned stimuli that are established by Pavlovian conditioning. It is further argued that compulsive drug use emerges as the result of a loss of prefrontal cortical inhibitory control over drug seeking habits. Data are reviewed that indicate these transitions from use to abuse to addiction depend upon shifts from ventral to dorsal striatal control over behaviour, mediated in part by serial connectivity between the striatum and midbrain dopamine systems. Only some individuals lose control over their drug use, and the importance of behavioural impulsivity as a vulnerability trait predicting stimulant abuse and addiction in animals and humans, together with consideration of an emerging neuroendophenotype for addiction are discussed. Finally, the potential for developing treatments for addiction is considered in light of the neuropsychological advances that are reviewed, including the possibility of targeting drug memory reconsolidation and extinction to reduce Pavlovian influences on drug seeking as a means of promoting abstinence and preventing relapse. © 2014 The Author. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Nath, Abhigyan; Kumari, Priyanka; Chaube, Radha
Identification of drug targets and drug target interactions are important steps in the drug-discovery pipeline. Successful computational prediction methods can reduce the cost and time demanded by the experimental methods. Knowledge of putative drug targets and their interactions can be very useful for drug repurposing. Supervised machine learning methods have been very useful in drug target prediction and in prediction of drug target interactions. Here, we describe the details for developing prediction models using supervised learning techniques for human drug target prediction and their interactions.
Vijay, Aishwarya; Bazazi, Alexander R.; Yee, Ilias; Kamarulzaman, Adeeba; Altice, Frederick L.
Background Little is known about attitudes toward and experiences with opioid maintenance therapy (OMT) among people who inject drugs in Malaysia, a country where people who inject drugs comprise 1.3% of the adult population. Methods In 2010, 460 people who inject drugs in Greater Kuala Lumpur, Malaysia were surveyed to evaluate attitudes toward and experience with OMT and treatment readiness. Attitudes towards OMT with both methadone and buprenorphine were assessed using an opinions scale. Multivariable linear regression was used to assess correlates of treatment readiness, measured with the 19-item Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES). Results All 460 participants used opioids and nearly all (99.1%) met criteria for opioid dependence. Few had had previous experience with methadone (9.3%) or buprenorphine (12.6%) maintenance therapy, yet many had used methadone (55.2%) or buprenorphine (51.7%) outside of treatment settings. Fifteen percent had injected buprenorphine in the past month, and of the few that were currently receiving buprenorphine maintenance therapy, almost all were injecting it. The majority of subjects exhibited a moderate level of treatment readiness and a preference for methadone over buprenorphine. Those with low treatment readiness scores were more likely to have previous experience with compulsory drug detention centers (p<0.01), needle/syringe exchange programs (p<0.005), or be of Indian ethnicity (p<0.001). Past use of methadone (p<0.01), older age (p<0.001), stress symptom severity (p<0.001), and sharing of needles or syringes (p<0.05) were associated with higher treatment readiness scores. Conclusion There are suboptimal levels of OMT experience among people who inject drugs that may be improved by addressing factors that influence patient attitudes. Those individuals with moderate treatment readiness may be targeted by brief motivational and cognitive interventions in primary care, prisons or OMT clinics
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.
Metsch, Lisa; Philbin, Morgan M; Parish, Carrigan; Shiu, Karen; Frimpong, Jemima A; Giang, Le Minh
The article reviews data on HIV testing, treatment, and care outcomes for women who use drugs in 5 countries across 5 continents. We chose countries in which the HIV epidemic has, either currently or historically, been fueled by injection and non-injection drug use and that have considerable variation in social structural and drug policies: Argentina, Vietnam, Australia, Ukraine, and the United States. There is a dearth of available HIV care continuum outcome data [ie, testing, linkage, retention, antiretroviral therapy (ART) provision, viral suppression] among women drug users, particularly among noninjectors. Although some progress has been made in increasing HIV testing in this population, HIV-positive women drug users in 4 of the 5 countries have not fully benefitted from ART nor are they regularly engaged in HIV care. Issues such as the criminalization of drug users, HIV-specific criminal laws, and the lack of integration between substance use treatment and HIV primary care play a major role. Strategies that effectively address the pervasive factors that prevent women drug users from engaging in HIV care and benefitting from ART and other prevention services are critical. Future success in enhancing the HIV continuum for women drug users should consider structural and contextual level barriers and promote social, economic, and legal policies that overhaul the many years of discrimination and stigmatization faced by women drug users worldwide. Such efforts must emphasis the translation of policies into practice and approaches to implementation that can help HIV-infected women who use drugs engage at all points of the HIV care continuum.
Iser, David M; Sasadeusz, Joseph J
Coinfection with HIV and hepatitis B virus (HBV) has become a significant global health problem. Liver disease is now one of the leading causes of morbidity and mortality in individuals with HIV, particularly those with viral hepatitis. There are a number of agents available with dual activity against HIV and HBV, and effective treatment depends on understanding the potential advantages and pitfalls in using these agents. There are a number of unresolved issues in the management of HIV/HBV coinfection. These include the role of liver biopsy, the significance of normal aminotransferase levels, serum HBV DNA threshold for treatment, treatment end-points, and the treatment of HBV when HIV does not yet require treatment. Treatment of HBV should be considered in individuals with HIV/HBV coinfection with evidence of significant fibrosis (>/=F2), or with elevated serum HBV DNA levels (>2000 IU/mL). Sustained suppression of serum HBV DNA to below the level of detection by the most sensitive available assay should be the goal of therapy, and, at present, treatment of HBV in HIV/HBV coinfection is lifelong. If antiretroviral therapy is required, then two agents with anti-HBV activity should be incorporated into the regimen. If antiretroviral therapy is not required, then the options are pegylated interferon, adefovir or the early introduction of antiretroviral therapy. Close monitoring is necessary to detect treatment failure or hepatic flares, such as immune reconstitution disease. Further studies of newer anti-HBV agents in individuals HIV/HBV coinfection may advance treatment of this important condition.
Castro, Carlos; Cardona, Andres Felipe; Reveiz, Ludovic; Serrano, Silvia Juliana; Carranza, Hernan; Vargas, Carlos Alberto; Reguart, Noemi; Campo, Felipe; Ospina, Edgar Guillermo; Sanchez, Oswaldo; Torres, Diana; Otero, Jorge Miguel
to perform a review of evidence about the treatment of non-small cell lung cancer (NSCLC). Source of data: the information was obtained from searches conducted in Medline, CCTR, Biosis, Embase, Lilacs and CINHAL. We also collected the most representative references presented during the last five years at Asco, ESMO and IASLC. Data extraction: data were extracted by associate members to the ONCOL Group. The collection of information did not follow a uniform strategy. Results of data synthesis: therapy for NSCLC can prolong survival and improve quality of life, but the majority of advanced stage patients dies due to disease progression within 2 years, meaning that there is room for improvement. The standard chemotherapy for NSCLC involves one of a number of platinum-based doublets that have been shown to improve survival when compared with single agents or best supportive care. These doublets are generally comparable in terms of efficacy, differing primarily in their toxicity profiles. However, encouraging new options may be approaching, including therapies targeted to specific patient subpopulations, and the use of combinations of current and new drugs to produce synergistic effects. This review present a detailed analysis of current evidence regarding the treatment of NSCLC based on a representative case series. This review didn't conduct a systematic evaluation of the evidence. Conclusion: medical therapy for NSCLC produces positive changes in main outcomes, including quality of life
Martin, Roland; Sospedra, Mireia; Rosito, Maria; Engelhardt, Britta
Multiple sclerosis (MS) is the most common inflammatory disorder of the central nervous system (CNS) in young adults. When MS is not treated, it leads to irreversible and severe disability. The etiology of MS and its pathogenesis are not fully understood. The recent discovery that MS-associated genetic variants code for molecules related to the function of specific immune cell subsets is consistent with the concept of MS as a prototypic, T-cell-mediated autoimmune disease targeting the CNS. While the therapeutic efficacy of the currently available immunomodulatory therapies further strengthen this concept, differences observed in responses to MS treatment as well as additional clinical and imaging observations have also shown that the autoimmune pathogenesis underlying MS is much more complex than previously thought. There is therefore an unmet need for continued detailed phenotypic and functional analysis of disease-relevant adaptive immune cells and tissues directly derived from MS patients to unravel the immune etiology of MS in its entire complexity. In this review, we will discuss the currently available MS treatment options and approved drugs, including how they have contributed to the understanding of the immune pathology of this autoimmune disease. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Cash, W J
Hepatic encephalopathy (HE) is defined as a metabolically induced, potentially reversible, functional disturbance of the brain that may occur in acute or chronic liver disease. Standardized nomenclature has been proposed but a standardized approach to the treatment, particularly of persistent, episodic and recurrent encephalopathy associated with liver cirrhosis has not been proposed. This review focuses on the pathogenesis and treatment of HE in patients with cirrhosis. The pathogenesis and treatment of hepatic encephalopathy in fulminant hepatic failure is quite different and is reviewed elsewhere.
Pleyer, U; Pohlmann, D; Stübiger, N
Treatment of autoimmune diseases has undergone significant changes and developments in recent years. New classes of active substances, in particular biologics and small molecules have resulted in previously unknown success in the treatment of many diseases. In particular patients suffering from autoimmune rheumatic or dermatological diseases have benefited. For autoimmune uveitis there are numerous reports indicating excellent therapeutic and preventive effects; however, statutory approval for therapy in adults is still pending. This article outlines recent advances and future therapeutic options for the treatment of posterior segment noninfectious uveitis.
Tarpada, Sandip P; Morris, Matthew T; Lian, Jayson; Rashidi, Sina
Despite advances elucidating the causes of lateral and medial epicondylitis, the standard of care remains conservative management with NSAIDs, physical therapy, bracing, and rest. Scar tissue formation provoked by conservative management creates a tendon lacking the biomechanical properties and mechanical strength of normal tendon. The following review analyzes novel therapies to regenerate tendon and regain function in patients with epicondylitis. These treatments include PRP injection, BMAC, collagen-producing cell injection, and stem cell treatments. While these treatments are in early stages of investigation, they may warrant further consideration based on prospects of pain alleviation, function enhancement, and improved healing.
Becker, D.V.; Hurley, J.R.
Radioiodine appears to be increasingly selected as the primary form of therapy for most hyperthyroid adults. Some controversy exists concerning the use of I-131 in children and adolescents as well as in some patients with toxic nodular goiter. The technical aspects of radioiodine administration reviewed in this chapter include the biologic basis of I-131 use, dose strategies, measurement and evaluation of radioiodine parameters, and I-125 treatment of hyperthyroidism. The management of patients before and after I-131 treatment is discussed as well as posttreatment hypothyroidism and complications of radioiodine treatment
Yonucu, Sirin; Yιlmaz, Defne; Phipps, Colin; Unlu, Mehmet Burcin; Kohandel, Mohammad
Tumor-induced angiogenesis leads to the development of leaky tumor vessels devoid of structural and morphological integrity. Due to angiogenesis, elevated interstitial fluid pressure (IFP) and low blood perfusion emerge as common properties of the tumor microenvironment that act as barriers for drug delivery. In order to overcome these barriers, normalization of vasculature is considered to be a viable option. However, insight is needed into the phenomenon of normalization and in which conditions it can realize its promise. In order to explore the effect of microenvironmental conditions and drug scheduling on normalization benefit, we build a mathematical model that incorporates tumor growth, angiogenesis and IFP. We administer various theoretical combinations of antiangiogenic agents and cytotoxic nanoparticles through heterogeneous vasculature that displays a similar morphology to tumor vasculature. We observe differences in drug extravasation that depend on the scheduling of combined therapy; for concurrent therapy, total drug extravasation is increased but in adjuvant therapy, drugs can penetrate into deeper regions of tumor.
Wiersinga, W. Joost
Sepsis continues to be a leading cause of ICU death. This review summarizes current knowledge on sepsis pathogenesis and new therapeutical strategies. Although systemic inflammatory response syndrome predominates in early sepsis, the compensatory anti-inflammatory response syndrome causes
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G V Lukina
Full Text Available Summary Aljlutup is an effective and well tolerable drug which not only decreases pains and other clinical manifestations of secondary synovitis but also has positive effect on the structure of articular cartilage.
Salido-Vallejo, R; Garnacho-Saucedo, G; Moreno-Giménez, J C
Facial angiofibromas are hamartomatous growths that are closely associated with tuberous sclerosis complex and, in fact, they constitute one of the main diagnostic criteria for that disease. These lesions composed of blood vessels and fibrous tissue appear on the face at an early age. Since they have important physical and psychological repercussions for patients, several treatment options have been used to remove them or improve their appearance. However, the lack of treatment guidelines prevents us from developing a common protocol for patients with this condition. The present article aims to review the treatments for facial angiofibromas used to date and to propose a new evidence-based treatment protocol. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.
Full Text Available Koh Takeuchi,1 Atsushi Hirota,2 Sachito Minegishi,1 Jotaro Kobayashi,1 Keiji Tsuchiya3 1Division of Cardiovascular Surgery, 2Department of Neonatology, 3Department of Pediatrics, Japanese Red Cross Medical Center, Shibuya, Tokyo, Japan Abstract: Pharmacological and/or surgical closure of a hemodynamically significant patent ductus arteriosus (PDA in the very premature infant has been the standard of care over the past few decades. However, the rationale for closure of PDA has recently been challenged. In this article, three ways of approaching the closure of PDA including pharmacological treatment, catheter intervention, and surgical intervention, are reviewed in detail. In addition, the different treatment strategies applied in clinical care are evaluated with a focus on the discussion of the available evidence of PDA treatment in the literature. Keywords: patent ductus arteriosus, premature infant, treatment option
Full Text Available Wai Tong Chien, Annie LK Yip School of Nursing, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Abstract: During the last three decades, an increasing understanding of the etiology, psychopathology, and clinical manifestations of schizophrenia spectrum disorders, in addition to the introduction of second-generation antipsychotics, has optimized the potential for recovery from the illness. Continued development of various models of psychosocial intervention promotes the goal of schizophrenia treatment from one of symptom control and social adaptation to an optimal restoration of functioning and/or recovery. However, it is still questionable whether these new treatment approaches can address the patients' needs for treatment and services and contribute to better patient outcomes. This article provides an overview of different treatment approaches currently used in schizophrenia spectrum disorders to address complex health problems and a wide range of abnormalities and impairments resulting from the illness. There are different treatment strategies and targets for patients at different stages of the illness, ranging from prophylactic antipsychotics and cognitive–behavioral therapy in the premorbid stage to various psychosocial interventions in addition to antipsychotics for relapse prevention and rehabilitation in the later stages of the illness. The use of antipsychotics alone as the main treatment modality may be limited not only in being unable to tackle the frequently occurring negative symptoms and cognitive impairments but also in producing a wide variety of adverse effects to the body or organ functioning. Because of varied pharmacokinetics and treatment responsiveness across agents, the medication regimen should be determined on an individual basis to ensure an optimal effect in its long-term use. This review also highlights that the recent practice guidelines and standards have
Machado, Joana; Almeida, Paulo; Fernandes, Sampaio; Marques, Arcelina; Vaz, Mário
An advanced stage of a tooth decay promotes an extremely damaged tooth that needs endodontic treatment to be restored. When satisfactory coronal tooth structure remains, an artificial crown can be placed without a post. On the other hand, the treatment