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Sample records for future treatment strategies

  1. Strategies of temozolomide in future glioblastoma treatment

    PubMed Central

    Lee, Chooi Yeng

    2017-01-01

    Glioblastoma multiforme (GBM) may be one of the most challenging brain tumors to treat, as patients generally do not live more than 2 years. This review aimed to give a timely review of potential future treatments for GBM by looking at the latest strategies, involving mainly the use of temozolomide (TMZ). Although these studies were carried out either in vitro or in rodents, the findings collectively suggested that we are moving toward developing a more efficacious therapy for GBM patients. Nanoparticles preparation was, by far, the most extensively studied strategy for targeted brain delivery. Therefore, the first section of this review presents a treatment strategy using TMZ-loaded nanocarriers, which encompassed nanoparticles, nanoliposomes, and nanosponges. Besides nanocarriers, new complexes that were formed between TMZ and another chemical agent or molecule have shown increased cytotoxicity and antitumor activity. Another approach was by reducing GBM cell resistance to TMZ, and this was achieved either through the suppression of metabolic change occurring in the cells, inhibition of the DNA repair protein, or up-regulation of the protein that mediates autophagy. Finally, the review collates a list of substances that have demonstrated the ability to suppress tumor cell growth. PMID:28123308

  2. Ulcerative colitis: current and future treatment strategies.

    PubMed

    Lissner, Donata; Siegmund, Britta

    2013-01-01

    Since the incidence of inflammatory bowel diseases including ulcerative colitis is continuously increasing worldwide, there is a strong need for effective treatment strategies. However, there is no therapy allowing for healing ulcerative colitis; consequently, the available medications will have to be applied at their best. The preferred option for mild pan- or left-sided colitis is still mesalazine. One can only emphasize that the formulations allowing for once daily dosing are not only equally effective, but even facilitate the implication of long-term therapy in daily life. In case steroids are frequently required to control disease, further immunosuppressive therapy should be introduced in order to minimize steroid exposure. Thiopurines represent the first-choice immunosuppressive medication. In more severe cases, early escalation to combinatory therapies with anti-TNF antibodies should be considered with the possibility of therapy deescalation after induction of remission. Major difficulties arise with steroid-refractory acute flares. Here cyclosporine as well as anti-TNF strategies can be initiated. However, in case of severe disease, the high 1-year colectomy rate of about 50% should be considered. If short-term surgery is an option due to disease severity, cyclosporine might be advantageous since the half-life is short compared to infliximab or adalimumab. The central problem of all therapeutic approaches is that because we chase after the disease, solid markers that allow for prediction of the future disease course are desirable. In fact, the CD8+ transcriptome might fill this gap and will potentially lead to the classification of patients in low- and high-risk groups. Copyright © 2013 S. Karger AG, Basel.

  3. Anthelmintic treatment strategies: current status and future.

    PubMed

    Williams, J C

    1997-11-01

    Despite the array of anthelmintics and endectocides and delivery systems available for use in the prevention and control of nematode parasites of ruminants, the number of highly effective control programs that have been developed and even the number of such programs that have been successfully implemented in commercial animal production, there have been no recent innovations or discoveries in regard to strategies, new anthelmintics, or systems for controlling nematode parasites through anthelmintic use. In the traditional sense of chemotherapy-chemoprophylaxis, we have probably achieved the maximum effect of what is possible from excellent anthelmintics developed by the pharmaceutical industry over the last 35 years, i.e. from thiabendazole through levamisole and morantel tartrate, to more advanced benzimidazoles and to the avermectins and milbemycins. At the core of all anthelmintic treatment-related problems is the lingering conception among a large body of animal producers that anthelmintic treatment is the only effort needed to control parasitism and its effects on host animals. This concept has given rise to the long-standing difficulty of drug resistance in sheep nematodes and the not remote possibility of its development in nematodes of cattle. Along with this are serious concerns over environmental toxicity, tissue residues and enormous financial investment to develop new and novel anthelmintic compounds. Progress is being made in current and intensive searches for development and testing of control approaches alternative to anthelmintics, e.g. helminth vaccines, biological control agents such as fungi, selection of resistant sires, alternative chemicals and nematode growth regulators. A timetable for when alternative controls can be developed fully and put into practical use cannot be predicted. It is universally acknowledged among parasitologists that existing anthelmintics must be preserved and utilized judiciously to ensure continued effectiveness. A

  4. Burn wound healing: present concepts, treatment strategies and future directions.

    PubMed

    Oryan, A; Alemzadeh, E; Moshiri, A

    2017-01-02

    Burns are the most extensive forms of soft tissue injuries occasionally resulting in extensive and deep wounds and death. Burns can lead to severe mental and emotional distress, because of excessive scarring and skin contractures. Treatment of burns has always been a difficult medical problem and many different methods have been used to treat such injuries, locally. Biofilms are a collection of microorganisms that delay wound healing. One of the new methods of prevention and treatment of burn wound infections is application of antimicrobials, which act on biofilms and prevent the wound infection. Biofilm initiates a persistent, low-grade, inflammatory response, impairing both the epithelialisation and granulation tissue formation. Skin grafts have been shown to dramatically reduce deaths from infection. However, grafting has considerable limitations. Such injuries are long-lasting and many patients suffer from chronic pain for a long time. Tissue engineering is a new approach in reducing the limitations of conventional treatments and producing a supply of immunologically tolerant artificial tissue, leading to a permanent solution for damaged tissues; such criteria make it a cost-effective and reliable treatment modality. To overcome the present limitations of burn wound healing, knowledge about the latest findings regarding healing mechanisms is important. Here the authors discuss the most important events regarding burn wound healing and review the latest treatment strategies that have been used for burn wounds from in vitro to clinical levels. Finally, we discuss the role of tissue engineering and regenerative medicine in the future of burn wound healing, modelling and remodelling.

  5. Treatment strategies for inherited optic neuropathies: past, present and future.

    PubMed

    Yu-Wai-Man, P; Votruba, M; Moore, A T; Chinnery, P F

    2014-05-01

    Bilateral visual loss secondary to inherited optic neuropathies is an important cause of registrable blindness among children and young adults. The two prototypal disorders seen in clinical practice are Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA). About 90% of LHON cases are due to one of three mitochondrial DNA (mtDNA) point mutations: m.3460G>A, m.11778G>A, and m.14484T>C, which affect critical complex I subunits of the mitochondrial respiratory chain. The majority of patients with DOA harbour pathogenic mutations within OPA1, a nuclear gene that codes for a multifunctional inner mitochondrial membrane protein. Despite their contrasting genetic basis, LHON and DOA share overlapping pathological and clinical features that serve to highlight the striking tissue-specific vulnerability of the retinal ganglion cell (RGC) layer to disturbed mitochondrial function. In addition to severe visual loss secondary to progressive optic nerve degeneration, a subgroup of patients will also develop a more aggressive syndromic phenotype marked by significant neurological deficits. The management of LHON and DOA remains largely supportive, but major advances in our understanding of the mechanisms underpinning RGC loss in these two disorders are paving the way for novel forms of treatment aimed at halting or reversing visual deterioration at different stages of the disease process. In addition to neuroprotective strategies for rescuing RGCs from irreversible cell death, innovative in vitro fertilisation techniques are providing the tantalising prospect of preventing the germline transmission of pathogenic mtDNA mutations, eradicating in so doing the risk of disease in future generations.

  6. Pharmacological treatment for Alzheimer's disease: current approaches and future strategies.

    PubMed

    Fan, Ling-Yun; Chiu, Ming-Jang

    2010-12-01

    More than a decade after the first approval of the use of acetylcholine esterase inhibitor on patients with Alzheimer's disease, we still not have a single treatment or combination therapy that can effectively stop or reverse the relentless progression of such neurodegenerative disease. Recently therapeutics targeting amyloid hypothesis have undergone scrutiny by many clinical trials. These include gamma secretase inhibitor for reducing beta amyloid formation, agents for preventing aggregation of amyloid oligomers, and immunotherapy for enhancing clearance of amyloid and plaque. Therapies targeting hyperphosphorylated tau is another promising mechanism to be tackled with. Other agents enforcing mitochondria functions, enhancing serotonin receptors, modulating advanced glycation end products, and neurotrophic factors, as well as other therapies are also emerging. We review current treatments and therapeutic strategies already undergone different stage of clinical trails in this report. We propose that therapeutics of various combination composed of symptomatic treatments and disease modifying therapies will become standard regimens of AD treatment with much better efficacy than current approaches.

  7. Ulcerative Colitis: Current Treatment Strategies and Future Prospects

    PubMed Central

    Peppercorn, Mark A.

    2009-01-01

    Ulcerative colitis (UC) is a disease of unknown etiology characterized by inflammation of the mucosa and occasionally the submucosa of the colon. Conventional drug therapy for UC involves use of aminosalicylates, corticosteroids, azathioprine/6-mercaptopurine, cyclosporine and anti-tumor necrosis factor therapy. Alternative therapies include probiotics, nicotine and fish oil. Drugs like tacrolimus, rosiglitazone and Trichuris suis ova are being evaluated for use in UC patients. With the new biologic agents, new treatment options for UC continue to evolve. In this article we will discuss the conventional drugs, the alternative therapies and the management strategies according to the severity and extent of UC. PMID:21180538

  8. Ulcerative colitis: current treatment strategies and future prospects.

    PubMed

    Garud, Sagar; Peppercorn, Mark A

    2009-03-01

    Ulcerative colitis (UC) is a disease of unknown etiology characterized by inflammation of the mucosa and occasionally the submucosa of the colon. Conventional drug therapy for UC involves use of aminosalicylates, corticosteroids, azathioprine/6-mercaptopurine, cyclosporine and anti-tumor necrosis factor therapy. Alternative therapies include probiotics, nicotine and fish oil. Drugs like tacrolimus, rosiglitazone and Trichuris suis ova are being evaluated for use in UC patients. With the new biologic agents, new treatment options for UC continue to evolve. In this article we will discuss the conventional drugs, the alternative therapies and the management strategies according to the severity and extent of UC.

  9. Development of early treatment strategies for high-risk myeloma precursor disease in the future.

    PubMed

    Landgren, Ola; Rajkumar, S Vincent

    2011-01-01

    Smoldering myeloma (SMM) is a precursor state of multiple myeloma. It is defined by an M-protein concentration ≥3 g/dL and/or ≥10% clonal bone marrow plasma cells, in the absence of end-organ damage. Based on clinical observations, the natural history of SMM varies greatly, from stable, monoclonal gammopathy of undetermined significance (MGUS)-like disease to highly progressive disease. Using conventional clinical markers, SMM patients can be stratified into clinical risk groups. However, due to considerable molecular heterogeneity, we currently lack reliable markers to predict prognosis for individual SMM patients. Based on the International Myeloma Working Group 2010 guidelines, patients diagnosed with MGUS and SMM should not be treated outside of clinical trials. Overall, treatment trials for MGUS patients are complicated, as these individuals are relatively healthy and the majority has a low life-time risk of progression, especially when other causes of death are taken into account. In contrast to MGUS, early treatment strategies for SMM are particularly attractive, as the rate of progression to multiple myeloma is substantially higher. Until recently, potent drugs with reasonable toxicity profiles have not been available for the development of early multiple myeloma treatment strategies. This review discusses how the integration of novel biological markers and clinical monitoring of SMM could facilitate the development of early treatment strategies for high-risk SMM patients in the future. Copyright © 2011. Published by Elsevier Inc.

  10. Demystifying Immunotherapy in Prostate Cancer: Understanding Current and Future Treatment Strategies

    PubMed Central

    Madan, Ravi A.; Gulley, James L.; Kantoff, Philip W.

    2013-01-01

    Immunotherapy has emerged as a viable therapeutic option for patients with prostate cancer. There are multiple potential strategies that employ the immune system including therapeutic cancer vaccines that are designed to stimulate immune cells to target antigens expressed by cancer cells. Sipuleucel-T is a vaccine currently approved for the treatment of minimally symptomatic metastatic prostate cancer, while the vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab are in phase III testing. Although there are no short term changes in disease progression or available biomarkers to assess response, these agents appear to improve survival. One hypothesis suggests that this apparent paradox can be explained by the growth moderating effects of these treatments which do not cause tumor size to diminish, but rather stall or slow their growth rate over time. For this reason the use of immunotherapy earlier in the disease process is being investigated. Another approach is to block immune regulatory mechanisms mediated by the molecules CTLA-4 and PD-1. Additional future strategies will combine immunotherapy with other standard therapies, potentially enhancing the latter’s clinical impact and thereby improving both time to progression and overall survival due to the combined effects of both treatments. Prospective trials are currently evaluating these hypotheses and will ultimately serve to optimize immunotherapy in the treatment of prostate cancer. PMID:23337757

  11. Current and Future Pharmacological Treatment Strategies in X-Linked Adrenoleukodystrophy

    PubMed Central

    Berger, Johannes; Pujol, Aurora; Aubourg, Patrick; Forss-Petter, Sonja

    2010-01-01

    Mutations in the ABCD1 gene cause the clinical spectrum of the neurometabolic disorder X-linked adrenoleukodystrophy/adrenomyeloneuropathy (X-ALD/AMN). Currently, the most efficient therapeutic opportunity for patients with the cerebral form of X-ALD is hematopoietic stem cell transplantation and possibly gene therapy of autologous hematopoietic stem cells. Both treatments, however, are only accessible to a subset of X-ALD patients, mainly because of the lack of markers that can predict the onset of cerebral demyelination. Moreover, for female or male X-ALD patients with AMN, currently only unsatisfying therapeutic opportunities are available. Thus, this review focuses on current and urgently needed future pharmacological therapies. The treatment of adrenal and gonadal insufficiency is well established, whereas applications of immunomodulatory and immunosuppressive drugs have failed to prevent progression of cerebral neuroinflammation. The use of Lorenzo's oil and the inefficacy of lovastatin to normalize very-long-chain fatty acids in clinical trials as well as currently experimental and therefore possible future therapeutic strategies are reviewed. The latter include pharmacological gene therapy mediated by targeted upregulation of ABCD2, the closest homolog of ABCD1, antioxidative drug treatment, small molecule histone deacetylase inhibitors such as butyrates and valproic acid, and other neuroprotective attempts. PMID:20626746

  12. Immunological Aspect of Radiation-Induced Pneumonitis, Current Treatment Strategies, and Future Prospects

    PubMed Central

    Kainthola, Anup; Haritwal, Teena; Tiwari, Mrinialini; Gupta, Noopur; Parvez, Suhel; Tiwari, Manisha; Prakash, Hrideysh; Agrawala, Paban K.

    2017-01-01

    Delivery of high doses of radiation to thoracic region, particularly with non-small cell lung cancer patients, becomes difficult due to subsequent complications arising in the lungs of the patient. Radiation-induced pneumonitis is an early event evident in most radiation exposed patients observed within 2–4 months of treatment and leading to fibrosis later. Several cytokines and inflammatory molecules interplay in the vicinity of the tissue developing radiation injury leading to pneumonitis and fibrosis. While certain cytokines may be exploited as biomarkers, they also appear to be a potent target of intervention at transcriptional level. Initiation and progression of pneumonitis and fibrosis thus are dynamic processes arising after few months to year after irradiation of the lung tissue. Currently, available treatment strategies are challenged by the major dose limiting complications that curtails success of the treatment as well as well being of the patient’s future life. Several approaches have been in practice while many other are still being explored to overcome such complications. The current review gives a brief account of the immunological aspects, existing management practices, and suggests possible futuristic approaches. PMID:28512460

  13. A review of treatment strategies for hydrofluoric acid burns: current status and future prospects.

    PubMed

    Wang, Xingang; Zhang, Yuanhai; Ni, Liangfang; You, Chuangang; Ye, Chunjiang; Jiang, Ruiming; Liu, Liping; Liu, Jia; Han, Chunmao

    2014-12-01

    Hydrofluoric acid (HF), a dangerous inorganic acid, can cause severe corrosive effects and systemic toxicity. HF enters the human body via where it contacts, such as skin and mucosa, alimentary and respiratory tracts, and ocular surfaces. In the recent years, the incidence of HF burn has tended to increase over time. The injury mechanism of HF is associated primarily with the massive absorption of HF and the release of hydrogen ions. Correct diagnosis and timely treatment are especially important for HF burns. The critical procedure to treat HF burn is to prevent on-going HF absorption, and block the progressive destruction caused by fluoride ions. Due to the distinct characteristics of HF burns, the topical treatment, as well as systemic support, has been emphasised. Whereas, management of patients with HF burns remains a great challenge in some situations. To date, there has been no widely accepted protocol for the rescue of HF burns, partly due to the diversity of HF burns. This paper overviews the current status and problems of treatment strategies for HF burns, for the purpose of promoting the future researches and improvement. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

  14. Current and future pharmacological treatment strategies with regard to aortic disease in Marfan syndrome.

    PubMed

    Hartog, Alexander W; Franken, Romy; Zwinderman, Aeilko H; Groenink, Maarten; Mulder, Barbara J M

    2012-04-01

    Marfan syndrome is a multisystemic connective tissue disorder caused mainly by mutations in the fibrillin-1 gene. The entire cardiovascular system is affected in patients with Marfan syndrome. Aortic root dilatation, aortic valve regurgitation or - the most feared and life-threatening symptom - aortic root dissection are the most common manifestations. Therapeutic strategies, such as prophylactic aortic root surgery and pharmacological therapy, focus on the prevention of aortic dissection. Currently, the standard medicinal treatments targeting aortic dilatation and dissection consist of agents generally used to lower blood pressure and/or the inotropic state of the heart. By these means, the cyclic repetitive forces exerted on the aortic wall are diminished and thus the onset of aortic dilatation is potentially prevented. Although these pharmacological agents may offer some benefit in reduction of aortic aneurysm expansion rate, they do not target the underlying cause of the progressive aortic degradation. This review discusses the effectiveness of frequently prescribed medications used to prevent and delay aortic complications in Marfan syndrome. New insights on the biochemical pathways leading to aortic disease are also discussed to highlight new targets for pharmacological therapy. Recent insights in the transforming growth factor beta signaling pathway and inflammatory mechanisms in a well-established mouse model of Marfan syndrome, have led to studies exploring new pharmacological treatment strategies with doxycycline, statins and angiotensin II receptor blockers. Pharmacological therapy is focused more on prevention than on delay of aortic wall pathology in Marfan syndrome. Of the new pharmacological treatment strategies targeting aortic pathology in Marfan syndrome, angiotensin receptor type 1 blockers are promising candidates, with several clinical trials currently ongoing.

  15. Hereditary motor and sensory neuropathies: Understanding molecular pathogenesis could lead to future treatment strategies.

    PubMed

    Jerath, Nivedita U; Shy, Michael E

    2015-04-01

    Inherited peripheral neuropathies, like many other degenerative disorders, have been challenging to treat. At this point, there is little specific therapy for the inherited neuropathies other than genetic counseling as well as symptomatic treatment and rehabilitation. In the past, ascorbic acid, progesterone antagonists, and subcutaneous neurotrophin-3 (NT3) injections have demonstrated improvement in animal models of CMT 1A, the most common inherited neuropathy, but have failed to translate any effect in humans. Given the difficulty in treatment, it is important to understand the molecular pathogenesis of hereditary neuropathies in order to strategize potential future therapies. The hereditary neuropathies are in an era of molecular insight and over the past 20 years, more than 78 subtypes of Charcot Marie Tooth disease (CMT) have been identified and extensively studied to understand the biological pathways in greater detail. Next generation molecular sequencing has also improved the diagnosis as well as the understanding of CMT. A greater understanding of the molecular pathways will help pave the way to future therapeutics of CMT. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Understanding resistance to EGFR inhibitors—impact on future treatment strategies

    PubMed Central

    Wheeler, Deric L.; Dunn, Emily F.; Harari, Paul M.

    2010-01-01

    EGFR is a tyrosine kinase that participates in the regulation of cellular homeostasis. Following ligand binding, EGFR stimulates downstream cell signaling cascades that influence cell proliferation, apoptosis, migration, survival and complex processes, including angiogenesis and tumorigenesis. EGFR has been strongly implicated in the biology of human epithelial malignancies, with therapeutic applications in cancers of the colon, head and neck, lung, and pancreas. Accordingly, targeting EGFR has been intensely pursued, with the development of a series of promising molecular inhibitors for use in clinical oncology. As is common in cancer therapy, challenges with respect to treatment resistance emerge over time. This situation is certainly true of EGFR inhibitor therapies, where intrinsic and acquired resistance is now well recognized. In this Review, we provide a brief overview regarding the biology of EGFR biology, preclinical and clinical development of EGFR inhibitors, and molecular mechanisms that underlie the development of treatment resistance. A greater understanding of the mechanisms that lead to EGFR resistance may provide valuable insights to help design new strategies that will enhance the impact of this promising class of inhibitors for the treatment of cancer. PMID:20551942

  17. The future of therapy for relapsed/refractory multiple myeloma: emerging agents and novel treatment strategies.

    PubMed

    Moreau, Philippe

    2012-07-01

    Treatment of relapsed or refractory multiple myeloma (MM) continues to present a therapeutic challenge. The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, and the proteasome inhibitor (PI) bortezomib, have dramatically improved clinical outcomes for patients with newly diagnosed and relapsed/refractory MM. However, nearly all patients will eventually relapse or become refractory to these drugs. Numerous agents are currently in development for the treatment of relapsed/refractory MM. Those farthest along in clinical development include new IMiDs (pomalidomide), new PIs (eg, carfilzomib, MLN9708, and marizomib), histone deacetylase inhibitors (eg, panobinostat and vorinostat), monoclonal antibodies (eg, elotuzumab, siltuximab, and BT062), and signal transduction modulators (eg, perifosine). These emerging agents with diverse mechanisms of action have demonstrated promising anti-tumor activity in patients with relapsed/refractory MM, and rationally designed combinations with established agents are being investigated in the clinic. These new agents are creating opportunities to target multiple pathways, overcome resistance, and improve clinical outcomes, particularly for those patients who are refractory to approved novel agents. This article describes emerging antimyeloma agents in mid-stage to late-stage clinical development, and highlights the novel treatment approaches and combination strategies being evaluated in the relapsed/refractory setting. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Human prostate cancer vaccines – proposed mechanisms of action and future combinatorial treatment strategies

    PubMed Central

    Geary, Sean M.; Lemke, Caitlin D.; Lubaroff, David M.; Salem, Aliasger K.

    2015-01-01

    Prostate cancer (PCa) is responsible for the deaths of more than 33,000 American men annually. Once PCa has become metastatic there is no curative treatment. Oncologists worldwide are becoming increasingly convinced that alternative therapies to chemotherapy and radical prostatectomy need to be explored. Cancer vaccines (CaVacs) that promote the cancer patient’s own immune system to develop a tumor-specific cytotoxic T lymphocyte-mediated immune attack have been investigated in clinical trials with modest yet encouraging results. Here we look at the rationale behind different prostate CaVacs and propose key immune events that are likely to contribute to the efficacy of each vaccine. Finally, we prognosticate upon what improvements may be required to generate more effective CaVacs in the future with full consideration of the mechanisms of action. PMID:23399727

  19. Treatment strategies for nodal and gastrointestinal follicular lymphoma: Current status and future development

    PubMed Central

    Watanabe, Takuya

    2010-01-01

    In recent years, therapies for follicular lymphoma (FL) have steadily improved. A series of phase III trials comparing the effect of rituximab with chemotherapy vs chemotherapy alone in treating FL have indicated significant improvements in progression-free survival (PFS) and overall survival. Recent studies have found that prolonged response durations and PFS were obtained with maintenance therapy using rituximab or interferon after completion of first line therapy. For patients with relapsed or refractory FL, phase II studies have assessed the effectiveness of combination therapies using a Toll-like receptor-9 agonist (1018ISS), oblimersen sodium (a Bcl-2 antisense oligonucleotide), bendamustine, and rituximab, as well as veltuzumab, a new humanized anti-CD20 antibody, and epratuzumab. In addition, the effectiveness of yttrium-90 ibritumomab tiuxetan and iodine-131 tositumomab as radioimmunotherapies has been reported. Furthermore, three phase III studies on an idiotype vaccine are near completion. Unfortunately, these vaccines, which appeared highly effective in phase I and II trials, do not appear to result in prolonged PFS. This report will summarize the current knowledge on therapies for treatment of FL, and will conclude with a brief discussion of feasible future options for effective treatments. Lastly, we added descriptions of the management of gastrointestinal FL, which is considered to be controversial because it is rare. PMID:21105187

  20. Any Future for Fecal Microbiota Transplantation as Treatment Strategy for Inflammatory Bowel Diseases?

    PubMed

    Kump, Patrizia; Högenauer, Christoph

    Fecal microbiota transplantation (FMT) is a novel therapeutic procedure aiming at restoring a normal intestinal microbiota by application of fecal microorganisms from a healthy subject into the gastrointestinal tract of a patient. FMT is the most effective treatment for recurrent Clostridium difficile infections (CDI). These infections also occur in patients with inflammatory bowel diseases (IBDs), where case series demonstrated a successful treatment of CDI by FMT in 83-92% of patients. The effect of FMT on the activity of IBD has mainly been investigated in ulcerative colitis (UC) patients, including 3 randomized controlled trials. So far, 2 randomized controlled trials showed a superiority of FMT compared to placebo in inducing remission in UC, while 1 study found no significant difference to placebo. The variation in response to FMT between these studies as well as in the uncontrolled trials might be explained by many differences in the way of FMT application, patient pretreatment and patient and donor selection. The data for the use of FMT in Crohn's disease and pouchitis are sparse; currently, no conclusion can be drawn regarding the effectiveness of FMT in these indications. It needs to be noted that cases of IBD activation after FMT have been reported. So far, FMT can only be recommended to be used for the treatment of concomitant CDI in IBD in clinical practice. For treating IBD irrespective of CDI, FMT should be only used in clinical trials. Current forms of FMT, especially protocols using repeated application, are very time and personnel consuming. Future trends are the use of defined stable microbiota preparations, in particular oral preparations, which will enable better and larger controlled trails for investigating FMT in IBD. © 2016 S. Karger AG, Basel.

  1. Primary Ciliary Dyskinesia: An Update on Clinical Aspects, Genetics, Diagnosis, and Future Treatment Strategies

    PubMed Central

    Mirra, Virginia; Werner, Claudius; Santamaria, Francesca

    2017-01-01

    Primary ciliary dyskinesia (PCD) is an orphan disease (MIM 244400), autosomal recessive inherited, characterized by motile ciliary dysfunction. The estimated prevalence of PCD is 1:10,000 to 1:20,000 live-born children, but true prevalence could be even higher. PCD is characterized by chronic upper and lower respiratory tract disease, infertility/ectopic pregnancy, and situs anomalies, that occur in ≈50% of PCD patients (Kartagener syndrome), and these may be associated with congenital heart abnormalities. Most patients report a daily year-round wet cough or nose congestion starting in the first year of life. Daily wet cough, associated with recurrent infections exacerbations, results in the development of chronic suppurative lung disease, with localized-to-diffuse bronchiectasis. No diagnostic test is perfect for confirming PCD. Diagnosis can be challenging and relies on a combination of clinical data, nasal nitric oxide levels plus cilia ultrastructure and function analysis. Adjunctive tests include genetic analysis and repeated tests in ciliary culture specimens. There are currently 33 known genes associated with PCD and correlations between genotype and ultrastructural defects have been increasingly demonstrated. Comprehensive genetic testing may hopefully screen young infants before symptoms occur, thus improving survival. Recent surprising advances in PCD genetic designed a novel approach called “gene editing” to restore gene function and normalize ciliary motility, opening up new avenues for treating PCD. Currently, there are no data from randomized clinical trials to support any specific treatment, thus, management strategies are usually extrapolated from cystic fibrosis. The goal of treatment is to prevent exacerbations, slowing the progression of lung disease. The therapeutic mainstay includes airway clearance maneuvers mainly with nebulized hypertonic saline and chest physiotherapy, and prompt and aggressive administration of antibiotics

  2. Future Workforce Strategy

    ERIC Educational Resources Information Center

    US Department of Energy, 2007

    2007-01-01

    The Department of Energy's (DOE) Office of Science is among the world's premier supporters of basic research. The Office of Science enables the U.S. to maintain its competitive edge by funding science that can transform its energy future, supports its national security and seeks to understand the fundamentals of matter and energy itself. To do…

  3. Strategies for targeted drug delivery in treatment of colon cancer: current trends and future perspectives.

    PubMed

    Banerjee, Antara; Pathak, Surajit; Subramanium, Vimala Devi; G, Dharanivasan; Murugesan, Ramachandran; Verma, Rama S

    2017-08-01

    Despite advances in treatment modalities, colon cancer (CC) is the third most common cause of cancer-related death worldwide. Subsequent unfavorable effects owing to toxicity of conventional drugs are a challenging problem associated with chemotherapy. There is noticeable concern toward site-specific/targeted delivery of chemotherapeutic drugs specifically to the affected site of the colon in a predictable and reproducible manner. However, the biggest challenge in successful drug targeting for the colon is avoidance of drug absorption and/or degradation in the upper gastrointestinal tract before the drug reaches the colon. Nanoparticles endowed with targeting abilities offer a novel approach for site-specific delivery of chemotherapeutic agents. The present review focuses on recent approaches for colon-specific drug delivery (CDDS) and aims to unveil the emerging possibilities and advances in the treatment of CC with CDDS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Current and Future Percutaneous Strategies for the Treatment of Acute and Chronic Heart Failure.

    PubMed

    Amat-Santos, Ignacio J; Varela-Falcón, Luis H; Abraham, William T

    2017-01-30

    The prevalence of heart failure (HF) has risen in parallel with improved survival in patients after a myocardial infarction and an aging population worldwide. In recent years, new percutaneous therapies have been developed to complement current established treatments for acute/decompensated and chronic HF and minimize risks. In acute presentations, the failure of medical treatment is no longer the end of the road in refractory circulatory shock; the use of mechanical circulatory support devices may be the next milestone in well-resourced health settings. Although evidence in this area is difficult to generate, research networks can facilitate the volume and quality of data needed to further augment the clinician's knowledge. Pulsatile (intra-aortic balloon pump), axial continuous (Impella), or centrifugal continuous pumps (TandemHeart; HeartMate PHP) together with percutaneously implanted extracorporeal membrane oxygenation are radically changing the prognosis of acute HF. Newer percutaneous therapies for chronic HF are based on attractive hypotheses, including left atrial decompression with shunting devices, left ventricle restoration through partitioning devices, or pressure-guided implantable therapies that may help to promptly treat decompensations. To date, only the last has been proved effective in a randomized study. Therefore, thorough research is still needed in this dynamic and promising field.

  5. Pancreatic Neuroendocrine Neoplasms: Basic Biology, Current Treatment Strategies and Prospects for the Future.

    PubMed

    Ohmoto, Akihiro; Rokutan, Hirofumi; Yachida, Shinichi

    2017-01-13

    Pancreatic neuroendocrine neoplasms (pNENs) are rare tumors accounting for only 1%-2% of all pancreatic tumors. pNENs are pathologically heterogeneous and are categorized into three groups (neuroendocrine tumor: NET G1, NET G2; and neuroendocrine carcinoma: NEC) on the basis of the Ki-67 proliferation index and the mitotic count according to the 2010 World Health Organization (WHO) classification of gastroenteropancreatic NENs. NEC in this classification includes both histologically well-differentiated and poorly differentiated subtypes, and modification of the WHO 2010 classification is under discussion based on genetic and clinical data. Genomic analysis has revealed NETs G1/G2 have genetic alterations in chromatin remodeling genes such as MEN1, DAXX and ATRX, whereas NECs have an inactivation of TP53 and RB1, and these data suggest that different treatment approaches would be required for NET G1/G2 and NEC. While there are promising molecular targeted drugs, such as everolimus or sunitinib, for advanced NET G1/G2, treatment stratification based on appropriate predictive and prognostic biomarkers is becoming an important issue. The clinical outcome of NEC is still dismal, and a more detailed understanding of the genetic background together with preclinical studies to develop new agents, including those already under investigation for small cell lung cancer (SCLC), will be needed to improve the prognosis.

  6. Neprilysin inhibition: A brief review of past pharmacological strategies for heart failure treatment and future directions.

    PubMed

    Howell, Erik H; Cameron, Scott J

    2016-01-01

    Heart failure (HF) is a manifestation of aberrant vascular responses and remains a public health concern with a worldwide prevalence of around 23 million and a 5-year mortality numerically equivalent to many cancers. Over the last two decades, mortality from HF reached a plateau with current pharmaceutical agents and mechanical cardiac support. In the last several years, various "novel" pharmaceutical agents have been tested in clinical trials and ultimately met with disappointment, showing only incremental benefit in the treatment of HF. Designing a HF drug with enhanced efficacy over existing agents seemed like a Sisyphean task. Yet again, pharmaceutical chemists have demonstrated their prowess in lateral thinking by developing a vasoactive agent which is a co-crystallized compound of valsartan and sacubitril in a one-to-one molar ratio; the former molecule belongs to a family of agents that are the current standard of care for HF and the latter molecule is a novel agent which inhibits neprilysin - a neutral endopeptidase found in human plasma which alters neurohumoral responses. In July of 2015, a drug which is a combination of valsartan and sacubitril was formally licensed by the United States Food and Drug Administration for the treatment of HF. This review describes the evolution of HF medications focusing on rational drug design with the first HF medication, the beta-adrenergic receptor antagonist. We then discuss the biochemical and physiological properties of sacubitril/valsartan which likely lead to its dramatic ability to ameliorate HF mortality.

  7. Pancreatic Neuroendocrine Neoplasms: Basic Biology, Current Treatment Strategies and Prospects for the Future

    PubMed Central

    Ohmoto, Akihiro; Rokutan, Hirofumi; Yachida, Shinichi

    2017-01-01

    Pancreatic neuroendocrine neoplasms (pNENs) are rare tumors accounting for only 1%–2% of all pancreatic tumors. pNENs are pathologically heterogeneous and are categorized into three groups (neuroendocrine tumor: NET G1, NET G2; and neuroendocrine carcinoma: NEC) on the basis of the Ki-67 proliferation index and the mitotic count according to the 2010 World Health Organization (WHO) classification of gastroenteropancreatic NENs. NEC in this classification includes both histologically well-differentiated and poorly differentiated subtypes, and modification of the WHO 2010 classification is under discussion based on genetic and clinical data. Genomic analysis has revealed NETs G1/G2 have genetic alterations in chromatin remodeling genes such as MEN1, DAXX and ATRX, whereas NECs have an inactivation of TP53 and RB1, and these data suggest that different treatment approaches would be required for NET G1/G2 and NEC. While there are promising molecular targeted drugs, such as everolimus or sunitinib, for advanced NET G1/G2, treatment stratification based on appropriate predictive and prognostic biomarkers is becoming an important issue. The clinical outcome of NEC is still dismal, and a more detailed understanding of the genetic background together with preclinical studies to develop new agents, including those already under investigation for small cell lung cancer (SCLC), will be needed to improve the prognosis. PMID:28098761

  8. Neprilysin inhibition: a brief review of past pharmacological strategies for heart failure treatment and future directions

    PubMed Central

    Howell, Erik H.; Cameron, Scott J.

    2016-01-01

    Heart failure (HF) is a manifestation of aberrant vascular responses and remains a public health concern with a worldwide prevalence of around 23 million and a 5-year mortality numerically equivalent to many cancers. Over the last two decades, mortality from HF reached a plateau with current pharmaceutical agents and mechanical cardiac support. In the last several years, various “novel” pharmaceutical agents have been tested in clinical trials and ultimately met with disappointment, showing only incremental benefit in the treatment of HF. Designing a HF drug with enhanced efficacy over existing agents seemed like a Sisyphean task. Yet again, pharmaceutical chemists have demonstrated their prowess in lateral thinking by developing a vasoactive agent which is a co-crystallized compound of valsartan and sacubitril in a one-to-one molar ratio; the former molecule belongs to a family of agents that are the current standard of care for HF and the latter molecule is a novel agent which inhibits neprilysin — a neutral endopeptidase found in human plasma which alters neurohumoral responses. In July of 2015, a drug which is a combination of valsartan and sacubitril was formally licensed by the United States Food and Drug Administration for the treatment of HF. This review describes the evolution of HF medications focusing on rational drug design with the first HF medication, the beta adrenergic receptor antagonist. We then discuss the biochemical and physiological properties of sacubitril/valsartan which likely lead to its dramatic ability to ameliorate HF mortality. PMID:27665860

  9. Management of malignancy-associated pleural effusion: current and future treatment strategies.

    PubMed

    Marchi, Evaldo; Teixeira, Lisete R; Vargas, Francisco S

    2003-01-01

    Management of recurrent malignant pleural effusion, a common complication of malignancy, poses a challenge to clinicians. Although almost one century has elapsed since the introduction of the pleurodesis procedure, the ideal approach and best agent are still to be defined. Optimally, pleurodesis should be done at the bedside with a minimally invasive procedure, and suitable agents to achieve pleural symphysis should be inexpensive, available worldwide and free of adverse effects. To date, no substance completely fulfills these requirements. Silver nitrate should be considered for pleurodesis because of its low cost and ease of handling. Although talc has been used most frequently to induce pleurodesis, reports of death due to acute respiratory failure have raised concerns about the safety of this agent. Tetracycline, an effective alternative used in the past, is no longer commercially available. This agent has been substituted with derivatives of tetracycline, such as minocycline and doxycycline with success rates similar to those with tetracycline. Several antineoplastic agents have been injected into the pleural space with the aim of producing pleural symphysis, the most representative of this group being bleomycin. Recent knowledge of the molecular mechanisms involved in pleural inflammation has brought into focus new substances, such as transforming growth factor beta and vascular endothelial growth factor, which may be used as pleurodesis agents in the future. Nevertheless, more studies are necessary to better define the potential of these substances in the induction of pleural symphysis.Ideally, a sclerosing agent should be cost-effective, available worldwide and easily administered. Talc will probably stand as the preferred agent to be used for pleurodesis in malignant pleural effusion because of its efficacy, easy manipulation and handling. However, further investigation is necessary to minimize adverse effects related to talc.

  10. Future anti-HBV strategies.

    PubMed

    Gane, Edward J

    2017-01-01

    Although current oral antivirals can maintain viral suppression and reduce the risk of liver-related complications, lifelong therapy is associated with high cost, risk of breakthrough and potential toxicity. There is a need to develop a finite course of treatment which can provide sustained off-treatment virological and clinical response. The likely marker of such a clinical HBV CURE would be HBsAg clearance, but in addition cccDNA elimination would be required to prevent future reactivation (ie complete HBV cure). Chronic HBV infection is characterised by high viral and antigen burden and inadequate host immune responses, both of which will need to be overcome to achieve HBV CURE. Innovative approaches to restore innate and adaptive immune responses against HBV currently in clinical development include therapeutic vaccines, TLR-7 and TLR-8 agonists. In future, strategies to reverse T-cell exhaustion such as checkpoint inhibitors may be feasible. Currently, the only antivirals in clinical use are the HBV polymerase inhibitors. However, many other steps of HBV virion life cycle can be targeted by small molecules, including inhibitors of HBV entry, nucleocapsid formation and virion assembly and release. siRNAs could inhibit many different steps by blocking multiple HBV transcripts. But, the ultimate goal will be to successfully eradicate or silence cccDNA. It is likely that successful HBV cure will require combination of immunomodulatory, antiviral and cccDNA silencing strategies. Efficacy, safety, route of administration and cost will ultimately determine the impact of these new regimens on the burden of HBV. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Mind the (treatment) gap: a global perspective on current and future strategies for prevention of fragility fractures.

    PubMed

    Harvey, N C W; McCloskey, E V; Mitchell, P J; Dawson-Hughes, B; Pierroz, D D; Reginster, J-Y; Rizzoli, R; Cooper, C; Kanis, J A

    2017-05-01

    This narrative review considers the key challenges facing healthcare professionals and policymakers responsible for providing care to populations in relation to bone health. These challenges broadly fall into four distinct themes: (1) case finding and management of individuals at high risk of fracture, (2) public awareness of osteoporosis and fragility fractures, (3) reimbursement and health system policy and (4) epidemiology of fracture in the developing world. Findings from cohort studies, randomised controlled trials, systematic reviews and meta-analyses, in addition to current clinical guidelines, position papers and national and international audits, are summarised, with the intention of providing a prioritised approach to delivery of optimal bone health for all. Systematic approaches to case-finding individuals who are at high risk of sustaining fragility fractures are described. These include strategies and models of care intended to improve case finding for individuals who have sustained fragility fractures, those undergoing treatment with medicines which have an adverse effect on bone health and people who have diseases, whereby bone loss and, consequently, fragility fractures are a common comorbidity. Approaches to deliver primary fracture prevention in a clinically effective and cost-effective manner are also explored. Public awareness of osteoporosis is low worldwide. If older people are to be more pro-active in the management of their bone health, that needs to change. Effective disease awareness campaigns have been implemented in some countries but need to be undertaken in many more. A major need exists to improve awareness of the risk that osteoporosis poses to individuals who have initiated treatment, with the intention of improving adherence in the long term. A multisector effort is also required to support patients and their clinicians to have meaningful discussions concerning the risk-benefit ratio of osteoporosis treatment. With regard to

  12. National Strategy, Future Threats and Defense Spending

    DTIC Science & Technology

    1992-06-05

    AD-A256 884 NATIONAL STRATEGY, FUTURE THREATS AND DEFENSE SPENDING A thesis presented to the Faculty of the U.S. Army Command and General Staff...Jun 92 4. TITLE AND SUBTITLE S. FUNDING NUMBERS National Strategy, Future Threats and Defense Spending 6. AUTHOR(S) MAJ Daniel M. Gerstein, USA 7...Future Threats, Defense Spending , 192 Regional Threats 16. PRICE COOE 17. SECURITY CLASSIFICATION 118. SECURITY CLASSIFICATION 19. SECURITY

  13. Treatment of venous thromboembolism - effects of different therapeutic strategies on bleeding and recurrence rates and considerations for future anticoagulant management.

    PubMed

    Hass, Bastian; Pooley, Jayne; Harrington, Adrian E; Clemens, Andreas; Feuring, Martin

    2012-12-31

    Effective treatment of venous thromboembolism (VTE) strikes a balance between prevention of recurrence and bleeding complications. The current standard of care is heparin followed by a vitamin K antagonist such as warfarin. However, this option is not without its limitations, as the anticoagulant effect of warfarin is associated with high inter- and intra-patient variability and patients must be regularly monitored to ensure that anticoagulation is within the narrow target therapeutic range. Several novel oral anticoagulant agents are in the advanced stages of development for VTE treatment, some of which are given after an initial period of heparin treatment, in line with current practice, while others switch from high to low doses after the initial phase of treatment. In this review we assess the critical considerations for treating VTE in light of emerging clinical data for new oral agents and discuss the merits of novel treatment regimens for patients who have experienced an episode of deep vein thrombosis or pulmonary embolism.

  14. Biventricular pacing: current trends and future strategies.

    PubMed

    Singh, Jagmeet P; Gras, Daniel

    2012-02-01

    The role of biventricular pacing is expanding beyond the New York Heart Association classes III and IV heart failure (HF) patient to include less symptomatic patients, earlier in the course of their disease process. This multisite pacing strategy has substantially altered the natural course of ventricular failure, exerting its physiological impact through favourable cardiac remodelling and improving the ejection fraction. This has in turn resulted in long-term clinical benefits such as improved quality of life and functional capacity with a concomitant reduction in hospitalization for HF and overall mortality. Despite the successes of cardiac resynchronization therapy (CRT) and the recent expansion of its role in the treatment of HF patients, there remain some inherent limitations to the technology and its delivery. A significant minority of patients continue to remain non-responsive to this pacing strategy. This review will highlight biventricular pacing in its present form, will elaborate on strategies to enhance response to CRT, and outline future trends and synergies towards maximizing the potential benefit of this therapeutic modality.

  15. Future treatment of osteoarthritis.

    PubMed

    Baker, Champ L; Ferguson, Cristin M

    2005-02-01

    Osteoarthritis represents an advanced stage of disease progression caused in part by injury, loss of cartilage structure and function, and an imbalance in inflammatory and noninflammatory pathways. The burden of this disease will increase in direct proportion to the increase in the older adult population. Research on current and experimental treatment protocols are reviewed, including the effect of hyaluronic acid in both in vitro and in vivo studies, autologous chondrocyte and osteochondral plug implantation, and gene therapy. Disease-modifying osteoarthritis drugs and in vivo studies of glucosamine and chondroitin sulfate are reviewed.

  16. Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza. Part II: Future compounds against influenza virus.

    PubMed

    Gasparini, R; Amicizia, D; Lai, P L; Bragazzi, N L; Panatto, D

    2014-12-01

    In the first part of this overview, we described the life cycle of the influenza virus and the pharmacological action of the currently available drugs. This second part provides an overview of the molecular mechanisms and targets of still-experimental drugs for the treatment and management of influenza. Briefly, we can distinguish between compounds with anti-influenza activity that target influenza virus proteins or genes, and molecules that target host components that are essential for viral replication and propagation. These latter compounds have been developed quite recently. Among the first group, we will focus especially on hemagglutinin, M2 channel and neuraminidase inhibitors. The second group of compounds may pave the way for personalized treatment and influenza management. Combination therapies are also discussed. In recent decades, few antiviral molecules against influenza virus infections have been available; this has conditioned their use during human and animal outbreaks. Indeed, during seasonal and pandemic outbreaks, antiviral drugs have usually been administered in mono-therapy and, sometimes, in an uncontrolled manner to farm animals. This has led to the emergence of viral strains displaying resistance, especially to compounds of the amantadane family. For this reason, it is particularly important to develop new antiviral drugs against influenza viruses. Indeed, although vaccination is the most powerful means of mitigating the effects of influenza epidemics, antiviral drugs can be very useful, particularly in delaying the spread of new pandemic viruses, thereby enabling manufacturers to prepare large quantities of pandemic vaccine. In addition, antiviral drugs are particularly valuable in complicated cases of influenza, especially in hospitalized patients. To write this overview, we mined various databases, including Embase, PubChem, DrugBank and Chemical Abstracts Service, and patent repositories.

  17. Treatment strategies for endometriosis.

    PubMed

    Rodgers, Allison K; Falcone, Tommaso

    2008-02-01

    Endometriosis is a common chronic disease that causes symptoms of pain and infertility. The pain syndrome can be quite incapacitating. The pain symptoms usually originate in the reproductive organs but can also involve the urinary or intestinal tracts if endometriosis implantation has occurred there. The presentation and physical appearance of endometriosis is extremely variable and can be characterized by a chronic intraperitoneal inflammatory process and adhesions. The only definitive diagnostic technique is laparoscopy. To review current literature on the treatment strategies for endometriosis. Review of Pubmed, Cochrane database and Medline for current review articles and studies regarding the current treatment strategies for endometriosis. Initial treatment is surgical or medical. Medical therapy is often used as a first-line therapy and can also be used in conjunction with those patients who undergo surgical therapy for pain. No medical therapy has proven effective for infertility. Medical therapy consists mostly of hormonal suppressive therapy in which the medication causes a downregulation of the hypothalamus-pituitary-ovarian pathway. Non-steroidal anti-inflammatory drugs and oral contraceptives are often used as an initial approach even without a definitive diagnosis. Progestins, such as oral norethindrone and depot medroxyprogesterone, are effective while using them but have a high recurrence rate. The norgestrol intrauterine device is also quite effective at relieving pain associated with endometriosis, especially pain arising during menses as well as from lesions in the rectovaginal tissue. Gonadotropin-releasing hormone agonists induce a pseudomenopausal state and have significant side effects, such as hot flashes and genital atrophy. 'Add-back' therapy with a progestin has been shown to relieve most of these drug related symptoms. Gonadotropin-releasing hormone agonists are also very effective at relieving symptoms of pain during treatment but are

  18. Future directions in multiple myeloma treatment.

    PubMed

    Child, J Anthony; Russell, Nigel; Sonneveld, Pieter; Schey, Steve

    2005-01-01

    Future therapy options for multiple myeloma may be directed at asymptomatic disease, as only symptomatic myeloma is treated currently. Additional genetic information from gene array analysis will mean that the identification of cases with poor prognosis will become more sophisticated. New markers are being discovered constantly, and these continuously change the picture regarding prognostic factors. More intensive treatment options increase the depth of remissions, thereby improving outcomes. In pilot studies, cyclophosphamide, thalidomide and dexamethasone (CTD) was a highly effective, well-tolerated regimen for patients refractory to initial therapy with VAD or with relapsed disease. It is being further evaluated as induction therapy in the current MRC Myeloma IX trial. Also under investigation is a small molecule derivative of thalidomide, CC-4047 (Actimid). It has between 1,000 and 10,000 times more potent antitumour necrosis factor alpha activity, with an additional immunomodulatory effect. It has been shown to be between 50 and 2,000 times more potent in the stimulation of T-cell proliferation and 50-100 times more potent in augmenting interleukin-2 and interferon-gamma production. With many possible approaches to study and work through, future strategies will revolve around exploration of the effectiveness of combinations that incorporate new agents in various disease and treatment settings. The use of genetic profiles to further delineate groups for different treatment approaches should enable the introduction of patient-specific treatment programmes in the future.

  19. Stem cell strategies, future and beyond.

    PubMed

    Sugaya, Kiminobu

    2003-01-01

    The use of stem cells for neuroreplacement therapy is no longer science fiction--it is science fact. We have succeeded in the development of neural and mesenchymal stem cell transplantation to produce neural cells in the brain. We have seen the improvement of cognitive function in a memory-impaired aged animal model following stem cell transplantation. These results may promise a bright future for stem cell strategies. Before we begin to think about clinical applications beyond the present preclinical studies or even consider the pathophysiological environments of individual diseases, we must address and weigh the factors that may affect stem cell biology. Here, we not only show the potential for therapeutic applications for stem cell strategies in neuropathological conditions, but we also discuss the effects on the biology of stem cells of those factors that are altered under disease conditions.

  20. [Osteoporosis: Optimizing treatment strategy].

    PubMed

    Thomas, Thierry

    2006-10-01

    Selection of patients for treatment is based on the assessment of their absolute fracture risk over 10 years. Assessment of fracture risk includes not only DXA measurement and age, the two principal risk factors, but also other clinical risk factors. The main goal of postmenopausal osteoporosis treatment is to reduce the risk of fragility fractures. Choice of treatment is based on drug properties, demonstrated in clinical trials, and patients' specific fracture risks. The minimum duration of treatment is 4-5 years, after which individual fracture risk must be reevaluated. Combinations of available drugs are not recommended for treatment of postmenopausal osteoporosis.

  1. Prevention strategies for cardioembolic stroke: present and future perspectives.

    PubMed

    Giacalone, Giacomo; Abbas, Mohammed Abballa; Corea, Francesco

    2010-06-15

    Atrial fibrillation (AF) is the most common cause of cardioembolism. An update on secondary prevention strategies, used to protect patients from the risk of stroke in many common cardiac conditions, is presented in the paper. The main line of actions of stroke prevention in cardioembolism is mostly connected with antithrombotic drugs, but also other, more invasive, techniques are quickly emerging. Also the classic pharmacological prevention with coumarins may soon be overcome by new generation anticoagulants. Is an aggressive treatment of Patent Foramen Ovale (PFO) always recommended? One of the main challenges of the future years will be to understand competitiveness between old and new preventive strategies.

  2. Treatment strategies for dystonia

    PubMed Central

    Cloud, Leslie J; Jinnah, HA

    2012-01-01

    Importance of the field Dystonia is a neurological syndrome characterized by involuntary twisting movements and unnatural postures. It has many different manifestations and causes, and many different treatment options are available. These options include physical and occupational therapy, oral medications, intramuscular injection of botulinum toxins, and neurosurgical interventions. Areas covered in this review In this review, we first summarize the treatment options available, then we provide suggestions from our own experience for how these can be applied in different types of dystonia. In preparing this review article, an extensive literature search was undertaken using PubMed. Only selected references from 1970 to 2008 are cited. What the reader will gain This review is intended to provide the clinician with a practical guide to the treatment of dystonia. Take home message Treatment of dystonia begins with proper diagnosis and classification, followed by an appropriate search for underlying etiology, and an assessment of the functional impairment associated with the dystonia. The therapeutic approach, which is usually limited to symptomatic therapy, must then be tailored to the individual needs of the patient. PMID:20001425

  3. Future launchers strategy : the ariane 2010 initiative

    NASA Astrophysics Data System (ADS)

    Bonnal, Ch.; Eymard, M.; Soccodato, C.

    2001-03-01

    With the new cryogenic upper stage ESC, the European heavy launcher Ariane 5+ is perfectly suited to the space market envisioned for the coming decade: flexible to cope with any payload and commercially attractive despite a fierce competition. Current Arianespace projections for the following years 2010-2020 indicate two major trends: satellites may still become larger and may require very different final orbits; today's market largely dominated by GEO may well evolve, influenced by LEO operations such as those linked to ISS or by constellations, to remain competitive, the launch cost has to be reduced. The future generation of the European heavy launcher has therefore to focus on an ever increased flexibility with a drastic cost reduction. Two strategies are possible to achieve this double goal: reusable launchers, either partially or totally, may ease the access to space, limiting costly expendable stages; the assessment of their technical feasibility and financial viability is undergoing in Europe under the Future Launchers Technology Program (FLTP), expendable launchers, derived from the future Ariane 5+. This second way started by CNES at the end of year 1999 is called the "Ariane 2010 initiative". The main objectives are simultaneously an increase of 25% in performance and a reduction of 30% in launch cost wrt Ariane 5+. To achieve these very ambitious goals, numerous major modifications are studied: technical improvements : modifications of the Solid Rocket Boosters may consist in filament winding casing, increased loading, simplified casting, improved grain, simplified Thrust Vector Control, … evolution of the Vulcain engine leading to higher efficiency despite a simplified design, flow separation controlled nozzle extension, propellant management of the two cryogenic stages, simplified electrical system, increased standardization, for instance on flanged interfaces and manufacturing processes, operational improvements such as launch cycle simplification

  4. Towards a rAAV-based gene therapy for ADA-SCID: from ADA deficiency to current and future treatment strategies.

    PubMed

    Silver, Jared N; Flotte, Terence R

    2008-07-01

    Adenosine deaminase deficiency fosters a rare, devastating pediatric immune deficiency with concomitant opportunistic infections, metabolic anomalies and multiple organ system pathology. The standard of care for adenosine deaminase deficient severe combined immune deficiency (ADA-SCID) includes enzyme replacement therapy or bone marrow transplantation. Gene therapies for ADA-SCID over nearly two decades have exclusively involved retroviral vectors targeted to lymphocytes and hematopoetic progenitors. These groundbreaking gene therapies represent a revolution in clinical medicine, but come with several challenges, including the risk of insertional mutagenesis. An alternative gene therapy for ADA-SCID may utilize recombinant adeno-associated virus vectors in vivo, with numerous target tissues, to foster ectopic expression and secretion of adenosine deaminase. This review endeavors to describe ADA-SCID, the traditional treatments, previous retroviral gene therapies, and primarily, alternative recombinant adeno-associated virus-based strategies to remedy this potentially fatal genetic disease.

  5. Melasma: treatment strategy.

    PubMed

    Sehgal, Virendra N; Verma, Prashant; Srivastava, Govind; Aggarwal, Ashok K; Verma, Sangeeta

    2011-12-01

    Melasma, a hypermelanosis of the face, is a common skin problem of middle-aged women of all racial groups, especially with dark complexion. Its precise etio-pathogenesis is evasive, genetic influences, exposure to sunlight, pregnancy, oral contraceptives, estrogen-progesterone therapies, thyroid dysfunction, cosmetics, and drugs have been proposed. Centro-facial, malar, and mandibular are well-recognized. Epidermal pigmentation appears brown/black, while dermal is blue in color, and can be distinguished by Wood's lamp illumination. The difference may be inapparent with mixed type of melasma in skin types V and VI. An increase in melanin in epidermis: basal and suprabasal layers and/or dermis is the prime defect. There is an increased expression of tyrosinase related protein-1 involved in eumelanin synthesis. The use of broad-spectrum sunscreen is important, lightening agents like retinoic acid (tretinoin), azelaic acid, and combination therapies containing hydroquinone, tretinoin, and corticosteroids, have been used in the treatment of melasma, and are thought to have increased efficacy as compared with monotherapy. Quasi-drugs, placental extracts, ellagic acid, chamomilla extract, butylresorcinol, tranexamic acid, methoxy potassium salicylate, adenosine monophosphate disodium salt, dipropyl-biphenyl-2,2'-diol, (4-hydroxyphenyl)-2-butanol, and tranexamic acid cetyl ester hydrochloride, in addition to kojic and ascorbic acid have been used. Chemical peeling is a good adjunct. Laser treatment is worthwhile.

  6. The European Organization for Research and Treatment for Cancer (EORTC) strategy for quality assurance in surgical clinical research: Assessment of the past and moving towards the future.

    PubMed

    Tanis, E; Caballero, C; Collette, L; Verleye, L; den Dulk, M; Lacombe, D; Schuhmacher, C; Werutsky, G

    2016-08-01

    Quality assurance (QA) in a surgical trial must be planned and implemented from study development to completion. Elements of quality must be consistently described in a protocols, case report forms (CRFs) and reported in publications. The purpose of this review was to evaluate the most common surgical parameters and how consistently they were described in EORTC study documents where surgery was included. This was the preliminary step in mapping out the challenges of developing a surgical QA strategy in EORTC. A systematic review of EORTC surgical protocols from 1980 to 2013 was performed. Two independent reviewers selected and reviewed the protocols. Data extraction was done using a questionnaire developed by EORTC QA committee. The results were compared across the time period. The most common quality parameters described in protocols were surgical technique, definition of resectability, surgical margins and methods of assessing adverse events using the Common Terminology Criteria for Adverse Event (CTCAE). However, these were not consistently reported in publications. A general improvement in the method of protocol development was observed since year 2000 after standardization measures by EORTC. A new surgical chapter template has been proposed. There is a need to consistently define and report surgical parameters from protocol development to publication as a first step to QA. A standard surgical chapter in the EORTC protocol template can help address this need. A framework to consistently implement QA for future surgical trials is needed and the rationale for this is described in this review. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Cultural psychiatry: research strategies and future directions.

    PubMed

    Kirmayer, Laurence J; Ban, Lauren

    2013-01-01

    This chapter reviews some key aspects of current research in cultural psychiatry and explores future prospects. The first section discusses the multiple meanings of culture in the contemporary world and their relevance for understanding mental health and illness. The next section considers methodological strategies for unpacking the concept of culture and studying the impact of cultural variables, processes and contexts. Multiple methods are needed to address the many different components or dimensions of cultural identity and experience that constitute local worlds, ways of life or systems of knowledge. Quantitative and observational methods of clinical epidemiology and experimental science as well as qualitative ethnographic methods are needed to capture crucial aspects of culture as systems of meaning and practice. Emerging issues in cultural psychiatric research include: cultural variations in illness experience and expression; the situated nature of cognition and emotion; cultural configurations of self and personhood; concepts of mental disorder and mental health literacy; and the prospect of ecosocial models of health and culturally based interventions. The conclusion considers the implications of the emerging perspectives from cultural neuroscience for psychiatric theory and practice.

  8. Yukon Training Strategy. Training for the Future.

    ERIC Educational Resources Information Center

    Yukon Dept. of Education, White Horse.

    This document was created as part of "Yukon 2000," a Yukon government initiative for steering social and economic growth. The expressed intent of the training strategy is to direct government efforts toward preparing people for existing and potential employment in the Yukon. In some areas, the strategy confirms program directions already…

  9. Current therapeutic strategies for premature ejaculation and future perspectives

    PubMed Central

    Xin, Zhong-Cheng; Zhu, Yi-Chen; Yuan, Yi-Ming; Cui, Wan-Shou; Jin, Zhe; Li, Wei-Ren; Liu, Tao

    2011-01-01

    Premature ejaculation (PE) is a common sexual disorder in men that is mediated by disturbances in the peripheral and central nervous systems. Although all pharmaceutical treatments for PE are currently used ‘off-label', some novel oral agents and some newer methods of drug administration now provide important relief to PE patients. However, the aetiology of this condition has still not been unified, primarily because of the lack of a standard animal model for basic research and the absence of a widely accepted definition and assessment tool for evidence-based clinical studies in patients with PE. In this review, we focus on the current therapeutic strategies and future treatment perspectives for PE. PMID:21532601

  10. Beyond the Horizon: Developing Future Airpower Strategy

    DTIC Science & Technology

    2014-01-01

    advantageous. Furthermore, as the world becomes more interconnected; as media and technology provide the vehicle to share massive amounts of live or near- live ... streaming video; and as social media capabilities continue to connect more people, the future scrutiny of “collateral damage” during strategic

  11. Cellular Learning: Strategy for the Future.

    ERIC Educational Resources Information Center

    Schrum, John

    1987-01-01

    Cellular learning refers to both arrangement of shop equipment and addition of new course materials for a contemporary manufacturing curriculum. The concept is an accumulation of ideas and strategies for the instruction and training of students. It also provides a method for consolidating old equipment and adding group technology. (CH)

  12. Genetic medicines: treatment strategies for hereditary disorders.

    PubMed

    O'Connor, Timothy P; Crystal, Ronald G

    2006-04-01

    The treatment of the more than 1,800 known monogenic hereditary disorders will depend on the development of 'genetic medicines' - therapies that use the transfer of DNA and/or RNA to modify gene expression to correct or compensate for an abnormal phenotype. Strategies include the use of somatic stem cells, gene transfer, RNA modification and, in the future, embryonic stem cells. Despite the efficacy of these technologies in treating experimental models of hereditary disorders, applying them successfully in the clinic is a great challenge, which will only be overcome by expending considerable intellectual and economic resources, and by solving societal concerns about modifications of the human genetic repertoire.

  13. Current and future treatment of amyloid diseases

    PubMed Central

    Ankarcrona, M.; Winblad, B.; Monteiro, C.; Fearns, C.; Powers, E. T.; Johansson, J.; Westermark, G. T.; Presto, J.; Ericzon, B-G.; Kelly, J. W.

    2016-01-01

    There are more than 30 human proteins whose aggregation appears to cause degenerative maladies referred to as amyloid diseases or amyloidoses. These disorders are named after the characteristic cross-β-sheet amyloid fibrils that accumulate systemically or are localized to specific organs. In most cases current treatment is limited to symptomatic approaches and thus disease-modifying therapies are needed. Alzheimer’s disease is a neurodegenerative disorder with amyloid β-peptide (Aβ) plaques and tau neurofibrillary tangles as pathological hallmarks. Numerous clinical trials have been conducted with vaccines and small molecules to target Aβ formation and aggregation and also enhance Aβ clearance; so far such clinical trials have been unsuccessful. Novel strategies are therefore required and here we will discuss the possibility of utilizing the chaperone BRICHOS to prevent Aβ aggregation and toxicity. Type 2 diabetes mellitus is symptomatically treated with insulin. However the disease is linked to the aggregation and progressive accumulation of islet amyloid polypeptide and oligomers of this peptide are cytotoxic. Several compounds have been shown to inhibit islet amyloid aggregation and cytotoxicity in vitro. Future animal studies and clinical trials have to be be conducted to determine their efficacy in vivo. Transthyretin (TTR) amyloidoses are a group of systemic degenerative diseases involving multiple organ systems and caused by TTR aggregation. Liver transplantation decreases the generation of misfolded TTR and improves the quality of life for a subgroup of this patient population. Compounds that stabilize the natively folded, non-amyloidogenic, tetrameric conformation of TTR have been developed and the drug tafamidis is available as treatment. PMID:27165517

  14. Current and future treatment of amyloid diseases.

    PubMed

    Ankarcrona, M; Winblad, B; Monteiro, C; Fearns, C; Powers, E T; Johansson, J; Westermark, G T; Presto, J; Ericzon, B-G; Kelly, J W

    2016-08-01

    There are more than 30 human proteins whose aggregation appears to cause degenerative maladies referred to as amyloid diseases or amyloidoses. These disorders are named after the characteristic cross-β-sheet amyloid fibrils that accumulate systemically or are localized to specific organs. In most cases, current treatment is limited to symptomatic approaches and thus disease-modifying therapies are needed. Alzheimer's disease is a neurodegenerative disorder with extracellular amyloid β-peptide (Aβ) fibrils and intracellular tau neurofibrillary tangles as pathological hallmarks. Numerous clinical trials have been conducted with passive and active immunotherapy, and small molecules to inhibit Aβ formation and aggregation or to enhance Aβ clearance; so far such clinical trials have been unsuccessful. Novel strategies are therefore required and here we will discuss the possibility of utilizing the chaperone BRICHOS to prevent Aβ aggregation and toxicity. Type 2 diabetes mellitus is symptomatically treated with insulin. However, the underlying pathology is linked to the aggregation and progressive accumulation of islet amyloid polypeptide as fibrils and oligomers, which are cytotoxic. Several compounds have been shown to inhibit islet amyloid aggregation and cytotoxicity in vitro. Future animal studies and clinical trials have to be conducted to determine their efficacy in vivo. The transthyretin (TTR) amyloidoses are a group of systemic degenerative diseases compromising multiple organ systems, caused by TTR aggregation. Liver transplantation decreases the generation of misfolded TTR and improves the quality of life for a subgroup of this patient population. Compounds that stabilize the natively folded, nonamyloidogenic, tetrameric conformation of TTR have been developed and the drug tafamidis is available as a promising treatment.

  15. Multimedia strategy considers waste treatment

    SciTech Connect

    Phillips, J.B.

    1995-05-01

    The advent of multimedia pollution prevention programs has raised some interesting and challenging questions on the subject of facility operations. First and foremost is the goal of a multimedia pollution prevention program: how can industrial streams in an operating facility be treated to prevent pollutants from escaping in a particular effluent or waste streams without transferring the same pollutants to another medium? Once this is resolved, the next issue to be addressed is the fate of pollutants removed from effluent streams. EPA is moving toward discouraging destruction as an acceptable means of waste treatment. The strategies are presented for handling pollutants from one media without contaminating another.

  16. New and future strategies to improve asthma control in children.

    PubMed

    Anderson, William C; Szefler, Stanley J

    2015-10-01

    Symptomatic asthma in childhood has lifelong effects on lung function and disease severity, emphasizing the need for improved pediatric asthma control. Control of pediatric risk and impairment domains can be achieved through increased medication adherence or new therapeutic strategies. Developing electronic monitoring device technology with reminders might be a key noninvasive resource to address poor adherence in children and adolescents in a clinical setting. In patients who have persistently poor control despite optimal medication compliance, newly emerging pharmaceuticals, including inhaled therapies and biologics, might be key to their treatment. However, barriers exist to their development in the pediatric population, and insights must be drawn from adult studies, which has its own unique limitations. Biomarkers to direct the use of such potentially expensive therapies to those patients most likely to benefit are imperative. In this review the current literature regarding strategies to improve pediatric asthma control is addressed with the goal of exploring the potential and pitfalls of strategies that might be available in the near future.

  17. Update on Treatment Strategies for Obesity

    PubMed Central

    2013-01-01

    Obesity is a disease that is defined as the accumulation of excessive amounts of body fat and is associated with increased risk of serious illness, disability, and death. In clinical practice, obesity is best assessed by calculating body mass index and measuring waist circumference. Treatment options are determined based on the body mass index, waist circumference, and adverse health consequences the patient is experiencing or is at an increased risk for facing in the future. Today, overweight and obesity impacts the majority of patients we treat in our clinical practices. Although endocrinologists are uniquely positioned to treat one of the major consequences of our current obesity epidemic, type 2 diabetes, we also need to be positioned and prepared to effectively treat one of its major causes—obesity. Type 2 diabetes and obesity are very much intertwined. Treatment of each disease affects the other. For these reasons, endocrinologists need to be experts in the treatment of obesity as well as diabetes. They should keep up with advances in obesity treatment including lifestyle, pharmaceutical, and surgical strategies. These strategies offer opportunities for improving the overall treatment for our obese patients today and will continue to improve and expand over the next decade. PMID:23443815

  18. [Strategies of treatment for febrile neutropenia].

    PubMed

    Terui, Yasuhito

    2013-06-01

    The guideline on febrile neutropenia(FN)was published by the Japanese Society of Medical Oncology(JSMO)in 2012. Based on this guideline, the treatment strategy for febrile neutropenia that is discussed in this paper includes empiric treatment strategies, methicillin-resistant Staphylococcus aureus antibiotics in the initial treatment, treatment for severe FN, treatment for outpatients, duration of FN treatment, treatment after recovery from fever associated with neutropenia, and empiric treatment with anti-fungal drugs in patients with prolonged FN.

  19. Tissue Engineering: Current Strategies and Future Directions

    PubMed Central

    Olson, Jennifer L.; Atala, Anthony

    2011-01-01

    Novel therapies resulting from regenerative medicine and tissue engineering technology may offer new hope for patients with injuries, end-stage organ failure, or other clinical issues. Currently, patients with diseased and injured organs are often treated with transplanted organs. However, there is a shortage of donor organs that is worsening yearly as the population ages and as the number of new cases of organ failure increases. Scientists in the field of regenerative medicine and tissue engineering are now applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that can restore and maintain normal function in diseased and injured tissues. In addition, the stem cell field is a rapidly advancing part of regenerative medicine, and new discoveries in this field create new options for this type of therapy. For example, new types of stem cells, such as amniotic fluid and placental stem cells that can circumvent the ethical issues associated with embryonic stem cells, have been discovered. The process of therapeutic cloning and the creation of induced pluripotent cells provide still other potential sources of stem cells for cell-based tissue engineering applications. Although stem cells are still in the research phase, some therapies arising from tissue engineering endeavors that make use of autologous, adult cells have already entered the clinical setting, indicating that regenerative medicine holds much promise for the future. PMID:22111050

  20. Powering nanorobotic devices: challenges and future strategies

    NASA Astrophysics Data System (ADS)

    Sankar, Krishna Moorthi

    2014-04-01

    Nanotechnology, even after 55 years since its foundation (1959 Richard Feynman's speech - `There is lot of space in the bottom'), is still in its infancy. However, of late, there has been a large increase in the research being done in this field in many prominent Universities and Research institutions across the globe. Nanorobotics is the combination of Nanotechnology and the science of Robotics, to create robots that are only a few nanometres (10-9 metres) in size. Nanobots are yet to be made. But with the current pace of ongoing researches, scientists predict that nanobots will be made a reality by next ten years. The main proposed function of nanobots is to use them in the medical field to interact with cells or intra-cellular substances and prevent or reverse structural and genetical problems and diseases. One of the major challenges faced while creating a nanobot to travel through human body is to power it. Nanobots would require a very small yet highly potential source of energy. There are many hypothesised energy sources for nanobots which are either already available within the human body naturally or which are to be supplied externally. But, all of these energy sources pose a few challenges which need to be addressed if they are to be used to power nanobots. These challenges can be overcome using a number of strategies that can be used to make an economically, ecologically and medically viable energy source.

  1. EMPA-REG and Other Cardiovascular Outcome Trials of Glucose-lowering Agents: Implications for Future Treatment Strategies in Type 2 Diabetes Mellitus.

    PubMed

    Schernthaner, Guntram; Schernthaner-Reiter, Marie Helene; Schernthaner, Gerit-Holger

    2016-06-01

    reduce the CV burden of patients with T2DM, drugs influencing factors involved in atherogenesis (eg, insulin resistance, chronic inflammation, increase of HDL, prothrombotic state) are more promising. The recent IRIS (Insulin Resistance Intervention after Stroke) study documented a significant reduction in stroke and MI when pioglitazone instead of placebo was given to nondiabetic patients presenting with both stroke/transient ischemic attack and insulin resistance, confirming results from the PROactive (Prospective Pioglitazone Clinical Trial in Macrovascular Events) study in patients with T2DM. Based on these new data, we suggest that the addition of both empagliflozin and pioglitazone to metformin might be the relative best option to reduce the high CV morbidity and mortality of patients with T2DM and already established CV complications. The very recent announcement that the CV outcome study with liraglutide (LEADER) also demonstrated a significant reduction of the composite endpoint (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) gives new hope for further beneficial treatment options for T2DM patients with established CVD.

  2. Treatment of Hypogonadism: Current and Future Therapies

    PubMed Central

    Thirumalai, Arthi; Berkseth, Kathryn E.; Amory, John K.

    2017-01-01

    The treatment of hypogonadism in men is of great interest to both patients and providers. There are a number of testosterone formulations currently available and several additional formulations under development. In addition, there are some lesser-used alternative therapies for the management of male hypogonadism, which may have advantages for certain patient groups. The future of hypogonadism therapy may lie in the development of selective androgen receptor modulators that allow the benefits of androgens whilst minimizing unwanted side effects. PMID:28149506

  3. Future prospects for anti-cytokine treatment

    PubMed Central

    Feldmann, M.; Miotla, J.; Paleolog, E.; Williams, R.; Malfait, A.; Taylor, P.; Brennan, F.; Maini, R.

    2000-01-01

    The era of anti-cytokine treatment in rheumatology has just begun. The first generation therapeutic agents, biological agents that block tumour necrosis factor α such as monoclonal antibodies or receptor Ig fusion proteins are safe and effective, and so this has generated much interest in how to increase the benefit or deliver it more cost effectively. This article provides a personal view of the coming trends in anti-cytokine treatment. Which of these will be realised in the future will be of interest.

 PMID:11053102

  4. Integrative tobacco cessation: A survey assessing past quit strategies and future interest

    PubMed Central

    Howerter, Amy; Floden, Lysbeth; Matthews, Eva; Muramoto, Myra L.

    2015-01-01

    Purpose Tobacco cessation remains a public health priority. Unassisted quits are most common despite evidence for a combination of guideline-recommended strategies. This paper reports findings from a pilot study designed to assess past quit strategies and tobacco users’ receptiveness to using an integrative clinic that offers both conventional and alternative treatments for future cessation attempts. Methods Participants were recruited from a pool of individuals reporting for jury duty. Paper-pencil surveys assessed smoking, past cessation behaviors, and interest in use of the integrative clinic which offers both conventional and alternative treatments. Current and former smokers (n=304) returned surveys. Results Using multivariate logistic regression, past physiological quit strategies, past behavioral quit strategies, and use of multiple quit strategies increased agreement with interest in future use of an integrative clinic option. Additionally, there is support for the notion that if such a clinic were offered, smokers may be inclined to use this resource for a future quit attempt. Conclusions An integrative clinic option for tobacco cessation may encourage smokers to try to quit, especially for those who have used varied cessation strategies in the past. Motivating smokers to use a combined approach for tobacco cessation is a potential future direction for tobacco cessation treatment. Developing and testing an integrative approach may support this effort. PMID:27747150

  5. Age-related macular degeneration: current treatment and future options.

    PubMed

    Moutray, Tanya; Chakravarthy, Usha

    2011-09-01

    Age-related macular degeneration is the leading cause of visual impairment among older adults in the developed world. Epidemiological studies have revealed a number of genetic, ocular and environmental risk factors for this condition, which can be addressed by disease reduction strategies. We discuss the various treatment options for dry and exudative age-related macular degeneration available and explain how the recommended treatment depends on the exact type, location and extent of the degeneration. Currently, vascular endothelial growth factor (VEGF) inhibition therapy is the best available treatment for exudative age-related macular degeneration but is limited by the need for repeated intravitreal injections. The current treatment regime is being refined through research on optimal treatment frequency and duration and type of anti-VEGF drug. Different modes of drug delivery are being developed and in the future other methods of VEGF inhibition may be used.

  6. Optimal Management of Metastatic Melanoma: Current Strategies and Future Directions

    PubMed Central

    Batus, Marta; Waheed, Salman; Ruby, Carl; Petersen, Lindsay; Bines, Steven D.; Kaufman, Howard L.

    2013-01-01

    Melanoma is increasing in incidence and remains a major public health threat. Although the disease may be curable when identified early, advanced melanoma is characterized by widespread metastatic disease and a median survival of less than 10 months. In recent years, however, major advances in our understanding of the molecular nature of melanoma and the interaction of melanoma cells with the immune system have resulted in several new therapeutic strategies that are showing significant clinical benefit. Current therapeutic approaches include surgical resection of metastatic disease, chemotherapy, immunotherapy, and targeted therapy. Dacarbazine, interleukin-2, ipilimumab, and vemurafenib are now approved for the treatment of advanced melanoma. In addition, new combination chemotherapy regimens, monoclonal antibodies blocking the programmed death-1 (PD-1)/PD-ligand 1 pathway, and targeted therapy against CKIT, mitogen-activated protein/extracellular signal-regulated kinase (MEK), and other putative signaling pathways in melanoma are beginning to show promise in early-phase clinical trials. Further research on these modalities alone and in combination will likely be the focus of future clinical investigation and may impact the outcomes for patients with advanced melanoma. PMID:23677693

  7. University Continuing Education: Strategies for an Uncertain Future.

    ERIC Educational Resources Information Center

    Baskett, H. K.; Hamilton, A. Bruce

    Some of the most common predictions relating to university continuing education units provide a base from which a discussion of future strategies can begin. These include the following: the Big Generation (i.e., baby boomers) is here; knowledge, not products, is the major focus of society; competition for the traditional university continuing…

  8. University Continuing Education: Strategies for an Uncertain Future.

    ERIC Educational Resources Information Center

    Baskett, H. K.; Hamilton, A. Bruce

    Some of the most common predictions relating to university continuing education units provide a base from which a discussion of future strategies can begin. These include the following: the Big Generation (i.e., baby boomers) is here; knowledge, not products, is the major focus of society; competition for the traditional university continuing…

  9. Treatment strategy of elderly rheumatoid arthritis.

    PubMed

    Takeda, Tsuyoshi

    2016-01-01

      Since the general population is ageing, the number and the mean age of elderly patients of rheumatoid arthritis (RA) have increased. Elderly RA is classified into two clinical subsets, younger onset elderly RA (YORA) and elderly-onset RA (EORA). In the past literature, onset after 60 years of age is mainly adopted as the classical definition of EORA. Elderly-YORA patients, in addition to disease-modifying antirheumatic drugs, sometimes need analgestics, joint surgery and rehabilitation taking into account their bone destruction and their activities of daily living. Early phase EORA patients should be treated using the treat-to-target strategy, although low disease activity is the realistic goal due to their co-morbidities, patient factors and drug-related risks. Methotrexate (MTX) is the anchor drug in the treatment of EORA. It should be started at low dose (2-4 mg/day) and if tolerated, the dosage is carefully increased. In the case of renal dysfunction or dementia, and MTX is intolerable, biologics monotherapy could be a choice of treatment. Tapering of glucocorticoid, as far as possible, is needed because it is one of the risk factors of infection. Treatment of super-aged RA patients is a future agenda.

  10. Soil Contamination and Remediation Strategies. Current research and future challenge

    NASA Astrophysics Data System (ADS)

    Petruzzelli, G.

    2012-04-01

    eliminating the source of pollution, but also on blocking the pathways from contaminants to receptors or reducing the exposure to contaminants,. Future challenge integration of sustainability into remediation decision-making. Soil is not a waste! There is a growing interest in the clean up approaches that maintain soil quality after remediation treatments. This issue is of great importance in the U.S.A. where the EPA from 2009 is promoting innovative clean-up strategies (Green Remediation). Green remediation is defined as the practice of considering all environmental effects of remedy and incorporating options to maximize environmental benefit of cleanup actions . These remediation strategies restore contaminated sites to productive use with a great attention to the global environmental quality, including the preservation of soil functionality according to the following principles: use minimally invasive technologies; use passive energy technologies such as bioremediation and phytoremediation as primary remedies or finishing steps where possible and effective; minimize soil and habitat disturbance; minimize bioavailability of contaminants trough adequate contaminant source and plume control If we move from the current definition of remedial targets based on total concentrations, technologies with low impact on the environment can be utilized reducing the wrong choice to disposal soil in landfill destroying quickly a not renewable essential resource.

  11. Pharmacological treatment of anxiety disorders: Current treatments and future directions✩

    PubMed Central

    Farach, Frank J.; Pruitt, Larry D.; Jun, Janie J.; Jerud, Alissa B.; Zoellner, Lori A.; Roy-Byrne, Peter P.

    2012-01-01

    Modern pharmacological treatments for anxiety disorders are safer and more tolerable than they were 30 years ago. Unfortunately, treatment efficacy and duration have not improved in most cases despite a greater understanding of the pathophysiology of anxiety. Moreover, innovative treatments have not reached the market despite billions of research dollars invested in drug development. In reviewing the literature on current treatments, we argue that evidence-based practice would benefit from better research on the causes of incomplete treatment response as well as the comparative efficacy of drug combinations and sequencing. We also survey two broad approaches to the development of innovative anxiety treatments: the continued development of drugs based on specific neuroreceptors and the pharmacological manipulation of fear-related memory. We highlight directions for future research, as neither of these approaches is ready for routine clinical use. PMID:23023162

  12. Update and future of systemic acne treatment.

    PubMed

    Zouboulis, Christos C; Piquero-Martin, Jaime

    2003-01-01

    Systemic treatment is required in patients with moderate-to-severe acne, especially when acne scars start to occur. Antibiotics with anti-inflammatory properties, such as tetracyclines (oxytetracycline, tetracycline chloride, doxycycline, minocycline and limecycline) and macrolide antibiotics (erythromycin and azithromycin) are the agents of choice for papulopustular acne, even though the emerging resistant bacterial strains are minimizing their effect, especially regarding erythromycin. Systemic antibiotics should be administered during a period of 8-12 weeks. In severe papulopustular and in nodulocystic/conglobate acne, oral isotretinoin is the treatment of choice. Hormonal treatment represents an alternative regimen in female acne, whereas it is mandatory in resistant, severe pubertal or post-adolescent forms of the disease. Compounds with anti-androgenic properties include estrogens combined with progestins, such as ethinyl estradiol with cyproterone acetate, chlormadinone acetate, desogestrel, drospirenone, levonogestrel, norethindrone acetate, norgestimate, and other anti-androgens directly blocking the androgen receptor (flutamide) or inhibiting androgen activity at various levels, corticosteroids, spironolactone, cimetidine, and ketoconazole. After 3 months of treatment control of seborrhea and acne can be obtained. Low-dose corticosteroids (prednisone, prednisolone, or dexamethasone) are indicated in patients with adrenal hyperandrogenism or acne fulminans. New developments and future trends represent low-dose long-term isotretinoin regimens, new isotretinoin formulations (micronized isotretinoin), isotretinoin metabolites, combination treatments to reduce toxicity, insulin-sensitizing agents, 5alpha-reductase type 1 inhibitors, antisense oligonucleotide molecules, and, especially, new anti-inflammatory agents, such as lipoxygenase inhibitors.

  13. [Current and future medical treatment of Alzheimer's disease].

    PubMed

    Lemper, J C

    2005-09-01

    The current treatment of Alzheimer's disease (MA) is based on a symptomatic pharmacological therapy of the cognitive decline and the behavioural disturbances. Progress towards understanding the cellular and molecular alterations responsible for the disease promise therapeutic strategies based upon the pathological processes. Corrections of dysregulations of the brain's neurotransmitters (cholinergic deficit and glutamatergic overstimulation) bring significant but modest therapeutic improvement. The pivotal role of the proteolytic processing of the amyloid precursor protein (APP) in neuronal death suggests pharmacological inhibition of the secretases; amyloid antiaggregant therapies are possible, vaccination against AB wil need new immunisation protocols, Anti-inflammatory drugs and antioxydant agents as calcium channel blockers could help against the neurotoxic cascade of Abeta, some cholesterol-lowering drugs could enhance its clearance. This article reviews the available data on current pharmacological treatments, and the future possible strategies that could modify the evolution, or prevent Alzheimer's disease.

  14. Allergy immunotherapy: the future of allergy treatment.

    PubMed

    Larsen, Jørgen Nedergaard; Broge, Louise; Jacobi, Henrik

    2016-01-01

    Allergic respiratory disease represents a significant and expanding health problem worldwide. Allergic symptoms, such as asthma and hay fever, cause sleep impairment and reduce school and work performance. The cost to society is substantial. Allergen avoidance and pharmacotherapy cannot control the disease. Only allergy immunotherapy has disease-modifying potential and should be included in optimal treatment strategies. Allergy immunotherapy was first administered as subcutaneous injections and has been practiced for the past 100 years or so. Recently, tablet-based sublingual allergy immunotherapy (SLIT) was introduced with comprehensive clinical documentation. SLIT tablets represent a more patient-friendly concept because they can be used for self-treatment at home. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Achondroplasia: pathogenesis and implications for future treatment.

    PubMed

    Laederich, Melanie B; Horton, William A

    2010-08-01

    Although the genetic defect underlying achondroplasia has been known for over a decade, no effective therapies to stimulate bone growth have emerged. Here we review the recent literature and summarize the molecular mechanisms underlying disease pathology and examine their potential as therapeutic targets. Currently used preclinical models are discussed in the context of recent advances with a special focus on C-type natriuretic peptide. Research on the mutation in Fibroblast Growth Factor Receptor 3 (FGFR3) that causes achondroplasia suggests that disease results from increased signal transduction from the mutant receptor. Thus, current therapeutic strategies have focused on reducing signals emanating from FGFR3. First-generation therapies directly targeting FGFR3, such as kinase inhibitors and neutralizing antibodies, designed for targeting FGFR3 in cancer, are still in the preclinical phase and have yet to translate into the management of achondroplasia. Counteracting signal transduction pathways downstream of FGFR3 holds promise with the discovery that administration of C-type natriuretic peptide to achondroplastic mice ameliorates their clinical phenotype. However, more research into long-term effectiveness and safety of this strategy is needed. Direct targeting of therapeutic agents to growth plate cartilage may enhance efficacy and minimize side effects of these and future therapies. Current research into the pathogenesis of achondroplasia has expanded our understanding of the mechanisms of FGFR3-induced disease and has increased the number of approaches that we may use to potentially correct it. Further research is needed to validate these approaches in preclinical models of achondroplasia.

  16. Current and future treatments for hepatocellular carcinoma.

    PubMed

    Schlachterman, Alexander; Craft, Willie W; Hilgenfeldt, Eric; Mitra, Avir; Cabrera, Roniel

    2015-07-28

    Hepatocellular carcinoma (HCC) represents a unique challenge for physicians and patients. There is no definitively curative treatment. Rather, many treatment and management modalities exist with differing advantages and disadvantages. Both current guidelines and individual patient concerns must be taken into account in order to properly manage HCC. In addition, quality of life issues are particularly complex in patients with HCC and these concerns must also be factored into treatment strategies. Thus, considering all the options and their various pros and cons can quickly become complex for both clinicians and patients. In this review, we systematically discuss the current treatment modalities available for HCC, detailing relevant clinical data, risks and rewards and overall outcomes for each approach. Surgical options discussed include resection, transplantation and ablation. We also discuss the radiation modalities: conformal radiotherapy, yttrium 90 microspheres and proton and heavy ion radiotherapy. The biologic agent Sorafenib is discussed as a promising new approach, and recent clinical trials are reviewed. We then detail currently described molecular pathways implicated in the initiation and progression of HCC, and we explore the potential of each pathway as an avenue for drug exploitation. We hope this comprehensive and forward-looking review enables both clinicians and patients to understand various options and thereby make more informed decisions regarding this disease.

  17. Current and future treatments for hepatocellular carcinoma

    PubMed Central

    Schlachterman, Alexander; Craft Jr, Willie W; Hilgenfeldt, Eric; Mitra, Avir; Cabrera, Roniel

    2015-01-01

    Hepatocellular carcinoma (HCC) represents a unique challenge for physicians and patients. There is no definitively curative treatment. Rather, many treatment and management modalities exist with differing advantages and disadvantages. Both current guidelines and individual patient concerns must be taken into account in order to properly manage HCC. In addition, quality of life issues are particularly complex in patients with HCC and these concerns must also be factored into treatment strategies. Thus, considering all the options and their various pros and cons can quickly become complex for both clinicians and patients. In this review, we systematically discuss the current treatment modalities available for HCC, detailing relevant clinical data, risks and rewards and overall outcomes for each approach. Surgical options discussed include resection, transplantation and ablation. We also discuss the radiation modalities: conformal radiotherapy, yttrium 90 microspheres and proton and heavy ion radiotherapy. The biologic agent Sorafenib is discussed as a promising new approach, and recent clinical trials are reviewed. We then detail currently described molecular pathways implicated in the initiation and progression of HCC, and we explore the potential of each pathway as an avenue for drug exploitation. We hope this comprehensive and forward-looking review enables both clinicians and patients to understand various options and thereby make more informed decisions regarding this disease. PMID:26229392

  18. Augmentation strategies for treatment-resistant depression.

    PubMed

    Carvalho, André F; Machado, Juliana Raulino; Cavalcante, João L

    2009-01-01

    The majority of patients with depression fail to remit on one or more antidepressant trials. These patients have treatment-resistant depression (TRD) with high relapsing rates. Augmentation pharmacotherapy refers to the addition of drugs that are not standard antidepressants in order to enhance the effect of a classical antidepressant drug. This review highlights the current status and future research directions of augmentation treatments for TRD with a special focus on research data published within the past year. Atypical antipsychotics, stimulants, pindolol, lithium, lamotrigine and mecamylamine were tested for efficacy in clinical trials. Most of the trials were not controlled or had limited sample size. Recent data now support the use of some atypical antipsychotics to augment depression resistant to the newer, more selective, antidepressants. Lithium and triiodothyronin (T3) augmentation of tricyclic agents remains the best studied strategy. Data converge to demonstrate the efficacy of some atypical antipsychotics as augmenting agents to selective serotonin reuptake inhibitors. Further adequately powered controlled trials on augmentation pharmacotherapy of TRD are necessary.

  19. Fractal Formation and Trend Trading Strategy in Futures Market

    NASA Astrophysics Data System (ADS)

    Masteika, Saulius; Rutkauskas, Aleksandras V.; Lopata, Audrius

    The paper presents the details of trend trading algorithm in futures market. A contribution of this paper lies in a modified chart pattern related to a fractal formation, nonlinearity and chaos theory, broadly discussed by Benoit B. Mandelbrot and Bill M. Williams. As typical fractal pattern often is being applied in conjunction with other forms of technical analysis, like moving averages, Elliott Waves analysis or MACD indicators the proposed pattern is presented as a basic indicator itself. The strategy can be applied as up-trend market forecasting tool. The efficiency of the proposed strategy was tested with the most active North American futures contracts using 10 years historical daily data. Experimental results showed better returns if compared to overall market average-CRB index.

  20. Future strategies in the management of coronary artery disease.

    PubMed

    Schwitter, Jürg

    2006-09-01

    New diagnostic techniques have now become available that will enable us to obtain information on coronary artery disease (CAD), which was not previously possible. This is urgently needed, since changes in CAD management are highly desirable considering that up to 60% of patients die due to an insufficient diagnostic strategy (reactive strategy). In this article, the pathophysiology of CAD and the evidence of current concepts on coronary atherosclerosis are critically reviewed. Consequently, a shift from a 'reactive strategy' of CAD management to an active strategy is proposed in order to detect and treat patients before acute myocardial infarcts occur. Reliability, repeatability, cost-effectiveness and comfort are important features of an optimal test for this active strategy. This perspective gives an overview of current and future tests with respect to these features. The novel tomographic techniques are particularly promising with respect to standardization and reproducibility, which will set the basis for the determination of test performance and, consequently, cost-effectiveness. Assessment of cost-effectiveness is increasingly important, since prevalence of CAD is high and will most likely increase, while resources will remain restricted in most countries. Considering these economic restrictions, this article also proposes new mathematical tools using data from prospective trials and large international registries as an objective means to select the best tests for CAD diagnosis and management, and to identify those patient subsets which benefit most from an active strategy.

  1. Current and future treatment options for gonorrhoea.

    PubMed

    Ison, Catherine A; Deal, Carolyn; Unemo, Magnus

    2013-12-01

    The delivery of effective antimicrobial therapy is essential for public health control of gonorrhoea, in the absence of a suitable vaccine. The antimicrobial agent chosen should have high efficacy and quality, lack toxicity and give >95% success when given empirically. Guidelines, which are informed by surveillance data, are used to aid clinicians in their choice of appropriate agent. Historically, gonorrhoea treatment has been delivered as a single, directly observed dose but this has resulted in failure of successive antimicrobial agents which have been replaced by a new antimicrobial to which resistance has been rare or non-existing. Following the drift towards decreased susceptibility and treatment failure to the extended spectrum cephalosporins, and the lack of 'new' alternative antimicrobials, the threat of difficult to treat or untreatable gonorrhoea has emerged. The challenge of maintaining gonorrhoea as a treatable infection has resulted in national, regional and global response or action plans. This review discusses different approaches to the future treatment of gonorrhoea including; use of ceftriaxone, the injectable cephalosporin at increased dosage; dual antimicrobial therapy; use of drugs developed for other infections and use of older agents, directed by rapid point of care tests, to susceptible infections. Finally, it is considered whether the time is right to readdress the possibility of developing an effective gonococcal vaccine, given the major advances in our understanding of natural infection, molecular pathogenesis and the revolution in molecular biology techniques.

  2. Future vaccination strategies against tuberculosis: thinking outside the box.

    PubMed

    Kaufmann, Stefan H E

    2010-10-29

    With almost a dozen vaccine candidates in clinical trials, tuberculosis (TB) research and development is finally reaping the first fruits of its labors. Vaccine candidates in clinical trials may prevent TB disease reactivation by efficiently containing the pathogen Mycobacterium tuberculosis (Mtb). Future research should target vaccines that achieve sterile eradication of Mtb or even prevent stable infection. These are ambitious goals that can be reached only by highly cooperative engagement of basic immunologists, vaccinologists, and clinical researchers--or in other words, by translation from basic immunology to vaccine research and development, as well as reverse translation of insights from clinical trials back to hypothesis-driven research in the basic laboratory. Here, we review current and future strategies toward the rational design of novel vaccines against TB, as well as the progress made thus far, and the hurdles that need to be overcome in the near and distant future. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Lactic Acidosis: Current Treatments and Future Directions.

    PubMed

    Kraut, Jeffrey A; Madias, Nicolaos E

    2016-09-01

    Mortality rates associated with severe lactic acidosis (blood pH<7.2) due to sepsis or low-flow states are high. Eliminating the triggering conditions remains the most effective therapy. Although recommended by some, administration of sodium bicarbonate does not improve cardiovascular function or reduce mortality. This failure has been attributed to both reduction in serum calcium concentration and generation of excess carbon dioxide with intracellular acidification. In animal studies, hyperventilation and infusion of calcium during sodium bicarbonate administration improves cardiovascular function, suggesting that this approach could allow expression of the positive aspects of sodium bicarbonate. Other buffers, such as THAM or Carbicarb, or dialysis might also provide base with fewer untoward effects. Examination of these therapies in humans is warranted. The cellular injury associated with lactic acidosis is partly due to activation of NHE1, a cell-membrane Na(+)/H(+) exchanger. In animal studies, selective NHE1 inhibitors improve cardiovascular function, ameliorate lactic acidosis, and reduce mortality, supporting future research into their possible use in humans. Two main mechanisms contribute to lactic acid accumulation in sepsis and low-flow states: tissue hypoxia and epinephrine-induced stimulation of aerobic glycolysis. Targeting these mechanisms could allow for more specific therapy. This Acid-Base and Electrolyte Teaching Case presents a patient with acute lactic acidosis and describes current and future approaches to treatment. Published by Elsevier Inc.

  4. Viral encephalitis: current treatments and future perspectives.

    PubMed

    Domingues, Renan Barros

    2012-12-01

    Several viruses may cause central nervous system infections that lead to a broad range of clinical manifestations. The course of the viral encephalitis can be acute, sub acute, or chronic. Some viruses have the ability to enter into the brain and cause direct injury, while others activate inflammatory cells that attack the central nervous system (CNS) secondarily. Some types of viral encephalitis occur in previously healthy individuals, while others affect immunocompromised patients. The epidemiology of viral encephalitis has undergone changes in recent years. Factors such as evolving lifestyles and ecological changes have had a considerable impact on the epidemiology of some types of viral encephalitis. The result is a change in the etiology spectrum of viral encephalitis, with new types of encephalitis arising or returning from time to time. Many scientific achievements in neuroimaging, molecular diagnosis, antiviral therapy, immunomodulatory treatments, and neurointensive care have allowed more precise and earlier diagnoses and more efficient treatments, resulting in improved outcomes. Despite these advances, there is still considerable morbidity and mortality related to these disorders. This aim of this article is to review the current knowledge of the current drugs used in the management of the most important viral encephalitis, focusing on the mechanisms of action, efficacy, and side effects of the drugs. In addition, future perspectives in this area will be addressed. Despite the technological advances, much effort has yet to be undertaken to reduce the impact of these potentially devastating diseases.

  5. Overactive bladder syndrome pharmacotherapy: future treatment options

    PubMed Central

    2015-01-01

    Overactive bladder syndrome (OAB) is a lifestyle disease and its incidence increases with age. Although it is not a life-threatening disease, it is known to have a significant impact on the quality of life. The first-choice pharmacological treatment of OAB is antimuscarinics. However, their limited clinical effectiveness and unsatisfactory tolerance profile, combined with the advancement of knowledge on the aetiopathogenesis of the disease, have inspired research on new pharmacotherapy options for OAB. Basic research has provided foundations for the development of new OAB treatments, which seem very promising and can be applied in clinical practice. The mechanisms of the studied compounds are based on their effect on certain receptors and neurotransmitters that contribute to regulating the micturition reflex. These compounds are not only more receptor-specific as compared to currently used drugs, but also some of them are organ-specific. Some of such compounds have already passed the proof-of-concept stage of development and have the therapeutic potential to determine the future of OAB pharmacotherapy. This review focuses on the mechanisms of substances that are now undergoing pre-clinical and clinical tests and their effects on the micturition cycle, while also identifying opportunities for using them with specific groups of patients. Due to the fact that OAB is a disease of symptoms and its aetiopathogenesis is complex, it seems that modern treatment methods should be tailor-made and based on the pathophysiological mechanisms that induce disease symptoms, rather than only treating the symptoms by inhibiting the contractility of the urinary bladder. PMID:26848291

  6. Current Status and Future Prospects for Esophageal Cancer Treatment

    PubMed Central

    Kuwano, Hiroyuki

    2016-01-01

    The local control effect of esophagectomy with three-field lymph node dissection (3FLD) is reaching its limit pending technical advancement. Minimally invasive esophagectomy (MIE) by thoracotomy is slowly gaining acceptance due to advantages in short-term outcomes. Although the evidence is slowly increasing, MIE is still controversial. Also, the results of treatment by surgery alone are limiting, and multimodality therapy, which includes surgical and non-surgical treatment options including chemotherapy, radiotherapy, and endoscopic treatment, has become the mainstream therapy. Esophagectomy after neoadjuvant chemotherapy (NAC) is the standard treatment for clinical stages II/III (except for T4) esophageal cancer, whereas chemoradiotherapy (CRT) is regarded as the standard treatment for patients who wish to preserve their esophagus, those who refuse surgery, and those with inoperable disease. CRT is also usually selected for clinical stage IV esophageal cancer. On the other hand, with the spread of CRT, salvage esophagectomy has traditionally been recognized as a feasible option; however, many clinicians oppose the use of surgery due to the associated unfavorable morbidity and mortality profile. In the future, the improvement of each treatment result and the establishment of individual strategies are important although esophageal cancer has many treatment options. PMID:28003586

  7. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy.

    PubMed

    Khalil, Danny N; Smith, Eric L; Brentjens, Renier J; Wolchok, Jedd D

    2016-05-01

    In the past decade, advances in the use of monoclonal antibodies (mAbs) and adoptive cellular therapy to treat cancer by modulating the immune response have led to unprecedented responses in patients with advanced-stage tumours that would otherwise have been fatal. To date, three immune-checkpoint-blocking mAbs have been approved in the USA for the treatment of patients with several types of cancer, and more patients will benefit from immunomodulatory mAb therapy in the months and years ahead. Concurrently, the adoptive transfer of genetically modified lymphocytes to treat patients with haematological malignancies has yielded dramatic results, and we anticipate that this approach will rapidly become the standard of care for an increasing number of patients. In this Review, we highlight the latest advances in immunotherapy and discuss the role that it will have in the future of cancer treatment, including settings for which testing combination strategies and 'armoured' CAR T cells are recommended.

  8. [Treatments strategies for intracranial cavernomas].

    PubMed

    Stienen, Martin N; Bijlenga, Philippe; Schaller, Karl; Hildebrandt, Gerhard; Gautschi, Oliver P

    2014-11-26

    Cerebral cavernomatous malformations (CCM) are a subgroup of low-pressure cerebral vascular malformation. They have an estimated prevalence of 0,1-4% of the population and account for 8-15% of all cerebral vascular malformations. Depending on their size and localization (supratentorial or infratentorial, brain stem), CCM may present with focal bleedings with or without neurological deficits, as epileptic seizures, or are diagnosed incidentally by MRI performed for unspecific symptoms (e.g. headache, vertigo), especially in younger patients (mostly in 2nd or 3rd decade). The decision-making in patients with CCM can be classified into four categories: surgical or conservative treatment of symptomatic or incidental lesions. The decision regarding the optimal therapy in the individual patient must be made in the knowledge of the natural history (risk for bleeding or epilepsy) on the one hand, and the surgical possibilities (accessibility of the lesion) including their estimated outcome on the other hand. Therefore, careful patient selection and appropriate experience of the centre is warranted in the management of CCM.

  9. Future directions in the treatment of osteosarcoma.

    PubMed

    Bishop, Michael W; Janeway, Katherine A; Gorlick, Richard

    2016-02-01

    Overall survival rates for osteosarcoma have remained essentially unchanged over the past 3 decades despite attempts to improve outcome via dose intensification and modification based on response. This review describes recent findings from contemporary clinical trials, advances in the comprehension of osteosarcoma biology and genomic complexity, and potential opportunities using targeted and immune-mediated therapies. Recent results from international collaborative trials have failed to demonstrate an ability to improve outcomes using a design in which the randomized question is dictated based on histologic response to preoperative chemotherapy. Novel prognostic markers assessable at diagnosis are vital to identifying subsets of osteosarcoma. Clinical trials focus has now shifted to serial phase II studies of novel agents to evaluate for activity in recurrent and refractory disease. In-depth analyses have revealed profound genomic instability and heterogeneity across patients, with nearly universal TP53 aberration. Although driver mutational events have not clearly been established, frequent derangements in specific pathways may suggest opportunities for therapeutic exploitation. Genomic complexity may lend support to a role for immune-mediated therapies. Rigorous preclinical investigations are potentially generating novel strategies for the treatment of osteosarcoma that will inform the next generation of clinical trials, with the opportunity to identify agents that will improve survival outcomes.

  10. Future Directions in the Treatment of Osteosarcoma

    PubMed Central

    Bishop, Michael W.; Janeway, Katherine A.; Gorlick, Richard

    2016-01-01

    Purpose of Review Overall survival rates for osteosarcoma have remained essentially unchanged over the past three decades despite attempts to improve outcome via dose intensification and modification based on response. This review describes recent findings from contemporary clinical trials, advances in comprehension of osteosarcoma biology and genomic complexity, and potential opportunities using targeted and immune-mediated therapies. Recent Findings Recent results from international collaborative trials have failed to demonstrate an ability to improve outcomes using a design in which the randomized question is dictated based on histologic response to preoperative chemotherapy. Novel prognostic markers assessable at diagnosis are vital to identifying subsets of osteosarcoma. Clinical trials focus has now shifted to serial phase II studies of novel agents to evaluate for activity in recurrent and refractory disease. In-depth analyses have revealed profound genomic instability and heterogeneity across patients, with nearly universal TP53 aberration. While driver mutational events have not clearly been established, frequent derangements in specific pathways may suggest opportunities for therapeutic exploitation. Genomic complexity may lend support to a role for immune-mediated therapies. Summary Rigorous preclinical investigations are potentially generating novel strategies for treatment of osteosarcoma that will inform the next generation of clinical trials, with the opportunity to identify agents that will improve survival outcomes. PMID:26626558

  11. Treatment of hemophilia in the near future.

    PubMed

    Peyvandi, Flora; Garagiola, Isabella

    2015-11-01

    Advancements and debacles have characterized hemophilia treatment over the past 50 years. The 1970s saw the availability of plasma-derived concentrates making prophylaxis and home therapy possible. This optimistic perception changed extremely in the early 1980s, when most people with hemophilia were infected with HIV and hepatitis viruses. Then, also in the 1980s, the rapid progress in molecular biology led to the development of recombinant therapeutic products. This important advancement was a huge technological leap fresh off from the earlier 1980s disaster. Now in the 21st century, the newer bioengineering drugs open a new hopeful phase for the management of hemophilia. The current efforts are concentrated on producing novel coagulation factors with prolonged bioavailability, increased potency, and resistance to inactivation and potentially reduced immunogenicity; this phase of evolution is improving very quickly. 2014 is the year of marketing approval by the Food and Drug Administration of the first bioengineered FVIII and FIX long-acting drugs, using Fc-fusion strategy. This represents the first significant advance in the hemophilia therapy that dramatically transforms patient management by substantially reducing the frequency of injections, improving compliance, and simplifying prophylaxis and, in turn, refining the quality of life of hemophilia patients, offering them a nearly normal life expectancy, particularly to newborns with hemophilia B.

  12. Antibiotic resistance: how it arises, the current position and strategies for the future.

    PubMed

    Perry, Christine; Hall, Carly

    After 70 years of antibiotic therapy, the threat of untreatable infections is again a reality with resistance to antibiotics increasing in both Gram positive and Gram negative bacteria. Antibiotic-resistant bacteria cause both community and healthcare associated infections, presenting challenges in treatment and management. The development of new and novel antibiotics, particularly for Gram negative bacteria, is worryingly lacking. This article reviews the current situation and examines future strategies to tackle the continued threat of bacterial resistance.

  13. [Cardiogenic shock: treatment of the near future].

    PubMed

    Gaxiola, Efraín; Ramírez-Sánchez, Ulises

    2006-01-01

    The mortality rate for cardiogenic shock has decreased over the past decade. These improvements are presumed to reflect increased use of intraaortic ballon counterpulsation and coronary reperfusion strategies which, by restoring patency to the infarct-related artery, can limit infarct size. Despite these therapeutic measures, mortality rates remain elevated. Current strategies are aimed at decreasing reperfusion times and measures to preserve and prolong myocardial cell viability.

  14. Adaptive Treatment Strategies in Chronic Disease

    PubMed Central

    Lavori, Philip W.; Dawson, Ree

    2009-01-01

    An adaptive treatment strategy (ATS) is a rule for adapting a treatment plan to a patient’s history of previous treatments and the response to those treatments. The ongoing management of chronic disease defines an ATS, which may be implicit and hidden, or explicit and well-specified. The ATS is characterized by the use of intermediate, early markers of response to dynamically alter treatment decisions, in order to achieve a favorable ultimate outcome. We illustrate the concept of ATS with some examples and describe the way that the effect of initial treatment decisions depends on the performance of subsequent decisions at later stages. We show how to compare two or more ATS, or to determine an optimal ATS, using a sequential multiple assignment randomized (SMAR) trial. We observe that clinical trials designers might find the ATS concept useful in improving the efficiency and ecological relevance of clinical trials. PMID:17914924

  15. Stereotactic body radiotherapy: current strategies and future development

    PubMed Central

    2016-01-01

    Stereotactic body radiotherapy (SBRT) has emerged as the standard treatment for medically inoperable early-staged non-small cell lung cancer (NSCLC). The local control rate after SBRT is over 90%. Some forms of tumour motion management and image-guided radiation delivery techniques are the prerequisites for fulfilment of its goal to deliver a high radiation dose to the tumour target without overdosing surrounding normal tissues. In this review, the current strategies of tumour motion management will be discussed, followed by an overview of various image-guided radiotherapy (RT) systems and devices available for clinical practice. Besides medically inoperable stage I NSCLC, SBRT has also been widely adopted for treatment of oligometastasis involving the lungs. Its possible applications in various other cancer illnesses are under extensive exploration. The progress of SBRT is critically technology-dependent. With advancement of technology, the ideal of personalised, effective and yet safe SBRT is already on the horizon. PMID:27606082

  16. Present and Future: Pharmacologic Treatment of Obesity

    PubMed Central

    Glandt, Mariela; Raz, Itamar

    2011-01-01

    Obesity now presents one of the biggest health problems of our times. Diet and exercise are best for both prevention and treatment; unfortunately, both require much discipline and are difficult to maintain. Medications offer a possible adjunct, but their effect is modest, they are limited by side effects, and the weight loss lasts only as long as the drug is being taken, since as soon as treatment is stopped, the weight is regained. Sibutramine, a sympathomimetic medication which was available for long-term treatment, is the most recent of the drugs to be withdrawn from the market due to side effects; in this case it was an increased risk of cardiovascular events. This paper reviews those medications which are available for treatment of obesity, including many of those recently taken off the market. It also discusses some of the newer treatments that are currently being investigated. PMID:21331293

  17. Preparing Future Geoscience Professionals: Needs, Strategies, Programs, and Online Resources

    NASA Astrophysics Data System (ADS)

    Macdonald, H.; Manduca, C. A.; Ormand, C. J.; Dunbar, R. W.; Beane, R. J.; Bruckner, M.; Bralower, T. J.; Feiss, P. G.; Tewksbury, B. J.; Wiese, K.

    2011-12-01

    Geoscience faculty, departments, and programs play an important role in preparing future geoscience professionals. One challenge is supporting the diversity of student goals for future employment and the needs of a wide range of potential employers. Students in geoscience degree programs pursue careers in traditional geoscience industries; in geoscience education and research (including K-12 teaching); and opportunities at the intersection of geoscience and other fields (e.g., policy, law, business). The Building Strong Geoscience Departments project has documented a range of approaches that departments use to support the development of geoscience majors as professionals (serc.carleton.edu/departments). On the Cutting Edge, a professional development program, supports graduate students and post-doctoral fellows interested in pursuing an academic career through workshops, webinars, and online resources (serc.carleton.edu/NAGTWorkshops/careerprep). Geoscience departments work at the intersection of student interests and employer needs. Commonly cited program goals that align with employer needs include mastery of geoscience content; field experience; skill in problem solving, quantitative reasoning, communication, and collaboration; and the ability to learn independently and take a project from start to finish. Departments and faculty can address workforce issues by 1) implementing of degree programs that develop the knowledge, skills, and attitudes that students need, while recognizing that students have a diversity of career goals; 2) introducing career options to majors and potential majors and encouraging exploration of options; 3) advising students on how to prepare for specific career paths; 4) helping students develop into professionals, and 5) supporting students in the job search. It is valuable to build connections with geoscience employers, work with alumni and foster connections between students and alumni with similar career interests, collaborate with

  18. Kawasaki disease: etiopathogenesis and novel treatment strategies.

    PubMed

    Agarwal, Shreya; Agrawal, Devendra K

    2017-03-01

    Kawasaki disease is an acute febrile systemic vasculitis that predominantly occurs in children below five years of age. Its etiopathogenesis is still not clear, but it is thought to be a complex interplay of genetic factors, infections and immunity. Areas covered: This review article discusses in detail Kawasaki disease, with particular emphasis on the recent updates on its pathogenesis and upcoming alternate treatment options. Though self-limiting in many cases, it can lead to severe complications like coronary artery aneurysms and thrombo-embolic occlusions, and hence requires early diagnosis and urgent attention to avoid them. Intravenous immunoglobulin (IVIG) with or without aspirin has remained the sole treatment option for these cases, but 10-15% cases develop resistance to this treatment. Expert commentary: There is a need to develop additional treatment strategies for children with Kawasaki disease. Targeting different steps of pathogenesis could provide us with alternate therapeutic options.

  19. Narcolepsy: current treatment options and future approaches.

    PubMed

    Billiard, Michel

    2008-06-01

    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.

  20. Bone regenerative medicine: classic options, novel strategies, and future directions

    PubMed Central

    2014-01-01

    This review analyzes the literature of bone grafts and introduces tissue engineering as a strategy in this field of orthopedic surgery. We evaluated articles concerning bone grafts; analyzed characteristics, advantages, and limitations of the grafts; and provided explanations about bone-tissue engineering technologies. Many bone grafting materials are available to enhance bone healing and regeneration, from bone autografts to graft substitutes; they can be used alone or in combination. Autografts are the gold standard for this purpose, since they provide osteogenic cells, osteoinductive growth factors, and an osteoconductive scaffold, all essential for new bone growth. Autografts carry the limitations of morbidity at the harvesting site and limited availability. Allografts and xenografts carry the risk of disease transmission and rejection. Tissue engineering is a new and developing option that had been introduced to reduce limitations of bone grafts and improve the healing processes of the bone fractures and defects. The combined use of scaffolds, healing promoting factors, together with gene therapy, and, more recently, three-dimensional printing of tissue-engineered constructs may open new insights in the near future. PMID:24628910

  1. [Treatment of Alzheimer's disease and future approaches].

    PubMed

    Forette, Françoise; Hauw, Jean-Jacques

    2010-01-01

    The progressive neuronal loss in Alzheimer's disease leads to neurochemical abnormalities which provide the basis for symptomatic treatments. Four cholinesterase inhibitors were released in this indication. Meta-analyses have confirmed a beneficial effect on cognitive functioning and activities of daily living. The NMDA receptor antagonist, memantine, was also approved for the treatment of moderate to severe and may be associated. Progress in the patho-physiology of the disease offers some hope of new treatments acting on the cerebral lesions. The amyloid hypothesis allowed the emergence of active or passive immunotherapies, and of secretase inhibitors or modulators. Recent studies have targeted the P tau protein. The brain plasticity and the uses of stem cells offer more distant hope.

  2. Hepatitis C Treatment: current and future perspectives

    PubMed Central

    2010-01-01

    Hepatitis C virus (HCV) is a member of Flaviviridae family and one of the major causes of liver disease. There are about 175 million HCV infected patients worldwide that constitute 3% of world's population. The main route of HCV transmission is parental however 90% intravenous drug users are at highest risk. Standard interferon and ribavirin remained a gold standard of chronic HCV treatment having 38-43% sustained virological response rates. Currently the standard therapy for HCV is pegylated interferon (PEG-INF) with ribavirin. This therapy achieves 50% sustained virological response (SVR) for genotype 1 and 80% for genotype 2 & 3. As pegylated interferon is expensive, standard interferon is still the main therapy for HCV treatment in under developed countries. On the other hand, studies showed that pegylated IFN and RBV therapy has severe side effects like hematological complications. Herbal medicines (laccase, proanthocyandin, Rhodiola kirilowii) are also being in use as a natural and alternative way for treatment of HCV but there is not a single significant report documented yet. Best SVR indicators are genotype 3 and 2, < 0.2 million IU/mL pretreatment viral load, rapid virological response (RVR) rate and age <40 years. New therapeutic approaches are under study like interferon related systems, modified forms of ribavirin, internal ribosome entry site (HCV IRES) inhibitors, NS3 and NS5a inhibitors, novel immunomodulators and specifically targeted anti-viral therapy for hepatitis C compounds. More remedial therapies include caspase inhibitors, anti-fibrotic agents, antibody treatment and vaccines. PMID:21040548

  3. [Pituitary disease: which treatment in the future?].

    PubMed

    Briet, C; Chanson, P

    2011-10-01

    Even if major progress has been made in the medical treatment for pituitary adenomas in the last decades, currently available drugs do not always control hormonal secretion of these tumors. New molecules or new formulations of old drugs are under development. Pituitary stem cells research is currently also very active. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  4. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy

    PubMed Central

    Khalil, Danny N.; Smith, Eric L.; Brentjens, Renier J.; Wolchok, Jedd D.

    2017-01-01

    In the past decade, advances in the use of monoclonal antibodies (mAbs) and adoptive cellular therapy to treat cancer by modulating the immune response have led to unprecedented responses in patients with advanced-stage tumours that would otherwise have been fatal. To date, three immune-checkpoint-blocking mAbs have been approved in the USA for the treatment of patients with several types of cancer, and more patients will benefit from immunomodulatory mAb therapy in the months and years ahead. Concurrently, the adoptive transfer of genetically modified lymphocytes to treat patients with haematological malignancies has yielded dramatic results, and we anticipate that this approach will rapidly become the standard of care for an increasing number of patients. In this Review, we highlight the latest advances in immunotherapy and discuss the role that it will have in the future of cancer treatment, including settings for which testing combination strategies and ‘armoured’ CAR T cells are recommended. PMID:26977780

  5. Entry inhibitors and future treatment of hepatitis C.

    PubMed

    Fofana, Isabel; Jilg, Nikolaus; Chung, Raymond T; Baumert, Thomas F

    2014-04-01

    Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. Furthermore, HCV-induced liver disease is the leading indication for liver transplantation. The recent introduction of direct-acting antivirals (DAAs) has revolutionized HCV treatment by making possible the cure of the majority of patients. However, their efficacy and safety in difficult-to-treat patients such as patients receiving immunosuppression, those with advanced liver disease, co-morbidity and HIV/HCV-co-infection remain to be determined. Furthermore, prevention of liver graft infection remains a pressing issue. HCV entry inhibitors target the very first step of the HCV life cycle and efficiently inhibit cell-cell transmission - a key prerequisite for viral spread. Because of their unique mechanism of action on cell-cell transmission they may provide a promising and simple perspective for prevention of liver graft infection. A high genetic barrier to resistance and complementary mechanism of action compared to DAAs makes entry inhibitors attractive as a new strategy for treatment of multi-resistant or difficult-to-treat patients. Clinical studies are needed to determine the future role of entry inhibitors in the arsenal of antivirals to combat HCV infection. This article forms part of a symposium in Antiviral Research on "Hepatitis C: next steps toward global eradication." Copyright © 2014. Published by Elsevier B.V.

  6. Polyphenols: Potential Future Arsenals in the Treatment of Diabetes.

    PubMed

    Solayman, Md; Ali, Yousuf; Alam, Fahmida; Islam, Md Asiful; Alam, Nadia; Khalil, Md Ibrahim; Gan, Siew Hua

    2016-01-01

    Diabetes mellitus (DM) is one of the most common endocrine metabolic disorders. In addition to exercise and diet, oral anti-diabetic drugs have been used as a part of the management strategy worldwide. Unfortunately, none of the conventional anti-diabetic drugs are without side effects, and these drugs pose an economic burden. Therefore, the investigation of novel anti-diabetic regimens is a major challenge for researchers, in which nature has been the primary resource for the discovery of potential therapeutics. Many plants have been shown to act as anti-diabetic agents, in which the main active constituents are believed to be polyphenols. Natural products containing high polyphenol levels can control carbohydrate metabolism by various mechanisms, such as protecting and restoring beta-cell integrity, enhancing insulin releasing activity, and increasing cellular glucose uptake. Blackberries, red grapes, apricots, eggplant and popular drinks such as coffee, cocoa and green tea are all rich in polyphenols, which may dampen insulin resistance and be natural alternatives in the treatment of diabetes. Therefore, the aim of this review is to report on the available anti-diabetic polyphenols (medicinal plants, fruits and vegetables), their mechanisms in the various pathways of DM and their correlations with DM. Additionally, this review emphasizes the types of polyphenols that could be potential future resources in the treatment of DM via either novel regimens or as supplementary agents.

  7. Treatment of hepatocellular carcinoma: present and future.

    PubMed

    Genco, Chiara; Cabibbo, Giuseppe; Maida, Marcello; Brancatelli, Giuseppe; Galia, Massimo; Alessi, Nicola; Butera, Giuseppe; Genova, Claudio; Romano, Piero; Raineri, Maurizio; Giarratano, Antonello; Midiri, Massimo; Cammà, Calogero

    2013-04-01

    Hepatocellular carcinoma is a major health problem. It is the sixth most common cancer worldwide and the third most common cause of cancer-related death. Despite the availability of several treatment opportunities, diagnosis is still made in an advanced phase, limiting application of most therapeutic choices that currently are based on the Barcelona Clinic Cancer Liver Classification and include surgical resection, orthotopic liver transplantation and ablative methods for very early and early disease, arterial chemoembolization for intermediate stages and systemic therapy with sorafenib for advanced hepatocellular carcinoma. Thanks to novel advancements in knowledge of molecular pathogenesis of this tumor, many new systemic agents and locoregional treatments are in different stages of clinical development and they represent an important promise of further improvements in patients' survival.

  8. Future pharmacological treatments for substance use disorders.

    PubMed

    Forray, Ariadna; Sofuoglu, Mehmet

    2014-02-01

    Substance use disorders represent a serious public health and social issue worldwide. Recent advances in our understanding of the neurobiological basis of the addictive processes have led to the development of a growing number of pharmacological agents to treat addictions. Despite this progress, there are no approved pharmacological treatments for cocaine, methamphetamine and cannabis addiction. Moving treatment development to the next stage will require novel ways of approaching substance use disorders. One such novel approach is to target individual vulnerabilities, such as cognitive function, sex differences and psychiatric comorbidities. This review provides a summary of promising pharmacotherapies for alcohol, opiate, stimulant and nicotine addictions. Many medications that target positive and negative reinforcement of drugs, as well as individual vulnerabilities to addiction, are in different phases of development. Clinical trials testing the efficacy of these medications for substance use disorder are warranted. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  9. Gut hormones: the future of obesity treatment?

    PubMed Central

    McGavigan, Anne K; Murphy, Kevin G

    2012-01-01

    Obesity is a major worldwide health problem. The treatment options are severely limited. The development of novel anti-obesity drugs is fraught with efficacy and safety issues. Consequently, several investigational anti-obesity drugs have failed to gain marketing approval in recent years. Anorectic gut hormones offer a potentially safe and viable option for the treatment of obesity. The prospective utility of gut hormones has improved drastically in recent years with the development of longer acting analogues. Additionally, specific combinations of gut hormones have been demonstrated to have additive anorectic effects. This article reviews the current stage of anti-obesity drugs in development, focusing on gut hormone-based therapies. PMID:22452339

  10. Gut hormones: the future of obesity treatment?

    PubMed

    McGavigan, Anne K; Murphy, Kevin G

    2012-12-01

    Obesity is a major worldwide health problem. The treatment options are severely limited. The development of novel anti-obesity drugs is fraught with efficacy and safety issues. Consequently, several investigational anti-obesity drugs have failed to gain marketing approval in recent years. Anorectic gut hormones offer a potentially safe and viable option for the treatment of obesity. The prospective utility of gut hormones has improved drastically in recent years with the development of longer acting analogues. Additionally, specific combinations of gut hormones have been demonstrated to have additive anorectic effects. This article reviews the current stage of anti-obesity drugs in development, focusing on gut hormone-based therapies. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  11. The future of tic disorder treatment.

    PubMed

    Bennett, Shannon M; Keller, Alex E; Walkup, John T

    2013-11-01

    Competing theories on the etiology and treatment of chronic tic disorders and Tourette syndrome have long made the search for efficacious intervention more challenging for patients and families seeking to reduce functional impairment related to tic symptoms. These symptoms were historically posited to be either psychological in origin, leading to the long tradition of psychoanalytic psychotherapy for tics, or biological in nature, particularly since the advent of successful treatments using neuroleptic medications. Current thinking about the phenomenology of tic disorders comes from growing empirical evidence as well as advances in neuroscience and genetics research and reveals a biological vulnerability that is exacerbated by physiological arousal related to environmental or interpersonal stress. This manuscript summarizes the evolution of this knowledge base and describes current best-practice recommendations for patients, families, and clinicians. © 2013 New York Academy of Sciences.

  12. Psychotherapy and Psychosocial Treatment: Recent Advances and Future Directions.

    PubMed

    Plakun, Eric M

    2015-09-01

    Psychotherapy and psychosocial treatment have been shown to be effective forms of treatment of a range of individual and complex comorbid disorders. The future role of psychotherapy and psychosocial treatment depends on several factors, including full implementation of mental health parity, correction of underlying false assumptions that shape treatment, payment priorities and research, identification and teaching of common factors or elements shared by effective psychosocial therapies, and adequate teaching of psychotherapy and psychosocial treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Current and future treatments for Alzheimer's disease.

    PubMed

    Salloway, Stephen

    2009-08-01

    There are currently >5 million people in the United States who have been diagnosed with Alzheimer's disease. That prevalence rate is expected to triple as the population ages. The health and economic burden due to Alzheimer's disease is a worldwide problem, with some of the greatest burden coming from the developing world as people live longer in those societies. Throughout the world, the projected growth of Alzheimer's disease is dramatic. This is a worldwide public health problem of the highest order, and there is a compelling need to develop new treatments and methods of earlier diagnosis need to slow the progression of the disease and lessen its impact.

  14. Fetal ventriculomegaly: Diagnosis, treatment, and future directions.

    PubMed

    Pisapia, Jared M; Sinha, Saurabh; Zarnow, Deborah M; Johnson, Mark P; Heuer, Gregory G

    2017-07-01

    Fetal ventriculomegaly (VM) refers to the enlargement of the cerebral ventricles in utero. It is associated with the postnatal diagnosis of hydrocephalus. VM is clinically diagnosed on ultrasound and is defined as an atrial diameter greater than 10 mm. Because of the anatomic detailed seen with advanced imaging, VM is often further characterized by fetal magnetic resonance imaging (MRI). Fetal VM is a heterogeneous condition with various etiologies and a wide range of neurodevelopmental outcomes. These outcomes are heavily dependent on the presence or absence of associated anomalies and the direct cause of the ventriculomegaly rather than on the absolute degree of VM. In this review article, we discuss diagnosis, work-up, counseling, and management strategies as they relate to fetal VM. We then describe imaging-based research efforts aimed at using prenatal data to predict postnatal outcome. Finally, we review the early experience with fetal therapy such as in utero shunting, as well as the advances in prenatal diagnosis and fetal surgery that may begin to address the limitations of previous therapeutic efforts.

  15. Future treatments of allergic diseases and asthma.

    PubMed

    Stirling, R G; Chung, K F

    2000-01-01

    Recent advances in the understanding of the inflammatory and immunological mechanisms of allergic diseases have illuminated many potential therapeutic strategies that may prevent or even reverse the abnormalities of allergic inflammation. As the roles of effector cells, and of signalling and adhesion molecules are better understood, the opportunities to inhibit or prevent the inflammatory cascade have increased. In addition, there have been advances in the synthesis of proteins, monoclonal antibodies and new small molecule chemical entities, which provide further valuable flexibility in the therapeutic approach to asthma. Such new approaches are aimed at prevention of T-cell activation; redressing the imbalance of T helper cell populations thus inhibiting or preventing Th-2-derived cytokine expression; and the inhibition or blockade of the downstream actions of these cytokines such as effects on IgE and eosinophils. Approaches such as these allow both broad and highly specific targeting, and may pave the way towards the prevention and reversal of the immunological and inflammatory processes driving asthma, allergic rhinitis and atopic dermatitis. The development of effective agents with effects beyond those provided by current therapies coupled with lesser side-effects will further address the unmet needs of allergic disease.

  16. Water quality monitoring strategies - A review and future perspectives.

    PubMed

    Behmel, S; Damour, M; Ludwig, R; Rodriguez, M J

    2016-11-15

    The reliable assessment of water quality through water quality monitoring programs (WQMPs) is crucial in order for decision-makers to understand, interpret and use this information in support of their management activities aiming at protecting the resource. The challenge of water quality monitoring has been widely addressed in the literature since the 1940s. However, there is still no generally accepted, holistic and practical strategy to support all phases of WQMPs. The purpose of this paper is to report on the use cases a watershed manager has to address to plan or optimize a WQMP from the challenge of identifying monitoring objectives; selecting sampling sites and water quality parameters; identifying sampling frequencies; considering logistics and resources to the implementation of actions based on information acquired through the WQMP. An inventory and critique of the information, approaches and tools placed at the disposal of watershed managers was proposed to evaluate how the existing information could be integrated in a holistic, user-friendly and evolvable solution. Given the differences in regulatory requirements, water quality standards, geographical and geological differences, land-use variations, and other site specificities, a one-in-all solution is not possible. However, we advance that an intelligent decision support system (IDSS) based on expert knowledge that integrates existing approaches and past research can guide a watershed manager through the process according to his/her site-specific requirements. It is also necessary to tap into local knowledge and to identify the knowledge needs of all the stakeholders through participative approaches based on geographical information systems and adaptive survey-based questionnaires. We believe that future research should focus on developing such participative approaches and further investigate the benefits of IDSS's that can be updated quickly and make it possible for a watershed manager to obtain a

  17. Treatment strategy for urinary frequency in women.

    PubMed

    Hsieh, Ching-Hung; Su, Tsung-Hsien

    2017-01-01

    The purpose of this paper is to discuss the differential diagnosis of the underlying etiologies of urinary frequency and the treatment strategies for urinary frequency in women. Urinary frequency is a symptom, a sign, and a condition of uncertainty and of multifactorial cause. Common causes of urinary frequency include psychosocial, medical, sexual, urological, gynecologic, endocrine, and pharmacological in origin. Hence, treatment of symptoms and possible cures need a high-level plan or strategy to overcome the multifactorial etiology. Proper investigation of the chief complaint, history and physical examinations, is needed to evaluate urinary frequency. Pregnancy test, wet smear, urinalysis, midstream urine culture, frequency-volume charts, cystourethroscopy, urodynamics, and genitourinary imaging are the basic routine of office investigations. These tools promote the accuracy of the differential diagnosis of the underlying cause of urinary frequency. It is then often helpful to adopt an algorithmic approach to the management of this complaint. Treatment of urinary frequency might be empirical, and it remains a clinical challenge to gynecologists. To cure the disease, it is important to listen to the patient and consider the condition in all its aspects and use proven techniques. © 2017 Japan Society of Obstetrics and Gynecology.

  18. Treatment Strategies for Intracranial Mirror Aneurysms.

    PubMed

    Wang, Wen-Xin; Xue, Zhe; Li, Lin; Wu, Chen; Zhang, Yan-Yang; Lou, Xin; Ma, Lin; Sun, Zheng-Hui

    2017-04-01

    Intracranial mirror aneurysms are clinically rare and uncommonly reported in the literature. Therefore, the present study evaluated a series of mirror aneurysm cases with respect to the clinical features of the patients and the treatment strategies that were used. This study retrospectively reviewed and systematically analyzed the clinical features, imaging data, treatment methods, and treatment outcomes of 68 cases of mirror aneurysms (a total of 70 pairs) in patients who were admitted to our department between November 2007 and May 2016. The patient population included 24 male and 44 female patients, with a mean age of 52 years. The mirror aneurysms were primarily located in posterior communicating artery and middle cerebral artery and 65 of the aneurysms were large or giant (≧10 mm). Of the 68 patients, 28 were treated by the clipping or embolization of all aneurysms in one stage, 16 were treated in 2 stages, 16 were treated by treating part of the aneurysms, and 8 were observed. The modified Rankin Scale scores of the 60 patients that were treated indicated that 52 had a good recovery (modified Rankin Scale score ≦2; 86.7%), and 1 patient died. Treatment strategies for mirror aneurysms should be determined individually according to the location, size, and morphology of the aneurysm, as well as the clinical manifestations of each patient. Furthermore, the responsible ruptured aneurysm should be given treatment priority, whereas the contralateral unruptured aneurysm should be observed or treated in either 1 or 2 stages. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Future treatment options for human African trypanosomiasis.

    PubMed

    Jones, Amy J; Avery, Vicky M

    2015-01-01

    Over the past 17 years, the number of reported cases of human African trypanosomiasis (HAT) has declined by over 90%, a significant result since the disease was highlighted as a public health problem by the WHO in 1995. However, if the goal of eliminating HAT by 2020 is to be achieved, then new treatments need to be identified and developed. A plethora of compound collections has been screened against Trypanosoma brucei spp, the etiological agents of HAT, resulting in three compounds progressing to clinical development. However, due to the high attrition rates in drug discovery, it is essential that research continues to identify novel molecules. Failure to do so, will result in the absence of molecules in the pipeline to fall back on should the current clinical trials be unsuccessful. This could seriously compromise control efforts to date, resulting in a resurgence in the number of HAT cases.

  20. TASC (Treatment Alternatives to Street Crime): Historical Perspective and Future Implications

    ERIC Educational Resources Information Center

    Mecca, Andrew M.

    1978-01-01

    This paper reviews the historical metamorphosis of the concept of treatment and emergence of TASC as a federal strategy for effecting a criminal justice-health care interface to deal with drug abusers. Impact of the TASC program is discussed as well as implications for future efforts. (Author)

  1. Novel treatment strategies in rheumatoid arthritis.

    PubMed

    Burmester, Gerd R; Pope, Janet E

    2017-06-10

    New treatment strategies have substantially changed the course of rheumatoid arthritis. Many patients can achieve remission if the disease is recognised early and is treated promptly and continuously; however, some individuals do not respond adequately to treatment. Rapid diagnosis and a treat-to-target approach with tight monitoring and control, can increase the likelihood of remission in patients with rheumatoid arthritis. In this Series paper, we describe new insights into the management of rheumatoid arthritis with targeted therapy approaches using classic and novel medications, and outline the potential effects of precision medicine in this challenging disease. Articles are included that investigate the treat-to-target approach, which includes adding or de-escalating treatment. Rheumatoid arthritis treatment is impeded by delayed diagnosis, problematic access to specialists, and difficulties adhering to treat-to-target principles. Clinical management goals in rheumatoid arthritis include enabling rapid access to optimum diagnosis and care and the well informed use of multiple treatments approved for this disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Predicting Future Clinical Adjustment from Treatment Outcome and Process Variables.

    ERIC Educational Resources Information Center

    Patterson, G. R.; Forgatch, Marion S.

    1995-01-01

    Issues related to the use of outcome and process data from the treatment of antisocial children to predict future childhood adjustment were examined through a study of 69 children. Data supported the hypothesis that measures of processes thought to produce changes in child behavior would serve to predict future adjustment. (SLD)

  3. Anti-GD2 Strategy in the Treatment of Neuroblastoma

    PubMed Central

    Yang, Richard K.; Sondel, Paul M.

    2010-01-01

    The prognosis for advanced neuroblastoma remains poor with high risk of recurrence after consolidation. Therapies based on monoclonal antibodies that specifically target disialoganglioside GD2 on tumor cells are improving treatment results for high-risk neuroblastoma. This article reviews the use of anti-GD2 antibodies either as monotherapy or as part of a larger and more complex treatment approach for advanced neuroblastoma. We review how anti-GD2 antibodies can be combined with other treatments or strategies to enhance their clinical effects. Tumor resistance and other problems that decrease the efficacy of anti-GD2 antibodies are discussed. Future developments in the area of anti-GD2 immunotherapies for neuroblastoma are also addressed. PMID:21037966

  4. Antisense Oligonucleotides: Treatment Strategies and Cellular Internalization

    PubMed Central

    Miller, Colton M.; Harris, Edward N.

    2016-01-01

    The clinical applicaton of antisense oligonucleotides (ASOs) is becoming more of a reality as several drugs have been approved for the treatment of human disorders and many others are in various phases in development and clinical trials. ASOs are short DNA/RNA oligos which are heavily modified to increase their stability in biological fluids and retain the properties of creating RNA-RNA and DNA-RNA duplexes that knock-down or correct genetic expression. This review outlines several strategies that ASOs utilize for the treatment of various congenital diseases and syndromes that develop with aging. In addition, we discuss some of the mechanisms for specific non-targeted ASO internalization within cells. PMID:28374018

  5. Clostridium difficile outbreaks: prevention and treatment strategies

    PubMed Central

    Martinez, Fernando J; Leffler, Daniel A; Kelly, Ciaran P

    2012-01-01

    The incidence and severity of Clostridium difficile infection (CDI) have increased dramatically over the past decade. Its treatment, however, has largely remained the same with the exception of oral vancomycin use as a first-line agent in severe disease. From 1999 to 2004, 20,642 deaths were attributed to CDI in the United States, almost 7 times the rate of all other intestinal infections combined. Worldwide, several major CDI outbreaks have occurred, and many of these were associated with the NAP1 strain. This ‘epidemic’ strain has contributed to the rising incidence and mortality of CDI. The purpose of this article is to review the current management, treatment, infection control, and prevention strategies that are needed to combat this increasingly morbid disease. PMID:22826646

  6. Preparing Future Leaders: Project Management Strategies for Service Learning

    ERIC Educational Resources Information Center

    Munger, Roger; Gutowski, Amanda

    2008-01-01

    This article makes a case for teaching project management strategies in service-learning courses. The authors describe three specific documents students can create to help them manage a service-learning project and then present strategies that can help students manage their project teams. Such skills, the authors argue, provide the tools students…

  7. Preparing Future Leaders: Project Management Strategies for Service Learning

    ERIC Educational Resources Information Center

    Munger, Roger; Gutowski, Amanda

    2008-01-01

    This article makes a case for teaching project management strategies in service-learning courses. The authors describe three specific documents students can create to help them manage a service-learning project and then present strategies that can help students manage their project teams. Such skills, the authors argue, provide the tools students…

  8. Systematic Treatment Selection (STS): A Review and Future Directions

    ERIC Educational Resources Information Center

    Nguyen, Tam T.; Bertoni, Matteo; Charvat, Mylea; Gheytanchi, Anahita; Beutler, Larry E.

    2007-01-01

    Systematic Treatment Selection (STS) is a form of technical eclectism that develops and plans treatments using empirically founded principles of psychotherapy. It is a model that provides systematic guidelines for the utilization of different psychotherapeutic strategies based on patient qualities and problem characteristics. Historically, it…

  9. Biological treatment strategies for disc degeneration: potentials and shortcomings

    PubMed Central

    Nerlich, Andreas G.; Boos, Norbert

    2006-01-01

    Recent advances in molecular biology, cell biology and material sciences have opened a new emerging field of techniques for the treatment of musculoskeletal disorders. These new treatment modalities aim for biological repair of the affected tissues by introducing cell-based tissue replacements, genetic modifications of resident cells or a combination thereof. So far, these techniques have been successfully applied to various tissues such as bone and cartilage. However, application of these treatment modalities to cure intervertebral disc degeneration is in its very early stages and mostly limited to experimental studies in vitro or in animal studies. We will discuss the potential and possible shortcomings of current approaches to biologically cure disc degeneration by gene therapy or tissue engineering. Despite the increasing number of studies examining the therapeutic potential of biological treatment strategies, a practicable solution to routinely cure disc degeneration might not be available in the near future. However, knowledge gained from these attempts might be applied in a foreseeable future to cure the low back pain that often accompanies disc degeneration and therefore be beneficial for the patient. PMID:16983559

  10. Adjuvant treatment of GIST: patient selection and treatment strategies.

    PubMed

    Joensuu, Heikki

    2012-04-24

    Tyrosine kinase inhibitors that target the key molecular drivers of gastrointestinal stromal tumour (GIST) are effective treatments of advanced-stage GIST. Yet, most of these patients succumb to the disease. Approximately 60% of patients with GIST are cured by surgery, and these individuals can be identified by risk stratification schemes based on tumour size, mitosis count and site, and assessment of rupture. Two large randomized trials have evaluated imatinib as adjuvant treatment for operable, KIT-positive GIST; adjuvant imatinib substantially improved time to recurrence. One of these trials reported that 3 years of adjuvant imatinib improves overall survival of patients who have a high estimated risk for recurrence of GIST compared with 1 year of imatinib. The optimal adjuvant strategy remains unknown and some patients might benefit from longer than 3 years of imatinib treatment. However, a strategy that involves GIST risk assessment following surgery using a validated scheme, administration of adjuvant imatinib for 3 years, patient monitoring during and after completion of imatinib to detect recurrence early, and reinstitution of imatinib if GIST recurs is a reasonable choice for care of patients with high-risk GIST.

  11. Futurism.

    ERIC Educational Resources Information Center

    Foy, Jane Loring

    The objectives of this research report are to gain insight into the main problems of the future and to ascertain the attitudes that the general population has toward the treatment of these problems. In the first section of this report the future is explored socially, psychologically, and environmentally. The second section describes the techniques…

  12. Inventing the Future: Options and Strategies for Educators.

    ERIC Educational Resources Information Center

    Burdin, Joel L.; And Others

    1984-01-01

    An overview of alternative futurism and implications and applications for the elementary and secondary grades are provided in this article. The teacher's role is explored in a discussion of development of educational personnel. (DF)

  13. Inventing the Future: Options and Strategies for Educators.

    ERIC Educational Resources Information Center

    Burdin, Joel L.; And Others

    1984-01-01

    An overview of alternative futurism and implications and applications for the elementary and secondary grades are provided in this article. The teacher's role is explored in a discussion of development of educational personnel. (DF)

  14. Breast cancer. Part 2: present and future treatment modalities.

    PubMed

    Harmer, Victoria

    This is the second article in a series of three on breast cancer. Part 1 discussed breast anatomy, the principles behind breast awareness and breast health, detailing common benign breast diseases, types of breast cancer and staging. In this article, treatment for breast cancer is discussed. The article will follow the usual order of modalities in the trajectory, starting with surgery, then chemotherapy, radiotherapy and endocrine treatment, finishing with a discussion of future and biological treatments.

  15. Optimal scan strategies for future CMB satellite experiments

    NASA Astrophysics Data System (ADS)

    Wallis, Christopher G. R.; Brown, Michael L.; Battye, Richard A.; Delabrouille, Jacques

    2017-04-01

    The B-mode polarization power spectrum in the cosmic microwave background (CMB) is about four orders of magnitude fainter than the CMB temperature power spectrum. Any instrumental imperfections that couple temperature fluctuations to B-mode polarization must therefore be carefully controlled and/or removed. We investigate the role that a scan strategy can have in mitigating certain common systematics by averaging systematic errors down with many crossing angles. We present approximate analytic forms for the error on the recovered B-mode power spectrum that would result from differential gain, differential pointing and differential ellipticity for the case where two detector pairs are used in a polarization experiment. We use these analytic predictions to search the parameter space of common satellite scan strategies in order to identify those features of a scan strategy that have most impact in mitigating systematic effects. As an example, we go on to identify a scan strategy suitable for the CMB satellite proposed for the European Space Agency M5 call, considering the practical considerations of fuel requirement, data rate and the relative orientation of the telescope to the earth. Having chosen a scan strategy we then go on to investigate the suitability of the scan strategy.

  16. Current status and future strategies of cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis

    PubMed Central

    al-Shammaa, Hassan Alaa Hammed; Li, Yan; Yonemura, Yutaka

    2008-01-01

    This article is to offer a concise review on the use of cytoreductive surgery (CRS) plus intraperitoneal hyperthermic chemotherapy (IPHC) for the treatment of peritoneal carcinomatosis (PC). Traditionally, PC was treated with systemic chemotherapy alone with very poor response and a median survival of less than 6 mo. With the establishment of several phase II studies, a new trend has been developed toward the use of CRS plus IPHC as a standard method for treating selected patients with PC, in whom sufficient cytoreduction could be achieved. In spite of the need for more high quality phase III studies, there is now a consensus among many surgical oncology experts throughout the world about the use of this new treatment strategy as standard care for colorectal cancer patients with PC. This review summarizes the current status and possible progress in future. PMID:18300340

  17. Inhalation injury: epidemiology, pathology, treatment strategies

    PubMed Central

    2013-01-01

    Lung injury resulting from inhalation of smoke or chemical products of combustion continues to be associated with significant morbidity and mortality. Combined with cutaneous burns, inhalation injury increases fluid resuscitation requirements, incidence of pulmonary complications and overall mortality of thermal injury. While many products and techniques have been developed to manage cutaneous thermal trauma, relatively few diagnosis-specific therapeutic options have been identified for patients with inhalation injury. Several factors explain slower progress for improvement in management of patients with inhalation injury. Inhalation injury is a more complex clinical problem. Burned cutaneous tissue may be excised and replaced with skin grafts. Injured pulmonary tissue must be protected from secondary injury due to resuscitation, mechanical ventilation and infection while host repair mechanisms receive appropriate support. Many of the consequences of smoke inhalation result from an inflammatory response involving mediators whose number and role remain incompletely understood despite improved tools for processing of clinical material. Improvements in mortality from inhalation injury are mostly due to widespread improvements in critical care rather than focused interventions for smoke inhalation. Morbidity associated with inhalation injury is produced by heat exposure and inhaled toxins. Management of toxin exposure in smoke inhalation remains controversial, particularly as related to carbon monoxide and cyanide. Hyperbaric oxygen treatment has been evaluated in multiple trials to manage neurologic sequelae of carbon monoxide exposure. Unfortunately, data to date do not support application of hyperbaric oxygen in this population outside the context of clinical trials. Cyanide is another toxin produced by combustion of natural or synthetic materials. A number of antidote strategies have been evaluated to address tissue hypoxia associated with cyanide exposure. Data

  18. Treatment strategies for programming and ritual abuse.

    PubMed

    Ross, Colin

    2017-02-16

    Individuals in treatment for dissociative identity disorder not uncommonly describe childhood involvement in organized, multi-perpetrator ritual abuse. They described being "programmed" by the perpetrators and feel that the programming is out of their control. The author has developed a set of treatment strategies and interventions for such cases. These are based on the principle of therapeutic neutrality and can be used no matter what assumptions the therapist makes about the historical accuracy of the memories and beliefs. In ritual abuse cases, there are commonly "cult alters" who express allegiance to and identification with the perpetrators, and who state the ideology of the cult as personal beliefs. Often, the host personality holds and expresses the opposite half of the ambivalent attachment to the perpetrators: the host takes the position of helpless, powerless victim of the cult alters and programming, and wants to be rescued and "deprogrammed" by the therapist. This is a victim-rescuer-perpetrator triangle re-enactment. The perpetrator introjects involved in the re-enactment can be engaged in the therapy, and can become allies in recovery and the process of integration. Techniques for accomplishing this are described.

  19. Human Papillomavirus: Current and Future RNAi Therapeutic Strategies for Cervical Cancer

    PubMed Central

    Jung, Hun Soon; Rajasekaran, Nirmal; Ju, Woong; Shin, Young Kee

    2015-01-01

    Human papillomaviruses (HPVs) are small DNA viruses; some oncogenic ones can cause different types of cancer, in particular cervical cancer. HPV-associated carcinogenesis provides a classical model system for RNA interference (RNAi) based cancer therapies, because the viral oncogenes E6 and E7 that cause cervical cancer are expressed only in cancerous cells. Previous studies on the development of therapeutic RNAi facilitated the advancement of therapeutic siRNAs and demonstrated its versatility by siRNA-mediated depletion of single or multiple cellular/viral targets. Sequence-specific gene silencing using RNAi shows promise as a novel therapeutic approach for the treatment of a variety of diseases that currently lack effective treatments. However, siRNA-based targeting requires further validation of its efficacy in vitro and in vivo, for its potential off-target effects, and of the design of conventional therapies to be used in combination with siRNAs and their drug delivery vehicles. In this review we discuss what is currently known about HPV-associated carcinogenesis and the potential for combining siRNA with other treatment strategies for the development of future therapies. Finally, we present our assessment of the most promising path to the development of RNAi therapeutic strategies for clinical settings. PMID:26239469

  20. Pedagogical Strategies for Training Future Technicians in American Aviation Schools

    ERIC Educational Resources Information Center

    Pazyura, Natalia

    2015-01-01

    The article is devoted to the question of improvement of quality and efficiency of professional training of future technicians in aviation industry in the American educational establishments. Main attention is paid to the studies of pedagogical technologies, which are used for the sake of qualitative and efficient training of specialists of…

  1. Naval S and T Strategy: Innovations for the Future Force

    DTIC Science & Technology

    2015-01-20

    breakthrough solutions that shape the future force (e.g., Global Positioning System (GPS), radar, autonomous systems, graphene , QuikClot and many more...agencies including the Department of Energy (fuel cells, batteries , etc.) and the Department of Agriculture (biofuels). Recent conflicts have...concentrated solar systems; fuel cells; low-energy approaches to desalination and water purification; improved rechargeable batteries ; and efficient

  2. Project: Strategies for Sex Fairness. Changing Lives: Future Trends.

    ERIC Educational Resources Information Center

    Mook, Corena; Legg, Marilyn

    One of a series of instructional packets to aid schools in reducing sex stereotyping, this inservice guide for use with school personnel is intended to stimulate thought and discussion about the changes in occupational outlook for young adults over the past decades and prospects for the future. Focus is on socioeconomic changes already affecting…

  3. Pedagogical Strategies for Training Future Technicians in American Aviation Schools

    ERIC Educational Resources Information Center

    Pazyura, Natalia

    2015-01-01

    The article is devoted to the question of improvement of quality and efficiency of professional training of future technicians in aviation industry in the American educational establishments. Main attention is paid to the studies of pedagogical technologies, which are used for the sake of qualitative and efficient training of specialists of…

  4. A Critical Look at Communication Strategies: Possibilities for Future Research

    ERIC Educational Resources Information Center

    Doqaruni, Vahid Rahmani

    2015-01-01

    Like general theories of human communication, previous research into second language (L2) communication strategies (CSs) has also been characterized on either interactional conceived account or cognitively conceived one. However, this paper is a critical attempt to show that CSs' full significance can only be understood if the domain of CSs…

  5. Gypchek®: past and future strategies for use

    Treesearch

    J. D. Podgwaite

    1985-01-01

    The development of the gypsy moth nucleopolyhedrosis virus product Gypchek, and strategies for its use, have been largely patterned after conventional pesticide technology. Prior to Gypchek registration with the Environmental Protection Agency in 1978, several field tests involving variations in virus product, application hardware, dose rates, timing and formulation...

  6. A Critical Look at Communication Strategies: Possibilities for Future Research

    ERIC Educational Resources Information Center

    Doqaruni, Vahid Rahmani

    2015-01-01

    Like general theories of human communication, previous research into second language (L2) communication strategies (CSs) has also been characterized on either interactional conceived account or cognitively conceived one. However, this paper is a critical attempt to show that CSs' full significance can only be understood if the domain of CSs…

  7. Strategy and Communication: A Framework for Future International Relations.

    ERIC Educational Resources Information Center

    Roshwald, Mordecai

    1984-01-01

    World conditions make clarity of intent and substance essential in communications among governments. To avoid nuclear confrontation, strategy planners and policymakers should analyze their own communications as well as those of others with great care. Direct and fast communication among leaders can help to preserve peace. (Author/CS)

  8. Treatment for primary hypothyroidism: current approaches and future possibilities

    PubMed Central

    Chakera, Ali J; Pearce, Simon HS; Vaidya, Bijay

    2012-01-01

    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

  9. Future trends in environmental mercury concentrations: implications for prevention strategies.

    PubMed

    Sunderland, Elsie M; Selin, Noelle E

    2013-01-07

    In their new paper, Bellanger and coauthors show substantial economic impacts to the EU from neurocognitive impairment associated with methylmercury (MeHg) exposures. The main source of MeHg exposure is seafood consumption, including many marine species harvested from the global oceans. Fish, birds and other wildlife are also susceptible to the impacts of MeHg and already exceed toxicological thresholds in vulnerable regions like the Arctic. Most future emissions scenarios project a growth or stabilization of anthropogenic mercury releases relative to present-day levels. At these emissions levels, inputs of mercury to ecosystems are expected to increase substantially in the future, in part due to growth in the legacy reservoirs of mercury in oceanic and terrestrial ecosystems. Seawater mercury concentration trajectories in areas such as the North Pacific Ocean that supply large quantities of marine fish to the global seafood market are projected to increase by more than 50% by 2050. Fish mercury levels and subsequent human and biological exposures are likely to also increase because production of MeHg in ocean ecosystems is driven by the supply of available inorganic mercury, among other factors. Analyses that only consider changes in primary anthropogenic emissions are likely to underestimate the severity of future deposition and concentration increases associated with growth in mercury reservoirs in the land and ocean. We therefore recommend that future policy analyses consider the fully coupled interactions among short and long-lived reservoirs of mercury in the atmosphere, ocean, and terrestrial ecosystems. Aggressive anthropogenic emission reductions are needed to reduce MeHg exposures and associated health impacts on humans and wildlife and protect the integrity of one of the last wild-food sources globally. In the near-term, public health advice on safe fish consumption choices such as smaller species, younger fish, and harvests from relatively unpolluted

  10. Bridge to a sustainable future: National environmental technology strategy

    SciTech Connect

    1995-04-01

    For the past two years the Administration has sought the views of Congress, the states, communities, industry, academia, nongovernmental organizations, and interested citizens on ways to spur the development and use of a new generation of environmental technologies. This document represents the views of thousands of individuals who participated in events around the country to help craft a national environmental technology strategy that will put us on the path to sustainable development.

  11. Tactical Fuel and Energy Strategy for The Future Modular Force

    DTIC Science & Technology

    2009-05-18

    product of the anaerobic digestion (decomposition without oxygen) of organic matter such as animal manure , sewage, and municipal solid waste. It is...supplement petroleum-based fuels and thereby decrease petroleum-based fuel requirements. The Army can stage itself through additional and increased R&D...Energy situation and to begin to develop flexible options and recommend choices and investments that will yield a balanced strategy. At this stage

  12. Treatment strategies for huge central neurocytomas.

    PubMed

    Xiong, Zhong-wei; Zhang, Jian-jian; Zhang, Ting-bao; Sun, Shou-jia; Wu, Xiao-lin; Wang, Hao; You, Chao; Wang, Yu; Zhang, Hua-qiu; Chen, Jin-cao

    2015-02-01

    Central neurocytomas (CNs), initially asymptomatic, sometimes become huge before detection. We described and analyzed the clinical, radiological, operational and outcome data of 13 cases of huge intraventricular CNs, and discussed the treatment strategies in this study. All huge CNs (n=13) in our study were located in bilateral lateral ventricle with diameter ≥5.0 cm and had a broad-based attachment to at least one side of the ventricle wall. All patients received craniotomy to remove the tumor through transcallosal or transcortical approach and CNs were of typical histologic and immunohistochemical features. Adjuvant therapies including conventional radiation therapy (RT) or gamma knife radiosurgery (GKRS) were also performed postoperatively. Transcallosal and transcortical approaches were used in 8 and 5 patients, respectively. Two patients died within one month after operation and 3 patients with gross total resection (GTR) were additionally given a decompressive craniectomy (DC) and/or ventriculoperitoneal shunt (VPS) as the salvage therapy. Six patients received GTR(+RT) and 7 patients received subtotal resection (STR)(+GKRS). Eight patients suffered serious complications such as hydrocephalus, paralysis and seizure after operation, and patients who underwent GTR showed worse functional outcome [less Karnofsky performance scale (KPS) scores] than those having STR(+GKRS) during the follow-up period. The clinical outcome of huge CNs seemed not to be favorable as that described in previous reports. Surgical resection for huge CNs should be meticulously considered to guarantee the maximum safety. Better results were achieved in STR(+GKRS) compared with GTR(+RT) for huge CNs, suggesting that STR(+GKRS) may be a better treatment choice. The recurrent or residual tumor can be treated with GKRS effectively.

  13. Anti-VEGF Treatment Strategies for Wet AMD.

    PubMed

    Kovach, Jaclyn L; Schwartz, Stephen G; Flynn, Harry W; Scott, Ingrid U

    2012-01-01

    Over the past few years, antivascular endothelial growth factor (VEGF) therapy has become a standard treatment for neovascular age-related macular degeneration (AMD). During this time, treatment strategies have evolved from a monthly dosing schedule to individualized regimens. This paper will review the currently available anti-VEGF agents and evidence-based treatment strategies.

  14. Anti-VEGF Treatment Strategies for Wet AMD

    PubMed Central

    Kovach, Jaclyn L.; Schwartz, Stephen G.; Flynn, Harry W.; Scott, Ingrid U.

    2012-01-01

    Over the past few years, antivascular endothelial growth factor (VEGF) therapy has become a standard treatment for neovascular age-related macular degeneration (AMD). During this time, treatment strategies have evolved from a monthly dosing schedule to individualized regimens. This paper will review the currently available anti-VEGF agents and evidence-based treatment strategies. PMID:22523653

  15. [Future Regulatory Science through a Global Product Development Strategy to Overcome the Device Lag].

    PubMed

    Tsuchii, Isao

    2016-01-01

    Environment that created "medical device lag (MDL)" has changed dramatically, and currently that term is not heard often. This was mainly achieved through the leadership of three groups: government, which determined to overcome MDL and took steps to do so; medical societies, which exhibited accountability in trial participation; and MD companies, which underwent a change in mindset that allowed comprehensive tripartite cooperation to reach the current stage. In particular, the global product development strategy (GPDS) of companies in a changing social environment has taken a new-turn with international harmonization trends, like Global Harmonization Task Force and International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. As a result, this evolution has created opportunities for treatment with cutting-edge MDs in Japanese society. Simultaneously, it has had a major impact on the planning process of GPDS of companies. At the same time, the interest of global companies has shifted to emerging economies for future potential profit since Japan no longer faces MDL issue. This economic trend makes MDLs a greater problem for manufacturers. From the regulatory science viewpoint, this new environment has not made it easy to plan a global strategy that will be adaptable to local societies. Without taking hasty action, flexible thinking from the global point of view is necessary to enable the adjustment of local strategies to fit the situation on the ground so that the innovative Japanese medical technology can be exported to a broad range of societies.

  16. Archiving strategy for USGS EROS center and our future direction

    USGS Publications Warehouse

    Faundeen, John L.

    2010-01-01

    The U. S. Geological Survey's Earth Resources Observation and Science Center has the responsibility to acquire, manage, and preserve our Nation's land observations. These records are obtained primarily from airplanes and satellites dating back to the 1930s. The ability to compare landscapes from the past with current information enables change analysis at local and global scales. With new observations added daily, the records management challenges are daunting, involving petabytes of electronic data and tens of thousands of rolls of analog film. This paper focuses upon the appraisal and preservation functions employed to ensure that these records are available for current and future generations.

  17. Optimizing Hypoxia Detection and Treatment Strategies

    PubMed Central

    Koch, Cameron J.; Evans, Sydney M.

    2015-01-01

    Clinical studies using Eppendorf® needle sensors have invariably documented the resistance of hypoxic human tumors to therapy. These studies first documented the need for individual patient measurement of hypoxia, since hypoxia varied from tumor-to-tumor. Furthermore, hypoxia in sarcomas & cervical cancer leads to distant metastasis or local/regional spread, respectively. For various reasons, the field has moved away from direct needle-sensor oxygen measurements to indirect assays (HIF-related changes; bioreductive metabolism) and the latter can be imaged non-invasively. Many of hypoxia’s detrimental therapeutic effects are reversible in mice but little treatment-improvement in hypoxic human tumors has been seen. The question is why? What factors cause human tumors to be refractory to anti-hypoxia strategies? We suggest the primary cause to be the complexity of hypoxia formation and its characteristics. Three basic types of hypoxia exist, encompassing various diffusional (distance from perfused vessel), temporal (on/off cycling) and perfusional (blood-flow efficiency) limitations. Surprisingly, there is no current information on their relative prevalence in human tumors and even animal models. This is important because different hypoxia sub-types are predicted to require different diagnostic and therapeutic approaches, but the implications of this remain unknown. Even more challenging, no agreement exists for the best way to measure hypoxia. Some results even suggest that hypoxia is unlikely to be targetable therapeutically. In this review, the authors will revisit various critical aspects of this field that are sometimes forgotten or misrepresented in the recent literature. Since most current non-invasive imaging studies involve PET-isotope-labelled 2-nitroimidazoles, we will emphasize key findings made in our studies using EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide] and F18-labelled EF5. These will show the importance of

  18. Oligometastatic non-small-cell lung cancer: current treatment strategies

    PubMed Central

    Richard, Patrick J; Rengan, Ramesh

    2016-01-01

    The oligometastatic disease theory was initially described in 1995 by Heilman 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. PMID:28210169

  19. Water management in cities of the future using emission control strategies for priority hazardous substances.

    PubMed

    Eriksson, E; Revitt, D M; Ledin, A; Lundy, L; Holten Lützhøft, H C; Wickman, T; Mikkelsen, P S

    2011-01-01

    Cities of the future face challenges with respect to the quantity and quality of water resources, and multiple managerial options need to be considered in order to safeguard urban surface water quality. In a recently completed project on 'Source control options for reducing emissions of Priority Pollutants' (ScorePP), seven emission control strategies (ECSs) were developed and tested within a semi-hypothetical case city (SHCC) to evaluate their potential to reduce the emission of selected European priority hazardous substances (PHSs) to surface waters. The ECSs included (1) business-as-usual, (2) full implementation of relevant European (EU) directives, (3) ECS2 in combination with voluntary options for household, municipalities and industry, (4) ECS2 combined with industrial treatment and best available technologies (BAT), (5) ECS2 in combination with stormwater and combined sewer overflow treatment, (6) ECS2 in combination with advanced wastewater treatment, and (7) combinations of ECS3-6. The SHCC approach was chosen to facilitate transparency, to allow compensating for data gaps and to decrease the level of uncertainty in the results. The selected PHSs: cadmium (Cd), hexachlorobenzene (HCB), nonylphenol (NP) and pentabromodiphenyl ether (PBDE) differ in their uses and environmental fate and therefore accumulate in surface waters to differing extents in response to the application of alternative ECS. To achieve the required reduction in PHS levels in urban waters the full implementation of existing EU regulation is prioritised and feasible combinations of managerial and technological options (source control and treatment) can be highly relevant for mitigating releases.

  20. Present, old and future strategies for anti-HCV treatment in patients infected by genotype-1: estimation of the drug costs in the Calabria Region in the era of the directly acting antivirals.

    PubMed

    Strazzulla, Alessio; Costa, Chiara; Pisani, Vincenzo; De Maria, Vincenzo; Giancotti, Francesca; Di Salvo, Sebastiano; Parisi, Saverio Giuseppe; Basso, Monica; Franzetti, Marzia Maria; Marascio, Nadia; Liberto, Maria Carla; Barreca, Giorgio Settimo; Lamberti, Angelo Giuseppe; Zicca, Emilia; Postorino, Maria Concetta; Matera, Giovanni; Focà, Alfredo; Torti, Carlo

    2014-01-01

    In Italy, anti-HCV drugs are provided free of charge by the National Health System. Since 2011, three drug regimens including a directly acting antiviral (DAA) are considered the gold standard for HCV treatment. However, these drugs add a significant cost (roughly €26,000) to the combination of pegylated-interferon-α/ribavirin (PEG-IFN/RBV), which before DAA represented the unique treatment. To provide the National Health System potential useful information, we estimated costs to provide anti-HCV drugs to treat a population experienced for PEG-INF/RBV. Genotype 1 HCV mono-infected or HIV/HCV co-infected individuals who were treated with PEG-IFN/RBV between 2008 and 2013 were included. The cost to treat these patients with PEG-IFN/RBV was calculated (cost 1). We also estimated costs if we had to treat these patients with a lead-in period of PEG-INF/RBV followed by PEG-IFN/RBV and a DAA in naïves (cost 2), in addition to cost 1 plus the estimated cost to re-treat with PEG-IFN/RBV and a DAA patients who had a relapse or a non response (cost 3). Moreover, all costs were normalized by SVR. Rates of foreseen response with DAA were obtained from literature data. The overall study population consisted of 104 patients. The rate of sustained virological response (SVR) was 55%, while it was estimated that SVR would be obtained in 75% of patients with a lead-in period with PEG-IFN/RBV followed by a DAA combination, and in 78% if this treatment is used to re-treat experienced patients with a DAA. Drug costs associated with these treatments were: €1,214,283 for cost 1, €3,474,977 for cost 2 and €3,002,095 for cost 3. Costs per SVR achieved were: €22,284 for cost 1, €44,643 for cost 2 and €38,322 for cost 3. Treatments including DAAs achieve a SVR in more patients than PEG-IFN/RBV but they cost around three times more than PEG-IFN/RBV alone regimens. Also, cost per SVR is almost twofold greater than PEG-IFN/RBV regimens. Therefore, it is mandatory to implement use

  1. Upcoming strategies for the treatment of metastatic melanoma.

    PubMed

    Spagnolo, Francesco; Queirolo, Paola

    2012-04-01

    Prognosis for advanced and metastatic melanoma is poor, with a 5-year survival of 78, 59 and 40% for patients with stage IIIA, IIIB and IIIC, respectively, and a 1-year survival of 62% for M1a, 53% for M1b and 33% for M1c. The unsatisfactory results of actual standard therapies for metastatic melanoma highlight the need for effective new therapeutic strategies. Several drugs, including BRAF, KIT and MEK inhibitors, are currently being evaluated after promising data from Phase I and Phase II studies; Vemurafenib, a BRAF-inhibitor agent, has been approved by the Food and Drug Administration (FDA) for the treatment of patients with unresectable or metastatic melanoma with the BRAF V600E mutation after a significant impact on both progression-free and overall survival was demonstrated compared with dacarbazine in a Phase III trial. Ipilimumab, an immunotherapeutic drug, has proven to be capable of inducing long-lasting responses and was approved for patients with advanced melanoma in first- and second-line treatment by the FDA and in second-line treatment by the European Medicines Agency. Furthermore, a significant survival benefit of the combination of ipilimumab with dacarbazine compared with dacarbazine alone for first-line treatment was reported. In the near future, patients with BRAF mutations could have the chance to benefit from treatment with BRAF inhibitors; patients harboring BRAF or NRAS mutations could be treated with MEK inhibitors; finally, the subgroup of patients with acral, mucosal or chronic sun-damaged melanoma harboring a KIT mutation could benefit from KIT inhibitors. Ipilimumab could become a standard treatment for metastatic melanoma, both as a single agent and in combination; its efficacy has been proven, and researchers should now address their efforts to understanding the predictive variables of response to treatment.

  2. Capability Investment Strategy to Enable JPL Future Space Missions

    NASA Technical Reports Server (NTRS)

    Lincoln, William; Merida, Sofia; Adumitroaie, Virgil; Weisbin, Charles R.

    2006-01-01

    The Jet Propulsion Laboratory (JPL) formulates and conducts deep space missions for NASA (the National Aeronautics and Space Administration). The Chief Technologist of JPL has responsibility for strategic planning of the laboratory's advanced technology program to assure that the required technological capabilities to enable future missions are ready as needed. The responsibilities include development of a Strategic Plan (Antonsson, E., 2005). As part of the planning effort, a structured approach to technology prioritization, based upon the work of the START (Strategic Assessment of Risk and Technology) (Weisbin, C.R., 2004) team, was developed. The purpose of this paper is to describe this approach and present its current status relative to the JPL technology investment.

  3. Temporal Investment Strategy to Enable JPL Future Space Missions

    NASA Technical Reports Server (NTRS)

    Lincoln, William P.; Hua, Hook; Weisbin, Charles R.

    2006-01-01

    The Jet Propulsion Laboratory (JPL) formulates and conducts deep space missions for NASA (the National Aeronautics and Space Administration). The Chief Technologist of JPL has the responsibility for strategic planning of the laboratory's advanced technology program to assure that the required technological capabilities to enable future JPL deep space missions are ready as needed; as such he is responsible for the development of a Strategic Plan. As part of the planning effort, he has supported the development of a structured approach to technology prioritization based upon the work of the START (Strategic Assessment of Risk and Technology) team. A major innovation reported here is the addition of a temporal model that supports scheduling of technology development as a function of time. The JPL Strategic Technology Plan divides the required capabilities into 13 strategic themes. The results reported here represent the analysis of an initial seven.

  4. Reducing Hospital Readmission: Current Strategies and Future Directions

    PubMed Central

    Kripalani, Sunil; Theobald, Cecelia N; Anctil, Beth; Vasilevskis, Eduard E

    2014-01-01

    New financial penalties for institutions with high readmission rates have intensified efforts to reduce rehospitalization. Several interventions that involve multiple components (e.g., patient needs assessment, medication reconciliation, patient education, arranging timely outpatient appointments, and providing telephone follow-up), have successfully reduced readmission rates for patients discharged to home. The effect of interventions on readmission rates is related to the number of components implemented, whereas single-component interventions are unlikely to reduce readmissions significantly. For patients discharged to post-acute care facilities, multicomponent interventions have reduced readmissions through enhanced communication, medication safety, advanced care planning, and enhanced training to manage common medical conditions that commonly precipitate readmission. To help hospitals direct resources and services to patients with greater likelihood of readmission, a number of risk stratification methods are available. Future work should better define the role of home-based services, information technology, mental health care, caregiver support, community partnerships, and new transitional care personnel. PMID:24160939

  5. Capability Investment Strategy to Enable JPL Future Space Missions

    NASA Technical Reports Server (NTRS)

    Lincoln, William; Merida, Sofia; Adumitroaie, Virgil; Weisbin, Charles R.

    2006-01-01

    The Jet Propulsion Laboratory (JPL) formulates and conducts deep space missions for NASA (the National Aeronautics and Space Administration). The Chief Technologist of JPL has responsibility for strategic planning of the laboratory's advanced technology program to assure that the required technological capabilities to enable future missions are ready as needed. The responsibilities include development of a Strategic Plan (Antonsson, E., 2005). As part of the planning effort, a structured approach to technology prioritization, based upon the work of the START (Strategic Assessment of Risk and Technology) (Weisbin, C.R., 2004) team, was developed. The purpose of this paper is to describe this approach and present its current status relative to the JPL technology investment.

  6. Temporal Investment Strategy to Enable JPL Future Space Missions

    NASA Technical Reports Server (NTRS)

    Lincoln, William P.; Hua, Hook; Weisbin, Charles R.

    2006-01-01

    The Jet Propulsion Laboratory (JPL) formulates and conducts deep space missions for NASA (the National Aeronautics and Space Administration). The Chief Technologist of JPL has the responsibility for strategic planning of the laboratory's advanced technology program to assure that the required technological capabilities to enable future JPL deep space missions are ready as needed; as such he is responsible for the development of a Strategic Plan. As part of the planning effort, he has supported the development of a structured approach to technology prioritization based upon the work of the START (Strategic Assessment of Risk and Technology) team. A major innovation reported here is the addition of a temporal model that supports scheduling of technology development as a function of time. The JPL Strategic Technology Plan divides the required capabilities into 13 strategic themes. The results reported here represent the analysis of an initial seven.

  7. Reducing hospital readmission rates: current strategies and future directions.

    PubMed

    Kripalani, Sunil; Theobald, Cecelia N; Anctil, Beth; Vasilevskis, Eduard E

    2014-01-01

    New financial penalties for institutions with high readmission rates have intensified efforts to reduce rehospitalization. Several interventions that involve multiple components (e.g., patient needs assessment, medication reconciliation, patient education, arranging timely outpatient appointments, and providing telephone follow-up) have successfully reduced readmission rates for patients discharged to home. The effect of interventions on readmission rates is related to the number of components implemented; single-component interventions are unlikely to reduce readmissions significantly. For patients discharged to postacute care facilities, multicomponent interventions have reduced readmissions through enhanced communication, medication safety, advanced care planning, and enhanced training to manage medical conditions that commonly precipitate readmission. To help hospitals direct resources and services to patients with greater likelihood of readmission, risk-stratification methods are available. Future work should better define the roles of home-based services, information technology, mental health care, caregiver support, community partnerships, and new transitional care personnel.

  8. Market Efficiency and the Risks and Returns of Dynamic Trading Strategies with Commodity Futures

    NASA Astrophysics Data System (ADS)

    Switzer, Lorne N.; Jiang, Hui

    This paper investigates relationships between profits from dynamic trading strategies, risk premium, convenience yields, and net hedging pressures for commodity futures. As a market efficiency study, it crosses a number of disciplines, including traditional finance, behavioral finance, and behavioral psychology. The term structure of oil, gold, copper and soybeans futures markets contains predictive power for the corresponding term premium. However, only oil futures and soybean futures lead their spot premium. Significant momentum profits are identified in both outright futures and spread trading strategies when the spot premium and the term premium are used to form winner and loser portfolios. Profits from active strategies based on winner and loser portfolios are conditioned on market structure and net hedging pressure effects. Dynamic trading strategies based on contracts with extreme backwardation, extreme contango, and extreme hedging pressures are also tested. On average, spread trading outperforms outright futures trading in capturing the term structure risk and hedging pressure risk. For such strategies, long-short the long-term spread offers the greatest and most significant return and it offers the only exploitable trading profits built on the past hedging pressure. The existence of profits from active trading strategies based on winners is consistent with behavioral finance and behavioral psychology models in which market participants irrationally overreact to information and trends.

  9. Removable partial dentures--treatment now and for the future.

    PubMed

    Jones, John D; Turkyilmaz, Ilser; Garcia, Lily T

    2010-04-01

    The use of a removable partial denture (RPD) in clinical practice remains a viable treatment modality. Various advancements have improved the quality of a RPD, subsequently improving the quality of life for the individuals that use them. This article describes four removable partial denture treatment modalities that provide valuable treatment for the partially edentulous patient. These modalities include: the implant supported RPD, attachment use in RPDs, rotational path RPDs, and Titanium and CAD/CAM RPDs. Data on future needs for RPDs indicate that while there is a decline in tooth loss in the U.S., the need for RPDs will actually increase as the population increases and ages. With the growth in the geriatric population, which includes a high percentage of partially edentulous patients, the use of RPDs in clinical treatment will continue to be predictable treatment option in clinical dentistry.

  10. Expectations, Fears, and Strategies: Juvenile Offender Thoughts on a Future outside of Incarceration

    ERIC Educational Resources Information Center

    Clinkinbeard, Samantha S.; Zohra, Tusty

    2012-01-01

    The current article explores the possible selves, or future expectations, of 543 incarcerated juvenile offenders in four Western states in the United States. We argue that juveniles who are able to articulate future expectations and fears and generate concrete strategies for achieving their goals have higher levels of motivational capital (i.e.,…

  11. Expectations, Fears, and Strategies: Juvenile Offender Thoughts on a Future outside of Incarceration

    ERIC Educational Resources Information Center

    Clinkinbeard, Samantha S.; Zohra, Tusty

    2012-01-01

    The current article explores the possible selves, or future expectations, of 543 incarcerated juvenile offenders in four Western states in the United States. We argue that juveniles who are able to articulate future expectations and fears and generate concrete strategies for achieving their goals have higher levels of motivational capital (i.e.,…

  12. Portfolio Strategies, Relinquishment, the Urban School System of the Future, and Smart Districts

    ERIC Educational Resources Information Center

    Hill, Paul; Jochim, Ashley; Campbell, Christine

    2013-01-01

    This brief outlines how new K-12 public education governance proposals--relinquishment, smart districts, and the urban school system of the future--are complements, not alternatives, to the portfolio strategy. The portfolio strategy defines the role of government, or how it can steer in public education; the other proposals show how, once…

  13. Amalgamation of Future Time Orientation, Epistemological Beliefs, Achievement Goals and Study Strategies: Empirical Evidence Established

    ERIC Educational Resources Information Center

    Phan, Huy P.

    2009-01-01

    Background: Recently research evidence emphasizes two main lines of inquiry, namely the relations between future time perspective (FTP), achievement goals (mastery, performance-approach, and performance-avoidance) and study processing strategies, and the relations between epistemological beliefs, achievement goals and study processing strategies.…

  14. Three Strategies...One Future. A "Crosswalk" among Three Proposals Shaping America's Workforce Preparation Policy.

    ERIC Educational Resources Information Center

    Employment and Training Administration (DOL), Boston, MA. Boston Regional Office.

    This paper briefly examines three publications that lay out strategies for U.S. economic competitiveness in the future: the U.S. Department of Education's report "America 2000: An Education Strategy," in response to the President's message of April 1991; the report of the Secretary of Labor's Commission on Achieving Necessary Skills…

  15. Pre-Service Teachers' Use of Reading Strategies in Their Own Readings and Future Classrooms

    ERIC Educational Resources Information Center

    Akyol, Hayati; Ulusoy, Mustafa

    2010-01-01

    The main purpose of this study was to determine pre-service teachers' use of reading strategies in their own readings. In addition, pre-service teachers' use of these strategies in their future teaching practices was also investigated. The subjects for this study were 505 pre-service teachers enrolled in one of the major universities in Ankara.…

  16. Emerging Therapeutic Strategies and Future Challenges in Clinical Periodontics.

    PubMed

    Shin, Daniel; Hamada, Yusuke; John, Vanchit

    2016-01-01

    Currently, the protocol for treating periodontitis follows a standardized and straightforward algorithm: 1) review and reinforce oral hygiene; 2) perform scaling and root planing; 3) proceed to periodontal surgery if the disease process has not been arrested; then 4) enroll the patient in a customized periodontal maintenance recall program to maintain the health of the reduced periodontium. Multiple longitudinal studies have demonstrated that the aforementioned treatment regimen can arrest the progression of periodontitis and can increase the likelihood of tooth retention and periodontal stability.

  17. Vaccination against Alzheimer disease: an update on future strategies.

    PubMed

    Fettelschoss, Antonia; Zabel, Franziska; Bachmann, Martin F

    2014-01-01

    Alzheimer disease is a devastating chronic disease without adequate therapy. More than 10 years ago, it was demonstrated in transgenic mouse models that vaccination may be a novel, disease-modifying therapy for Alzheimer. Subsequent clinical development has been a roller-coaster with some positive and many negative news. Here, we would like to summarize evidence that next generation vaccines optimized for old people and focusing on patients with mild disease stand a good chance to proof efficacious for the treatment of Alzheimer.

  18. Diffuse intrinsic pontine glioma-current status and future strategies.

    PubMed

    Khatua, Soumen; Moore, Kevin R; Vats, Tribh S; Kestle, John R W

    2011-09-01

    Diffuse intrinsic pontine gliomas which constitute 15% of all childhood brain tumors are inoperable and response to radiation and chemotherapy has not improved long-term survival. Due to lack of newer effective therapies, mean survival after diagnosis has remained less than 12 months. Trials investigating chemotherapy and/or radiation have proven disappointing. As biopsy of these tumors are rarely performed due to the high eloquence of the brain stem, information about the pathology and biology remains elusive hindering development of novel biologic agents. Poor access of most chemotherapeutic agents to these tumors due to the blood-brain barrier continues to undermine therapeutic efficacy. Thus, to date, we remain at a virtual standstill in our attempts to improve the prognosis of children with these tumors. An extensive review of the literature was performed concerning children with diffuse brain stem gliomas including clinical trials, evolving molecular biology, and newer therapeutic endeavors. A pivotal approach in improving the prognosis of these tumors should include the initiation of biopsy and encouraging families to consider autopsy to study the molecular biology. This will help in redefining this tumor by its molecular signature and profiling targeted therapy. Continued advances should be pursued in neuroimaging technology including identifying surrogate markers of early disease progression. Defining strategies to enhance local delivery of drugs into tumors with the help of newer surgical techniques are important. Exhaustive research in all these aspects as a multidisciplinary approach could provide hope to children with these fatal tumors.

  19. Evolving Strategies for Cancer and Autoimmunity: Back to the Future

    PubMed Central

    Lane, Peter J. L.; McConnell, Fiona M.; Anderson, Graham; Nawaf, Maher G.; Gaspal, Fabrina M.; Withers, David R.

    2014-01-01

    Although current thinking has focused on genetic variation between individuals and environmental influences as underpinning susceptibility to both autoimmunity and cancer, an alternative view is that human susceptibility to these diseases is a consequence of the way the immune system evolved. It is important to remember that the immunological genes that we inherit and the systems that they control were shaped by the drive for reproductive success rather than for individual survival. It is our view that human susceptibility to autoimmunity and cancer is the evolutionarily acceptable side effect of the immune adaptations that evolved in early placental mammals to accommodate a fundamental change in reproductive strategy. Studies of immune function in mammals show that high affinity antibodies and CD4 memory, along with its regulation, co-evolved with placentation. By dissection of the immunologically active genes and proteins that evolved to regulate this step change in the mammalian immune system, clues have emerged that may reveal ways of de-tuning both effector and regulatory arms of the immune system to abrogate autoimmune responses whilst preserving protection against infection. Paradoxically, it appears that such a detuned and deregulated immune system is much better equipped to mount anti-tumor immune responses against cancers. PMID:24782861

  20. Closed Fuel Cycle Waste Treatment Strategy

    SciTech Connect

    Vienna, J. D.; Collins, E. D.; Crum, J. V.; Ebert, W. L.; Frank, S. M.; Garn, T. G.; Gombert, D.; Jones, R.; Jubin, R. T.; Maio, V. C.; Marra, J. C.; Matyas, J.; Nenoff, T. M.; Riley, B. J.; Sevigny, G. J.; Soelberg, N. R.; Strachan, D. M.; Thallapally, P. K.; Westsik, J. H.

    2015-02-01

    This study is aimed at evaluating the existing waste management approaches for nuclear fuel cycle facilities in comparison to the objectives of implementing an advanced fuel cycle in the U.S. under current legal, regulatory, and logistical constructs. The study begins with the Global Nuclear Energy Partnership (GNEP) Integrated Waste Management Strategy (IWMS) (Gombert et al. 2008) as a general strategy and associated Waste Treatment Baseline Study (WTBS) (Gombert et al. 2007). The tenets of the IWMS are equally valid to the current waste management study. However, the flowsheet details have changed significantly from those considered under GNEP. In addition, significant additional waste management technology development has occurred since the GNEP waste management studies were performed. This study updates the information found in the WTBS, summarizes the results of more recent technology development efforts, and describes waste management approaches as they apply to a representative full recycle reprocessing flowsheet. Many of the waste management technologies discussed also apply to other potential flowsheets that involve reprocessing. These applications are occasionally discussed where the data are more readily available. The report summarizes the waste arising from aqueous reprocessing of a typical light-water reactor (LWR) fuel to separate actinides for use in fabricating metal sodium fast reactor (SFR) fuel and from electrochemical reprocessing of the metal SFR fuel to separate actinides for recycle back into the SFR in the form of metal fuel. The primary streams considered and the recommended waste forms include; Tritium in low-water cement in high integrity containers (HICs); Iodine-129: As a reference case, a glass composite material (GCM) formed by the encapsulation of the silver Mordenite (AgZ) getter material in a low-temperature glass is assumed. A number of alternatives with distinct advantages are also considered including a fused silica waste form

  1. Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza. Part I: Influenza life-cycle and currently available drugs.

    PubMed

    Gasparini, R; Amicizia, D; Lai, P L; Bragazzi, N L; Panatto, D

    2014-09-01

    treatment of influenza are considered in the subsequent review.

  2. The Current and Future Treatment of Brain Metastases

    PubMed Central

    Hardesty, Douglas A.; Nakaji, Peter

    2016-01-01

    Brain metastases are the most common intracranial malignancy, accounting for significant morbidity and mortality in oncology patients. The current treatment paradigm for brain metastasis depends on the patient’s overall health status, the primary tumor pathology, and the number and location of brain lesions. Herein, we review the modern management options for these tumors, including surgical resection, radiotherapy, and chemotherapy. Recent operative advances, such as fluorescence, confocal microscopy, and brachytherapy, are highlighted. With an increased understanding of the pathophysiology of brain metastasis come increased future therapeutic options. Therapy targeted to specific tumor molecular pathways, such as those involved in blood–brain barrier transgression, cell–cell adhesion, and angiogenesis, are also reviewed. A personalized plan for each patient, based on molecular characterizations of the tumor that are used to better target radiotherapy and chemotherapy, is undoubtedly the future of brain metastasis treatment. PMID:27252942

  3. The Current and Future Treatment of Brain Metastases.

    PubMed

    Hardesty, Douglas A; Nakaji, Peter

    2016-01-01

    Brain metastases are the most common intracranial malignancy, accounting for significant morbidity and mortality in oncology patients. The current treatment paradigm for brain metastasis depends on the patient's overall health status, the primary tumor pathology, and the number and location of brain lesions. Herein, we review the modern management options for these tumors, including surgical resection, radiotherapy, and chemotherapy. Recent operative advances, such as fluorescence, confocal microscopy, and brachytherapy, are highlighted. With an increased understanding of the pathophysiology of brain metastasis come increased future therapeutic options. Therapy targeted to specific tumor molecular pathways, such as those involved in blood-brain barrier transgression, cell-cell adhesion, and angiogenesis, are also reviewed. A personalized plan for each patient, based on molecular characterizations of the tumor that are used to better target radiotherapy and chemotherapy, is undoubtedly the future of brain metastasis treatment.

  4. The design, results and future development of the National Energy Strategy Environmental Analysis Model (NESEAM)

    SciTech Connect

    Fisher, R.E.; Boyd, G.A. ); Breed, W.S. . Office of Environmental Analysis)

    1991-01-01

    The National Energy Strategy Environmental Model (NESEAM) has been developed to project emissions for the National Energy Strategy (NES). Two scenarios were evaluated for the NES, a Current Policy Base Case and a NES Action Case. The results from the NES Actions Case project much lower emissions than the Current Policy Base Case. Future enhancements to NESEAM will focus on fuel cycle analysis, including future technologies and additional pollutants to model. NESEAM's flexibility will allow it to model other future legislative issues. 7 refs., 4 figs., 2 tabs.

  5. From definition to implementation: a cross-industry perspective of past, current and future MIST strategies.

    PubMed

    Nedderman, Angus N R; Dear, Gordon J; North, Stephanie; Obach, R Scott; Higton, David

    2011-08-01

    The article describes and discusses the evolution of strategies to characterize metabolites in support of safety studies over the last 40 years, as well as future trends. Approaches to derive qualitative and quantitative information on metabolites are described, with a particular focus on the comparison of options to quantify metabolites in the absence of authentic standards. Current strategies to assess metabolite profiles are summarized into four general approaches and compared against a number of key criteria. Potential future strategies are discussed, including the use of clinical samples as the starting point for metabolite investigations, minimizing the need for animal radiolabelled studies and establishing metabolite safety without radiolabelled studies in animals or human.

  6. Selling the Drama: Army Marketing Strategies and the Future of Word-of-Mouth Marketing

    DTIC Science & Technology

    2017-02-16

    Degree in Liberal Studies . SSG Darling is a recent graduate of the 27D4O Senior Leader Course at The Judge Advocate General’s Legal Center and... Strategies and the Future of Word-of-Mouth Marketing Word Count: 2,533 “Selling the Drama”: Army Marketing Strategies and the Future of Word-of-Mouth...be all that you can be” resonated with the public; the copywriter who developed the theme and advertising strategy , “one of the most successful

  7. Childhood Obesity Prevention and Treatment Recommendations for Future Research

    PubMed Central

    Pratt, Charlotte A.; Stevens, June; Daniels, Stephen

    2008-01-01

    This report summarizes the National Heart, Lung, and Blood Institute Working Group’s recommendations on future research directions in childhood obesity prevention and treatment. The Working Group consisted of leaders and representatives from public and private academic and medical institutions with expertise in a variety of health specialties. They reviewed the literature and discussed the findings as well as their own experiences in the prevention and treatment of childhood obesity. The Working Group made recommendations that were based on scientific importance, the potential likelihood of public health impact, and the feasibility and timeliness for childhood obesity prevention and treatment research. These recommendations are intended to assist investigators in the development of research agendas to advance the knowledge of effective childhood obesity prevention and treatment. PMID:18617353

  8. The Future of Prostate Cancer Research and Treatment

    Cancer.gov

    On January 12, 2017 prostate cancer experts William Dahut, M.D. of the National Cancer Institute and Dr. Heather Cheng, M.D. of the University of Washington had a vibrant discussion about current and future research areas and treatment options for prostate cancer. The panel was moderated by Ana Fadich, MPH, CHES Vice President at Men’s Health of the Men's Health Network.

  9. Poor Response to Periodontal Treatment May Predict Future Cardiovascular Disease.

    PubMed

    Holmlund, A; Lampa, E; Lind, L

    2017-07-01

    Periodontal disease has been associated with cardiovascular disease (CVD), but whether the response to the treatment of periodontal disease affects this association has not been investigated in any large prospective study. Periodontal data obtained at baseline and 1 y after treatment were available in 5,297 individuals with remaining teeth who were treated at a specialized clinic for periodontal disease. Poor response to treatment was defined as having >10% sites with probing pocket depth >4 mm deep and bleeding on probing at ≥20% of the sites 1 y after active treatment. Fatal/nonfatal incidence rate of CVD (composite end point of myocardial infarction, stroke, and heart failure) was obtained from the Swedish cause-of-death and hospital discharge registers. Poisson regression analysis was performed to analyze future risk of CVD. During a median follow-up of 16.8 y (89,719 person-years at risk), those individuals who did not respond well to treatment (13.8% of the sample) had an increased incidence of CVD ( n = 870) when compared with responders (23.6 vs. 15.3%, P < 0.001). When adjusting for calendar time, age, sex, educational level, smoking, and baseline values for bleeding on probing, probing pocket depth >4 mm, and number of teeth, the incidence rate ratio for CVD among poor responders was 1.28 (95% CI, 1.07 to 1.53; P = 0.007) as opposed to good responders. The incidence rate ratio among poor responders increased to 1.39 (95% CI, 1.13 to 1.73; P = 0.002) for those with the most remaining teeth. Individuals who did not respond well to periodontal treatment had an increased risk for future CVD, indicating that successful periodontal treatment might influence progression of subclinical CVD.

  10. Treatment-resistant depression: therapeutic trends, challenges, and future directions

    PubMed Central

    Al-Harbi, Khalid Saad

    2012-01-01

    Background Patients with major depression respond to antidepressant treatment, but 10%–30% of them do not improve or show a partial response coupled with functional impairment, poor quality of life, suicide ideation and attempts, self-injurious behavior, and a high relapse rate. The aim of this paper is to review the therapeutic options for treating resistant major depressive disorder, as well as evaluating further therapeutic options. Methods In addition to Google Scholar and Quertle searches, a PubMed search using key words was conducted, and relevant articles published in English peer-reviewed journals (1990–2011) were retrieved. Only those papers that directly addressed treatment options for treatment-resistant depression were retained for extensive review. Results Treatment-resistant depression, a complex clinical problem caused by multiple risk factors, is targeted by integrated therapeutic strategies, which include optimization of medications, a combination of antidepressants, switching of antidepressants, and augmentation with non-antidepressants, psychosocial and cultural therapies, and somatic therapies including electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy, deep brain stimulation, transcranial direct current stimulation, and vagus nerve stimulation. As a corollary, more than a third of patients with treatment-resistant depression tend to achieve remission and the rest continue to suffer from residual symptoms. The latter group of patients needs further study to identify the most effective therapeutic modalities. Newer biomarker-based antidepressants and other drugs, together with non-drug strategies, are on the horizon to address further the multiple complex issues of treatment-resistant depression. Conclusion Treatment-resistant depression continues to challenge mental health care providers, and further relevant research involving newer drugs is warranted to improve the quality of life of patients

  11. Photodynamic therapy for malignant pleural mesothelioma: the future of treatment?

    PubMed

    Friedberg, Joseph S

    2011-02-01

    Malignant pleural mesothelioma is a deadly incurable cancer, with a median survival of approximately 9 months. The best available chemotherapy, arguably the standard of care, only yields a 40% response rate and an 11-week extension in median survival. Surgery, the modality most likely to be associated with prolonged remission, remains investigational and must always be combined with other modalities in an effort to treat the microscopic disease that will remain even after the most aggressive operations. One such modality, photodynamic therapy, is a light-based cancer treatment that has features making it particularly well suited as a component of a surgery-based multimodal treatment plan. Utilizing intraoperative photodynamic therapy has enabled development of a less drastic surgical procedure that is also yielding some encouraging survival results. A unique aspect of photodynamic therapy is its stimulation of a tumor-directed immune response, a feature that offers promise for designing future treatments.

  12. Palmoplantar Psoriasis and Palmoplantar Pustulosis: Current Treatment and Future Prospects.

    PubMed

    Raposo, Inês; Torres, Tiago

    2016-08-01

    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.

  13. Treatment of intracerebral hemorrhage: a selective review and future directions.

    PubMed

    Ganesh Kumar, Nishant; Zuckerman, Scott L; Khan, Imad S; Dewan, Michael C; Morone, Peter J; Mocco, J

    2017-10-01

    Intracerebral hemorrhage (ICH) is a devastating disease. Sixty percent of survivors do not function independently at one year. Treatment of ICH costs approximately US$ 12.7 billion annually. To date no intervention has demonstrated clear efficacy in improving outcomes. The goal of this selective review is to provide an understanding of current treatment and discuss future directions. After a discussion of pathophysiology and societal impact, a synopsis of treatment options is reviewed, including: 1) open craniotomy; 2) catheter-based thrombolytic therapy; 3) endoscopic evacuation; and 4) ultrasonic lysis. Amongst other studies, we will discuss the results of STICH (International Surgical Trial in ICH) and MISTIE (Minimally Invasive Surgery plus Recombinant Tissue-type Plasminogen Activator for ICH Evacuation). We hope to provide a succinct, pragmatic review for the neurosurgical community on the current state of therapy and encourage novel ways to aggressively treat this burdensome disease.

  14. Treatment compliance in chronic illness: Current situation and future perspectives.

    PubMed

    Conthe, P; Márquez Contreras, E; Aliaga Pérez, A; Barragán García, B; Fernández de Cano Martín, M N; González Jurado, M; Ollero Baturone, M; Pinto, J L

    2014-01-01

    Long-term chronic diseases have a high mortality rate around the world, affecting both genders equally. Despite improvements in the diagnosis and treatment of various health problems, lack of treatment compliance remains an obstacle to improving health and patient quality of life, and it carries a high associated socio-healthcare cost. The objectives of this study were to develop the concept of «therapeutic adherence», which includes both pharmacological compliance as well as non-pharmacological (level of agreement and patient involvement, lifestyle changes, etc.) treatments. The study also aimed to establish the clinical and socio-health impact of non-compliance, the reasons for non-compliance, and methods and strategies to improve compliance. The results of this study support therapeutic adherence as an essential goal of the healthcare system that encompasses all stakeholders involved in patient health. Copyright © 2014 Elsevier España, S.L. All rights reserved.

  15. Urothelial carcinoma of the bladder: definition, treatment and future efforts.

    PubMed

    Prasad, Sandip M; Decastro, G Joel; Steinberg, Gary D

    2011-10-11

    The identification of patients with high-risk bladder cancer is important for the timely and appropriate treatment of this lethal disease. The understanding of the natural history of bladder cancer has improved; however, the criteria used to define high-risk disease and the relevant treatment strategies have remained the same for the past several decades, despite multiple large, randomized, prospective clinical trials that have evaluated the use of intravesical, surgical and systemic therapies. The genetic signature of high-risk bladder cancer has been a focus of investigation and has led to the discovery of potential molecular targets for disease identification, risk stratification and therapy. These advances, combined with a comprehensive risk assessment profile that incorporates available pathological and clinical characteristics, might improve the diagnosis and treatment of patients with bladder cancer.

  16. A multi-level strategy for anticipating future glacier lake formation and associated hazard potentials

    NASA Astrophysics Data System (ADS)

    Frey, H.; Haeberli, W.; Linsbauer, A.; Huggel, C.; Paul, F.

    2010-02-01

    In the course of glacier retreat, new glacier lakes can develop. As such lakes can be a source of natural hazards, strategies for predicting future glacier lake formation are important for an early planning of safety measures. In this article, a multi-level strategy for the identification of overdeepened parts of the glacier beds and, hence, sites with potential future lake formation, is presented. At the first two of the four levels of this strategy, glacier bed overdeepenings are estimated qualitatively and over large regions based on a digital elevation model (DEM) and digital glacier outlines. On level 3, more detailed and laborious models are applied for modeling the glacier bed topography over smaller regions; and on level 4, special situations must be investigated in-situ with detailed measurements such as geophysical soundings. The approaches of the strategy are validated using historical data from Trift Glacier, where a lake formed over the past decade. Scenarios of future glacier lakes are shown for the two test regions Aletsch and Bernina in the Swiss Alps. In the Bernina region, potential future lake outbursts are modeled, using a GIS-based hydrological flow routing model. As shown by a corresponding test, the ASTER GDEM and the SRTM DEM are both suitable to be used within the proposed strategy. Application of this strategy in other mountain regions of the world is therefore possible as well.

  17. Genetics, diagnosis, and future treatment strategies for primary ciliary dyskinesia

    PubMed Central

    Daniels, M. Leigh Anne; Noone, Peadar G.

    2015-01-01

    Introduction Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder resulting in chronic oto-sino-pulmonary disease. While PCD is estimated to occur in 1 in 20,000 individuals, fewer than 1,000 patients in the US have a well-established diagnosis. Areas Covered We provide an overview of the clinical manifestations of PCD, describe the evolution of diagnostic methods, and critique the literature on management of PCD. Expert Opinion Although interest in clinical studies in non-CF bronchiectasis has increased in recent years, some of whom enroll patients with PCD, the literature regarding therapy for PCD as a distinct entity is lacking, as the numbers are small, and there have been no sub-analyses published. However, with improved screening and diagnostic methods, the development of clinical and research consortiums, and actively enrolling registries of PCD patients, the environment is conducive to perform longitudinal studies of disease course and therapeutic studies to alter that course. PMID:26998415

  18. Recent and Future Advances in the Treatment of Status Epilepticus

    PubMed Central

    Knake, Susanne

    2008-01-01

    Status epilepticus (SE) is one of the most frequent neurological emergencies with an incidence of 20/100,000 per year and a mortality between 3% and 40% depending on etiology, age, SE type and duration. Generalized convulsive forms of SE (GTCSE), in particular, require aggressive treatment. Presently, only 55–80% of cases of GTCSE are controlled by initial therapy. Therefore, there is a need for new options for the treatment of SE. Here we review the current standard treatment including recent advances and provide a summary of preclinical and clinical data regarding treatment options which may become available in the near future. The initial treatment of SE usually consists of a benzodiazepine (preferably lorazepam 0.1 mg/kg) followed by phenytoin or fosphenytoin or valproic acid (where approved for SE therapy). With intravenous formulations of levetiracetam, available since 2006, and lacosamide, which is expected for autumn of 2008, new treatment options have become available, that should be evaluated in prospective controlled trials. If SE remains refractory, the induction of general anaesthesia using propofol, midazolam, thiopental, or pentobarbital is warranted in GTCSE. PMID:21180563

  19. Emerging strategies for the treatment of gastroparesis.

    PubMed

    Langworthy, James; Parkman, Henry P; Schey, Ron

    2016-07-01

    Gastroparesis is a syndrome of delayed gastric emptying in the absence of mechanical obstruction. Symptoms can be debilitating, affect nutritional states, and significantly impact patients' quality of life. The management of these patients can prove quite difficult to many providers. This article will review the current management recommendations of gastroparesis, discuss investigational medications and interventions, and summarize future directions of therapies targeting the underlying disease process. Current therapies are subdivided into those improving gastric motility and those directly targeting symptoms. Non-pharmacologic interventions, including gastric stimulator implantation and intra-pyloric botulinum toxic injection are reviewed. A discussion of expert opinion in the field, a look into the future of gastroparesis management, and a key point summary conclude the article.

  20. Current treatment and future prospects of dopa-induced dyskinesias.

    PubMed

    Mazzucchi, S; Frosini, D; Bonuccelli, U; Ceravolo, R

    2015-05-01

    Levodopa-induced dyskinesias (LID) are one of the main issues in the management of Parkinson's disease (PD); once these dyskinesias are established treatment becomes difficult, so preventive strategies should be first evaluated. Although levodopa (LD) treatment has recently been related as risk factor for LID, the main strategy to delay LID is to start PD treatment with dopamine agonists, adding LD at low doses. After LID onset, approaches include reducing single LD doses, reducing or discontinuing monoamine oxidase type B/catechol O-methyltransferase (MAO-B/COMT) inhibitors and extended-release (ER) LD. Amantadine represents the best antidyskinetic tool, and ER amantadine is the most promising upcoming antidyskinetic drug. New LD formulations such as IPX-066 (able to provide continuous dopaminergic stimulation) also represent promising new approaches. The involvement of a nondopaminergic system in the pathogenesis of LID suggests that the modulation of glutamate, serotonin and adenosine could have potential as new upcoming drug targets, but the role of such drugs will still need to be confirmed in randomized controlled trials.

  1. Atrial fibrillation: review of current treatment strategies.

    PubMed

    Xu, Joshua; Luc, Jessica G Y; Phan, Kevin

    2016-09-01

    Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in modern clinical practice, with an estimated prevalence of 1.5-2%. The prevalence of AF is expected to double in the next decades, progressing with age and increasingly becoming a global medical challenge. The first-line treatment for AF is often medical treatment with either rate control or anti-arrhythmic agents for rhythm control, in addition to anti-coagulants such as warfarin for stroke prevention in patient at risk. Catheter ablation has emerged as an alternative for AF treatment, which involves myocardial tissue lesions to disrupt the underlying triggers and substrates for AF. Surgical approaches have also been developed for treatment of AF, particularly for patients requiring concomitant cardiac surgery or those refractory to medical and catheter ablation treatments. Since the introduction of the Cox-Maze III, this procedure has evolved into several modern variations, including the use of alternative energy sources (Cox-Maze IV) such as radiofrequency, cryo-energy and microwave, as well as minimally invasive thoracoscopic epicardial approaches. Another recently introduced technique is the hybrid ablation approach, where in a single setting both epicardial thoracoscopic ablation lesions and endocardial catheter ablation lesions are performed by the cardiothoracic surgeon and cardiologist. There remains controversy surrounding the optimal approach for AF ablation, energy sources, and lesion sets employed. The goal of this article is review the history, classifications, pathophysiology and current treatment options for AF.

  2. Dentinogenesis imperfecta: an early treatment strategy.

    PubMed

    Sapir, S; Shapira, J

    2001-01-01

    Dentinogenesis imperfecta (DI) type 2 is a disease inherited in a simple autosomal dominant mode. As soon as the teeth erupt the parents may notice the problem and look for a pediatric dentist's advice and treatment. Early diagnosis and treatment of DI is recommended, as it may prevent or intercept deterioration of the teeth and occlusion and improve esthetics. The purpose of this article is to present the objectives, treatment options, and problems encountered in the treatment of DI in the early primary dentition. A two-stage treatment of a toddler under general anesthesia is described and discussed. This paper recommends for severe cases of DI two treatment stages performed under general anesthesia. Stage 1 is early (around age 18-20 months) and is directed to covering the incisors with composite restorations and the first primary molars with preformed crowns. Stage 2 (around age 28-30 months) seeks to protect the second primary molars with preformed crowns and cover the canines with composite restorations.

  3. Atrial fibrillation: review of current treatment strategies

    PubMed Central

    Xu, Joshua; Luc, Jessica G. Y.

    2016-01-01

    Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in modern clinical practice, with an estimated prevalence of 1.5–2%. The prevalence of AF is expected to double in the next decades, progressing with age and increasingly becoming a global medical challenge. The first-line treatment for AF is often medical treatment with either rate control or anti-arrhythmic agents for rhythm control, in addition to anti-coagulants such as warfarin for stroke prevention in patient at risk. Catheter ablation has emerged as an alternative for AF treatment, which involves myocardial tissue lesions to disrupt the underlying triggers and substrates for AF. Surgical approaches have also been developed for treatment of AF, particularly for patients requiring concomitant cardiac surgery or those refractory to medical and catheter ablation treatments. Since the introduction of the Cox-Maze III, this procedure has evolved into several modern variations, including the use of alternative energy sources (Cox-Maze IV) such as radiofrequency, cryo-energy and microwave, as well as minimally invasive thoracoscopic epicardial approaches. Another recently introduced technique is the hybrid ablation approach, where in a single setting both epicardial thoracoscopic ablation lesions and endocardial catheter ablation lesions are performed by the cardiothoracic surgeon and cardiologist. There remains controversy surrounding the optimal approach for AF ablation, energy sources, and lesion sets employed. The goal of this article is review the history, classifications, pathophysiology and current treatment options for AF. PMID:27747025

  4. Future treatment and research directions in distal radius fracture.

    PubMed

    Jupiter, Jesse

    2012-05-01

    Whether or not they will have their lives dramatically extended in the next few decades, it is clear that people are living longer, healthier, and more active lives. The two peak incidences of distal radius fractures will remain within the pediatric and geriatric age groups, with the latter experiencing a substantial increase in the coming years. This article attempts to project future developments with regard to epidemiology, risk and prevention, fracture assessment, and treatment of distal radius fractures, and the ever increasing concern for the economic impact of this prevalent injury. Copyright © 2012. Published by Elsevier Inc.

  5. Progressive multifocal leukoencephalopathy: current treatment options and future perspectives

    PubMed Central

    Pavlovic, Dejan; Patera, Andriani C.; Nyberg, Fredrik; Gerber, Marianne; Liu, Maggie

    2015-01-01

    Progressive multifocal leukoencephalopathy (PML) is a rare but debilitating and frequently fatal viral disease of the central nervous system, primarily affecting individuals with chronically and severely suppressed immune systems. The disease was relatively obscure until the outbreak of HIV/AIDS, when it presented as one of the more frequent opportunistic infections in this immune deficiency syndrome. It attracted additional attention from the medical and scientific community following the discovery of significant PML risk associated with natalizumab, a monoclonal antibody used for treatment of relapsing–remitting multiple sclerosis. This was followed by association of PML with other immunosuppressive or immunomodulating drugs. PML is currently untreatable disease with poor outcomes, so it is a significant concern when developing new immunotherapies. Current prophylaxis and treatment of PML are focused on immune reconstitution, restoration of immune responses to JC virus infection, and eventual suppression of immune reconstitution inflammatory syndrome. This approach was successful in reducing the incidence of PML and improved survival of PML patients with HIV infection. However, the outcome for the majority of PML patients, regardless of their medical history, is still relatively poor. There is a high unmet need for both prophylaxis and treatment of PML. The aim of this review is to discuss potential drug candidates for prophylaxis and treatment of PML with a critical review of previously conducted and completed PML treatment studies as well as to provide perspectives for future therapies. PMID:26600871

  6. Immunotherapy treatments for small-cell lung cancer: past, present and future

    PubMed Central

    Whitehurst, Matthew; Chiappori, Alberto

    2015-01-01

    Summary Small-cell lung cancer remains a considerable cause of morbidity and mortality. To this day, first-line therapy continues to be a platinum agent with etoposide, combined with radiation therapy in cases of limited stage disease. Numerous, largely unsuccessful, attempts at controlling the disease have included different chemotherapy strategies, the utilization of antiangiogenic agents, tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors and other treatment modalities. Immunotherapy, including vaccines, immune response modifiers, inhibitors of check point blockades and immunologic-targeted toxins may well be the future of treatment, not only to enhance the proven chemotherapy effects, but to improve the control of minimal residual disease and the response with salvage chemotherapy. This article reviews the current advances in immunotherapeutic strategies against small-cell lung cancer. PMID:26236401

  7. Treatment strategies for sarcopenia and frailty.

    PubMed

    Rolland, Yves; Dupuy, Charlotte; Abellan van Kan, Gabor; Gillette, Sophie; Vellas, Bruno

    2011-05-01

    Sarcopenia is the key feature of frailty in older people and a major determinant of adverse health outcomes such as functional limitations and disability. Resistance training and adequate protein and energy intake are the key strategies for the management of sarcopenia. Management of weight loss and resistance training are the most relevant protective countermeasures to slow down the decline of muscle mass and muscle strength. The quality of amino acids in the diet is an important factor for stimulating protein synthesis. Vitamin D deficiency should be treated, and new pharmacologic approaches for sarcopenia are currently assessed.

  8. Nitroimidazoles for the treatment of TB: past, present and future

    PubMed Central

    Mukherjee, Tathagata; Boshoff, Helena

    2011-01-01

    Tuberculosis remains a leading cause of death resulting from an infectious agent, and the spread of multi- and extensively drug-resistant strains of Mycobacterium tuberculosis poses a threat to management of global health. New drugs that effectively shorten the duration of treatment and are active against drug-resistant strains of this pathogen are urgently required to develop effective chemotherapies to combat this disease. Two nitroimidazoles, PA-824 and OPC-67683, are currently in Phase II clinical trials for the treatment of TB and the outcome of these may determine the future directions of drug development for anti-tubercular nitroimidazoles. In this review we summarize the development of these nitroimidazoles and alternative analogs in these series that may offer attractive alternatives to PA-824 and OPC-67683 for further development in the drug-discovery pipeline. Lastly, the potential pitfalls in the development of nitroimidazoles as drugs for TB are discussed. PMID:21879846

  9. Metastatic disease from uveal melanoma: treatment options and future prospects

    PubMed Central

    Carvajal, Richard D; Schwartz, Gary K; Tezel, Tongalp; Marr, Brian; Francis, Jasmine H; Nathan, Paul D

    2017-01-01

    Uveal melanoma represents ∼85% of all ocular melanomas and up to 50% of patients develop metastatic disease. Metastases are most frequently localised to the liver and, as few patients are candidates for potentially curative surgery, this is associated with a poor prognosis. There is currently little published evidence for the optimal management and treatment of metastatic uveal melanoma and the lack of effective therapies in this setting has led to the widespread use of systemic treatments for patients with cutaneous melanoma. Uveal and cutaneous melanomas are intrinsically different diseases and so dedicated management strategies and therapies for uveal melanoma are much needed. This review explores the biology of uveal melanoma and how this relates to ongoing trials of targeted therapies in the metastatic disease setting. In addition, we consider the options to optimise patient management and care. PMID:27574175

  10. Present and Future in the Treatment of Diabetic Kidney Disease

    PubMed Central

    de Arriba, Gabriel

    2015-01-01

    Diabetic kidney disease is the leading cause of end-stage renal disease. Albuminuria is recognized as the most important prognostic factor for chronic kidney disease progression. For this reason, blockade of renin-angiotensin system remains the main recommended strategy, with either angiotensin converting enzyme inhibitors or angiotensin II receptor blockers. However, other antiproteinuric treatments have begun to be studied, such as direct renin inhibitors or aldosterone blockers. Beyond antiproteinuric treatments, other drugs such as pentoxifylline or bardoxolone have yielded conflicting results. Finally, alternative pathogenic pathways are being explored, and emerging therapies including antifibrotic agents, endothelin receptor antagonists, or transcription factors show promising results. The aim of this review is to explain the advances in newer agents to treat diabetic kidney disease, along with the background of the renin-angiotensin system blockade. PMID:25945357

  11. Current treatment for Alzheimer disease and future prospects.

    PubMed

    Tariot, Pierre N; Federoff, Howard J

    2003-01-01

    A cascade of pathophysiological events is triggered in Alzheimer disease (AD) that ultimately involves common cellular signaling pathways and leads to cellular and network dysfunction, failure of neurotransmission, cell death, and a common clinical outcome. The process is asynchronous, meaning that viable neurons remain as targets for therapy even in the diseased state, and each stage of the cascade affords the possibility for therapeutic intervention. Cholinesterase inhibitors are the only available treatment in the United States for patients with mild to moderate AD, helping maintain cognitive and functional abilities in most patients and conferring beneficial behavioral effects in some. Memantine is an NMDA receptor antagonist that has recently been approved in Europe for treatment of moderately severe to severe AD and is under investigation in the United States. Its mechanism of action may include enhanced neurotransmission in several systems as well as antiexcitotoxic effects. There are data regarding the effectiveness of the combination of memantine with cholinesterase inhibitors that will be useful for the practicing clinician. Other agents have shown some benefit in clinical trials, including the antioxidants vitamin E, selegiline, and Ginkgo biloba extracts, although the weight of evidence regarding their effects is not sufficient to define clinical practice. Potential future therapies currently are in development that target multiple aspects of the illness cascade, including aberrant inflammation, neurotrophic function, and processing of beta amyloid and tau proteins. These newer approaches hold promise for disease modification but are as yet unproven. Whether or not disease-modifying or preventive therapies become a reality, clinicians will be faced with AD patients who require treatment at all stages of illness for the indefinite future. Cholinergic and emerging noncholinergic medications will likely prevail as the standards of treatment for years to

  12. Gastric ESD may be useful as accurate staging and decision of future therapeutic strategy

    PubMed Central

    Fujimoto, Ai; Goto, Osamu; Nishizawa, Toshihiro; Ochiai, Yasutoshi; Horii, Joichiro; Maehata, Tadateru; Akimoto, Teppei; Kinoshita, Satoshi; Sagara, Seiji; Sasaki, Motoki; Uraoka, Toshio; Yahagi, Naohisa

    2017-01-01

    Background and study aims We sometimes perform gastric endoscopic submucosal dissection (ESD) for total pathologic diagnosis when preoperative diagnosis is difficult. In the present study we analyzed the treatment outcomes and adverse events of diagnostic ESD for early gastric cancer (EGC). Patients and methods We conducted a retrospective analysis of 18 consecutive cases of EGC in 18 patients with a suspected out-of-indication diagnosis who underwent diagnostic ESD, between June 2010 and November 2014. The following parameters were examined: the average length of the longer axis of the lesion; the procedure time; the rates of en bloc resection (ER), complete en bloc resection (CER), and curative resection (CR) as treatment outcomes; and the rates of perforation, delayed bleeding, aspiration pneumonia, disease-related death, and emergency surgery as adverse events. Results The treatment outcomes were as follows: average length of the longer axis of the lesion, 27.4 ± 10.0 mm; procedure time, 87.0 ± 43.1 minutes; ER rate, 18/18 (100.0 %); CER rate, 13/18 (72.2 %); CR rate, 4/18 (22.2 %). CR rate was achieved 37.5 % for the lesions which preoperative diagnosis was more than 30 mm (> 30 mm) in diameter differentiated type with mucosal layer/submucosal layer 1 invasion and ulceration positive. The adverse events (AEs) were perforation in 1 of 18 (5.5 %) patients and delayed bleeding in 1 of 18 (5.5 %). There were no other AEs. Conclusions Diagnostic ESD may be acceptable for future therapeutic strategy when we unconfirmed the pre ESD diagnosis because of lower rate of adverse events and high rate of ER. PMID:28210705

  13. Platinum-induced neurotoxicity and preventive strategies: past, present, and future.

    PubMed

    Avan, Abolfazl; Postma, Tjeerd J; Ceresa, Cecilia; Avan, Amir; Cavaletti, Guido; Giovannetti, Elisa; Peters, Godefridus J

    2015-04-01

    models and appropriate trials planning should be integrated into the future design of neuroprotective strategies to find the best patient-oriented solution. ©AlphaMed Press.

  14. Platinum-Induced Neurotoxicity and Preventive Strategies: Past, Present, and Future

    PubMed Central

    Avan, Abolfazl; Postma, Tjeerd J.; Ceresa, Cecilia; Avan, Amir; Cavaletti, Guido; Giovannetti, Elisa

    2015-01-01

    models and appropriate trials planning should be integrated into the future design of neuroprotective strategies to find the best patient-oriented solution. PMID:25765877

  15. Emerging strategies for the treatment of retinoblastoma.

    PubMed

    Deegan, William F

    2003-10-01

    Over the past 10 years, the treatment of retinoblastoma has changed dramatically. The main impetus for these changes, which are more intensive than traditional modalities and require a multidisciplinary approach, has been the avoidance of the serious, often fatal, complications of external beam radiation. The use of potent, well known chemotherapy agents in a novel setting (ie, intraocular tumor) has been successful in treating all but the most advanced disease. This review will examine recent published work with chemotherapy and local (focal laser) treatment for intraocular (curable) retinoblastoma. Specifically, the concepts behind and the practice of chemoreduction and thermochemotherapy and their efficacies will be evaluated. The work discussed herein constitutes an extremely nascent and dynamic field of work in ocular oncology. Much uncertainty remains, especially as most of these patients will live for many decades after their presentation and treatment. The review will show that a significant number of treatment failures still occur and that continued work is needed before we can feel confident treating young patients with all forms of this rare tumor.

  16. Treatment strategies for tics in Tourette syndrome.

    PubMed

    Eddy, Clare M; Rickards, Hugh E; Cavanna, Andrea E

    2011-01-01

    TOURETTE SYNDROME (TS) IS A CHRONIC NEURODEVELOPMENTAL DISORDER CHARACTERIZED BY TICS: repetitive, involuntary movements and vocalizations. These symptoms can have a significant impact on patients' daily functioning across many domains. Tics tend to be most severe in child and adolescent sufferers, so their presence has the potential to impact a period of life that is both critical for learning and is often associated with the experience of greater social tension and self-consciousness than adulthood. Furthermore, control over tics that lead to physical impairment or self-injurious behaviour is of vital importance in maintaining health and quality of life. There are numerous complicating factors in the prescription of treatment for tics, due to both the side effects associated with alleviating agents and patient characteristics, such as age and comorbid conditions. This review summarizes literature pertaining to the efficacy and safety of both traditionally prescribed and more modern medications. We also discuss the merits of behavioural and surgical techniques and highlight newer emerging treatments. Although treatment response is to some extent variable, there are a number of agents that are clearly useful as first-line treatments for TS. Other interventions may be of most benefit to patients exhibiting refractory tics or more specific symptom profiles.

  17. Forest treatment strategies for Phytophthora ramorum

    Treesearch

    Yana Valachovic; Chris Lee; Jack Marshall; Hugh. Scanlon

    2010-01-01

    Although there is no known cure or preventative on a landscape scale for sudden oak death (SOD), the plant disease caused by Phytophthora ramorum, a variety of management options has been tested with the goal of developing an integrated program of treatment for the pathogen. This paper presents a first attempt to gather together individual...

  18. Treatment strategies for tics in Tourette syndrome

    PubMed Central

    Eddy, Clare M.; Rickards, Hugh E.; Cavanna, Andrea E.

    2011-01-01

    Tourette syndrome (TS) is a chronic neurodevelopmental disorder characterized by tics: repetitive, involuntary movements and vocalizations. These symptoms can have a significant impact on patients’ daily functioning across many domains. Tics tend to be most severe in child and adolescent sufferers, so their presence has the potential to impact a period of life that is both critical for learning and is often associated with the experience of greater social tension and self-consciousness than adulthood. Furthermore, control over tics that lead to physical impairment or self-injurious behaviour is of vital importance in maintaining health and quality of life. There are numerous complicating factors in the prescription of treatment for tics, due to both the side effects associated with alleviating agents and patient characteristics, such as age and comorbid conditions. This review summarizes literature pertaining to the efficacy and safety of both traditionally prescribed and more modern medications. We also discuss the merits of behavioural and surgical techniques and highlight newer emerging treatments. Although treatment response is to some extent variable, there are a number of agents that are clearly useful as first-line treatments for TS. Other interventions may be of most benefit to patients exhibiting refractory tics or more specific symptom profiles. PMID:21339906

  19. SECONDARY WASTE MANAGEMENT STRATEGY FOR EARLY LOW ACTIVITY WASTE TREATMENT

    SciTech Connect

    TW, CRAWFORD

    2008-07-17

    This study evaluates parameters relevant to River Protection Project secondary waste streams generated during Early Low Activity Waste operations and recommends a strategy for secondary waste management that considers groundwater impact, cost, and programmatic risk. The recommended strategy for managing River Protection Project secondary waste is focused on improvements in the Effiuent Treatment Facility. Baseline plans to build a Solidification Treatment Unit adjacent to Effluent Treatment Facility should be enhanced to improve solid waste performance and mitigate corrosion of tanks and piping supporting the Effiuent Treatment Facility evaporator. This approach provides a life-cycle benefit to solid waste performance and reduction of groundwater contaminants.

  20. Acute behavioral interventions and outpatient treatment strategies with suicidal adolescents

    PubMed Central

    O’Brien, Kimberly H. McManama; Singer, Jonathan B.; LeCloux, Mary; Duarté-Vélez, Yovanska; Spirito, Anthony

    2015-01-01

    Despite the prevalence of suicidal thoughts and behaviors among adolescents, there is limited knowledge of effective interventions to use with this population. This paper reviews the findings of studies on behavioral interventions for adolescents who are at acute suicide risk, as well as outpatient treatment and risk management strategies with suicidal adolescents. The importance of addressing comorbid behaviors and enhancing protective factors are discussed. Cultural considerations in working with suicidal adolescents and strategies for conducting culturally competent treatment are explored. PMID:26279646

  1. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies

    PubMed Central

    Li, Guihong; Yu, Fengbo; Lei, Ting; Gao, Haijun; Li, Peiwen; Sun, Yuxue; Huang, Haiyan; Mu, Qingchun

    2016-01-01

    Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research. PMID:27482235

  2. Treatment strategies in mantle cell lymphoma.

    PubMed

    Maddocks, Kami; Blum, Kristie A

    2015-01-01

    Mantle cell lymphoma (MCL) is a distinct B-cell non-Hodgkin's lymphoma (NHL) defined by the translocation t(11;14). MCL combines characteristics of both indolent and aggressive lymphomas, and it is incurable with conventional chemoimmunotherapy but has a more aggressive disease course. Minimal data exist on treatment of patients diagnosed with early-stage disease (stage I-II non-bulky), as this represents only a small portion of the patients diagnosed with MCL, but therapeutic options evaluated in retrospective studies include radiation or combination radiation and chemotherapy. There is a subset of patients with newly diagnosed MCL that can be observed without treatment, but the majority of patients will require treatment at diagnosis. Treatment is often based on age (≤65-70 years of age), comorbidities, and risk factors for disease. The majority of patients who are younger and without significant comorbidities are treated with intensive induction using combination chemoimmunotherapy regimens, many which include consolidation with autologous stem cell transplant (ASCT). Several regimens have been studied that show improved median progression-free survival (PFS) to 3-6 years in this population of patients. The majority of older patients (≥65-70 years of age) are treated with combination chemoimmunotherapy regimens with consideration of rituximab maintenance, with enrollment on a clinical trial encouraged. Therapy for relapsed disease is dependent on prior treatment, age, comorbidities, and toxicities but includes targeted therapies such as the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, the immunomodulatory agent lenalidomide, the proteasome inhibitor bortezomib, combination chemoimmunotherapy, ASCT, and allogeneic stem cell transplant in selected cases. Several novel agents and targeted therapies alone or in combination are currently being studied and developed in both the upfront and relapsed setting.

  3. Schistosomiasis: Drugs used and treatment strategies.

    PubMed

    Siqueira, Lidiany da Paixão; Fontes, Danilo Augusto Ferreira; Aguilera, Cindy Siqueira Britto; Timóteo, Taysa Renata Ribeiro; Ângelos, Matheus Alves; Silva, Laysa Creusa Paes Barreto Barros; de Melo, Camila Gomes; Rolim, Larissa Araújo; da Silva, Rosali Maria Ferreira; Neto, Pedro José Rolim

    2017-08-10

    Neglected tropical diseases (NTDs) affect millions of people in different geographic regions, especially the poorest and most vulnerable. Currently NTDs are prevalent in 149 countries, seventeen of these neglected tropical parasitic diseases are classified as endemic. One of the most important of these diseases is schistosomiasis, also known as bilharzia, a disease caused by the genus Schistosoma. It presents several species, such as Schistosoma haematobium, Schistosoma japonicum and Schistosoma mansoni, the latter being responsible for parasitosis in Brazil. Contamination occurs through exposure to contaminated water in the endemic region. This parasitosis is characterized by being initially asymptomatic, but it is able to evolve into more severe clinical forms, potentially causing death. Globally, more than 200 million people are infected with one of three Schistosome species, including an estimated 40 million women of reproductive age. In Brazil, about 12 million children require preventive chemotherapy with anthelmintic. However, according to the World Health Organization (WHO), only about 15% of the at-risk children receive regular treatment. The lack of investment by the pharmaceutical industry for the development and/or improvement of new pharmaceutical forms, mainly aimed at the pediatric public, is a great challenge. Currently, the main forms of treatment used for schistosomiasis are praziquantel (PZQ) and oxaminiquine (OXA). PZQ is the drug of choice because it presents as a high-spectrum anthelmintic, used in the treatment of all known species of schistosomiasis and some species of cestodes and trematodes. OXA, however, is not active against the three Schistosome species. This work presents a literature review regarding schistosomiasis. It addresses points such as available treatments, the role of the pharmaceutical industry against neglected diseases, and perspectives for treatment. Copyright © 2017. Published by Elsevier B.V.

  4. Present and future DNA vaccines for chronic hepatitis B treatment.

    PubMed

    Cova, Lucyna

    2017-02-01

    With at least 240 million hepatitis B virus (HBV) carriers worldwide, being at a high risk of cirrhosis and hepatocellular carcinoma (HCC), chronic hepatitis B remains a major public health issue. Because current antiviral treatments are only virostatic, there is an urgent need for the development of innovative anti-HBV strategies leading to the functional cure. In this context, DNA-based vaccines appear as a promising approach. Area covered: In this review, the authors summarize the pertinent features of DNA vaccines for chronic hepatitis B therapy. They review several technologies that improve DNA vaccines efficacy evaluated in animal models of hepadnaviral infection. They also discuss the clinical trials of therapeutic DNA vaccination initiated in HBV-carrier patients. Expert opinion: Preclinical studies in HBV transgenic mice, DHBV-carrier ducks and WHV-infected woodchucks, have clearly demonstrated a benefit of DNA vaccine-based combination therapies for chronic hepatitis B treatment. However, the results of clinical trials conducted in HBV patients were rather disappointing and frustrating, as DNA-vaccines have not shown the same efficacy in patients as in animal models. We are convinced that the design of innovative clinical trials based on strategies able to increase DNA vaccine immunogenicity will allow to advance in this challenging field.

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

    PubMed Central

    Digklia, Antonia; Wagner, Anna Dorothea

    2016-01-01

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

  6. Migraine: a review and future directions for treatment.

    PubMed

    Linde, M

    2006-08-01

    Migraine is a chronic, neurological disorder generally manifesting itself in attacks with severe headache, nausea and an increased reactivity to sensory stimuli. A low migraine threshold is set by genetic factors, although the phenotype also modulates the manifestations. The 1-year prevalence is approximately 13% and is higher among women. Patients usually experience neuropsychological dysfunction, and sometimes also reversible focal neurological symptoms. The trajectories of the characteristic symptoms of acute migraine usually follow a similar time course, indicating a reciprocal underlying mechanism. A central nervous system hyperexcitability has been demonstrated in neurophysiological studies. The dibilitating effects of migraine are not confined to the attacks per se. Many individuals do not recover completely between the attacks and most report a negative impact on the most important life domains, and an interest in testing other treatments. Young persons have a higher frequency of attacks. Acute treatment should routinely be initiated with an analgesic plus a prokinetic anti-emetic. Triptans must not be provided early during the attack to ensure their efficacy. The natural course of attacks is commonly only temporarily altered by acute treatment. Non-pharmacological treatment and drugs may be equally viable in prophylaxis for migraine. In more complicated cases, conjoint therapy should be considered. New strategies to improve adherence with existing therapeutic regimens might yield greater benefits than will new pharmacological agents.

  7. The philosophy of treatment of uveitis: past, present and future.

    PubMed

    Kruh, Jonathan; Foster, C Stephen

    2012-01-01

    Treatment of inflammatory diseases of the eye is especially challenging. Although physicians in antiquity had recognized the existence of ocular inflammatory disease, their lack of understanding of the immune system made successful treatment almost impossible. Throughout the 20th century, great advances in the diagnosis and treatment of uveitis led to unique treatment options. The development of corticosteroids in 1949 and its application to the eye in 1950 revolutionized therapeutic strategies. As the use of corticosteroids became more prevalent in treating ocular inflammatory diseases, so did its side effects. Due to the high morbidity in conjunction with long-term corticosteroid use, physicians pursued other agents, specifically through the employment of chemotherapeutic agents. The shift from exclusive corticosteroid monotherapy to steroid-sparing immunomodulatory therapy reshaped the landscape of treating ocular inflammatory disease. Over time, with increased efforts, new therapies were studied, trialed, and brought to the market. Today, in comparison to any other time in history, physicians have available to them the largest array of effective agents for achieving the ultimate goal: corticosteroid-free, durable remission. Copyright © 2012 S. Karger AG, Basel.

  8. Metabolic syndrome: contributing factors and treatment strategies.

    PubMed

    Fowler, Susan B; Moussouttas, Michael; Mancini, Barbara

    2005-08-01

    Metabolic syndrome is associated with increased risk for cardiovascular and cerebrovascular disease. The World Health Organization and National Cholesterol Education Program Adult Treatment Panel III have identified physiologic abnormalities associated with metabolic syndrome, including impaired glucose metabolism, high blood pressure, elevated cholesterol levels, and abdominal obesity. It is estimated that 47 million Americans have metabolic syndrome. A variety of therapies may help reduce the incidence and risk, including diet, weight loss, physical exercise, glycemic control, and pharmacological treatments. Nursing care is focused on developing an individualized plan of care that includes family members and providing education, psychosocial support, close monitoring, and continued follow-up to ensure adherence and success in achieving patient outcomes.

  9. Weight loss strategies for treatment of obesity.

    PubMed

    Kushner, Robert F

    2014-01-01

    Obesity is one of the most serious and prevalent non-communicable diseases of the 21st century. It is also a patient-centered condition in which affected individuals seek treatment through a variety of commercial, medical and surgical approaches. Considering obesity as a chronic medical disease state helps to frame the concept of using a three-stepped intensification of care approach to weight management. As a foundation, all patients should be counseled on evidence-based lifestyle approaches that include diet, physical activity and behavior change therapies. At the second tier, two new pharmacological agents, phentermine-topiramate and lorcaserin, were approved in 2012 as adjuncts to lifestyle modification. The third step, bariatric surgery, has been demonstrated to be the most effective and long-term treatment for individuals with severe obesity or moderate obesity complicated by comorbid conditions that is not responsive to non-surgical approaches. By using a medical model, clinicians can provide more proactive and effective treatments in assisting their patients with weight loss.

  10. The Future of School Integration: Socioeconomic Diversity as an Education Reform Strategy

    ERIC Educational Resources Information Center

    Kahlenberg, Richard D., Ed.

    2012-01-01

    The Century Foundation released The Future of School Integration: Socioeconomic Diversity as an Education Reform Strategy, edited by senior fellow Richard D. Kahlenberg. The volume seeks to answer important questions about how socioeconomic integration plans are faring and to provide guidance for how they can be sustained and expanded in the…

  11. The Future of School Integration: Socioeconomic Diversity as an Education Reform Strategy

    ERIC Educational Resources Information Center

    Kahlenberg, Richard D., Ed.

    2012-01-01

    The Century Foundation released The Future of School Integration: Socioeconomic Diversity as an Education Reform Strategy, edited by senior fellow Richard D. Kahlenberg. The volume seeks to answer important questions about how socioeconomic integration plans are faring and to provide guidance for how they can be sustained and expanded in the…

  12. What the future holds for ectodermal dysplasias: future research and treatment directions.

    PubMed

    Slavkin, Harold C

    2009-09-01

    A contrarian view suggests that the ectodermal dysplasias, including more than 200 different disorders, represent clinical variability and molecular heterogeneity as well as complex multigene heritable conditions often characterized by dysmorphogenesis of derivatives of embryonic ectoderm and beyond. Controversy exists over which syndromes do or do not belong in the classification of the clinical features that characterize ectodermal dysplasias. For example, Ellis-van Creveld syndrome is characterized by abnormalities of the teeth and hair, as well as of the skeleton and the cardiovascular system. Precision in diagnosis often is a preamble for improved patient diagnosis, treatment and desired outcomes. In tandem, molecular studies of complex epithelial-mesenchymal interactions required for ectodermal derivatives (e.g., hair, nail, skin, teeth, and exocrine glands) continue to identify and explain many signal transduction pathways and networks related to ectodermal dysplasias. Meanwhile, major international investments in fundamental biomedical research continue to yield significant benefits to the larger society. The convergence of informatics, nanotechnology, genomics, and epigenetic studies with clinical medicine and dentistry promise major progress for special needs patients such as ectodermal dysplasias. For example, investments in the molecular biology of genes and their regulation and function now provide more than 30 candidates for specific biomarkers to improve diagnosis, prognosis, treatments, therapeutics, and biomaterials for ectodermal dysplasias. Innovations in high throughput genotyping, gene mapping, single nucleotide polymorphisms (SNPs), interference RNA treatments, bioimaging, tissue engineering and related biomimetic approaches to design and fabricate biomaterials, offer enormous promise for the future of ectodermal dysplasias.

  13. Tooth surface treatment strategies for adhesive cementation.

    PubMed

    Rohr, Nadja; Fischer, Jens

    2017-04-01

    The aim of this study was to evaluate the effect of tooth surface pre-treatment steps on shear bond strength, which is essential for understanding the adhesive cementation process. Shear bond strengths of different cements with various tooth surface treatments (none, etching, priming, or etching and priming) on enamel and dentin of human teeth were measured using the Swiss shear test design. Three adhesives (Permaflo DC, Panavia F 2.0, and Panavia V5) and one self-adhesive cement (Panavia SA plus) were included in this study. The interface of the cement and the tooth surface with the different pre-treatments was analyzed using SEM. pH values of the cements and primers were measured. The highest bond strength values for all cements were achieved with etching and primer on enamel (25.6 ± 5.3 - 32.3 ± 10.4 MPa). On dentin, etching and priming produced the highest bond strength values for all cements (8.6 ± 2.9 - 11.7 ± 3.5 MPa) except for Panavia V5, which achieved significantly higher bond strengths when pre-treated with primer only (15.3 ± 4.1 MPa). Shear bond strength values were correlated with the micro-retentive surface topography of enamel and the tag length on dentin except for Panavia V5, which revealed the highest bond strength with primer application only without etching, resulting in short but sturdy tags. The highest bond strength can be achieved for Panavia F 2.0, Permaflo DC, and Panavia SA plus when the tooth substrate is previously etched and the respective primer is applied. The new cement Panavia V5 displayed low technique-sensitivity and attained significantly higher adhesion of all tested cements to dentin when only primer was applied.

  14. Tooth surface treatment strategies for adhesive cementation

    PubMed Central

    2017-01-01

    PURPOSE The aim of this study was to evaluate the effect of tooth surface pre-treatment steps on shear bond strength, which is essential for understanding the adhesive cementation process. MATERIALS AND METHODS Shear bond strengths of different cements with various tooth surface treatments (none, etching, priming, or etching and priming) on enamel and dentin of human teeth were measured using the Swiss shear test design. Three adhesives (Permaflo DC, Panavia F 2.0, and Panavia V5) and one self-adhesive cement (Panavia SA plus) were included in this study. The interface of the cement and the tooth surface with the different pre-treatments was analyzed using SEM. pH values of the cements and primers were measured. RESULTS The highest bond strength values for all cements were achieved with etching and primer on enamel (25.6 ± 5.3 - 32.3 ± 10.4 MPa). On dentin, etching and priming produced the highest bond strength values for all cements (8.6 ± 2.9 - 11.7 ± 3.5 MPa) except for Panavia V5, which achieved significantly higher bond strengths when pre-treated with primer only (15.3 ± 4.1 MPa). Shear bond strength values were correlated with the micro-retentive surface topography of enamel and the tag length on dentin except for Panavia V5, which revealed the highest bond strength with primer application only without etching, resulting in short but sturdy tags. CONCLUSION The highest bond strength can be achieved for Panavia F 2.0, Permaflo DC, and Panavia SA plus when the tooth substrate is previously etched and the respective primer is applied. The new cement Panavia V5 displayed low technique-sensitivity and attained significantly higher adhesion of all tested cements to dentin when only primer was applied. PMID:28435616

  15. Adjuvant treatment strategies for early colon cancer.

    PubMed

    Waterston, Ashita M; Cassidy, Jim

    2005-01-01

    Colon cancer remains a major cause of death; however, in the last 3 years a number of trials have been published that have led to changes in the treatment of patients with this disease. Initially, the adjuvant treatment of patients following curative resection was based on their Dukes staging; this is now being refined by consideration of other pathological factors, as well as the investigation of newer prognostic markers such as p53, Ki67 and a number of genes on chromosome 18. Tumours generally develop from the progressive accumulation of genetic events, although some develop through mutation or inactivation of DNA mismatch repair proteins leading to microsatellite instability; this is particularly important in Lynch's syndrome. The loss of gene expression can occur by deletion or mutation of genes or by aberrant methylation of CpG islands. In patients with Dukes C colon cancer the standard of care for adjuvant chemotherapy was previously based on bolus fluorouracil (5-fluorouracil) and folinic acid (leucovorin) administered 5 days per month or weekly for 6 months. Recent studies with a combination of infusional fluorouracil, folinic acid and oxaliplatin have been found to be superior. A further study replacing fluorouracil with oral capecitabine has also demonstrated equivalent disease-free survival. Although some debate remains regarding the benefit of adjuvant treatment for patients with Dukes B colon cancer, the emerging consensus is that, for those patients who are younger and have high-risk features, chemotherapy should be discussed. A number of large vaccine trials have also been conducted in the adjuvant setting and, overall, these have been disappointing. This is a rapidly advancing area of therapy and the results of new trials are awaited to determine whether additional benefits can be achieved with biological therapies such as anti-vascular endothelial growth factor and anti-epithelial growth factor receptor monoclonal antibodies, which have already

  16. [Phantom limb pain. Psychological treatment strategies].

    PubMed

    Diers, M; Flor, H

    2013-04-01

    Similar to other pain syndromes phantom limb pain is characterized by learning and memory processes that maintain the pain and increase maladaptive plastic changes of the brain: therefore, psychological interventions that change maladaptive memory processes are useful. In addition to traditional psychological interventions, such as pain management training and biofeedback, more recent developments that involve sensory discrimination training, mirror treatment, graded motor imagery, prosthesis training and training in virtual reality are interesting. These interventions not only reduce phantom limb pain but also reverse the associated maladaptive brain changes.

  17. [Diagnosis and Treatment of Peptic Ulcer Disease: Present and Future Perspective].

    PubMed

    Kim, Byung Wook

    2016-06-25

    Peptic ulcer disease is one of the most commonly encountered diseases in gastroenterology clinics. After the discovery of Helicobacter pylori by Warren and Marshall, it has been identified as the most important cause of peptic ulcer. Eradication of H. pylori markedly reduces the post-treatment recurrence rate of peptic ulcer. However, as human populations age, the incidence of cardiovascular and musculoskeletal diseases increases and consequent use of aspirin and non-steroidal anti-in-flammatory drugs increases. Thus causes and presenting patterns of peptic ulcer have changed. In this review, I describe new diagnostic and therapeutic strategies for peptic ulcer disease and explore future perspectives.

  18. Nanotechnology-based water treatment strategies.

    PubMed

    Kumar, Sandeep; Ahlawat, Wandit; Bhanjana, Gaurav; Heydarifard, Solmaz; Nazhad, Mousa M; Dilbaghi, Neeraj

    2014-02-01

    The most important component for living beings on the earth is access to clean and safe drinking water. Globally, water scarcity is pervasive even in water-rich areas as immense pressure has been created by the burgeoning human population, industrialization, civilization, environmental changes and agricultural activities. The problem of access to safe water is inevitable and requires tremendous research to devise new, cheaper technologies for purification of water, while taking into account energy requirements and environmental impact. This review highlights nanotechnology-based water treatment technologies being developed and used to improve desalination of sea and brackish water, safe reuse of wastewater, disinfection and decontamination of water, i.e., biosorption and nanoadsorption for contaminant removal, nanophotocatalysis for chemical degradation of contaminants, nanosensors for contaminant detection, different membrane technologies including reverse osmosis, nanofiltration, ultrafiltration, electro-dialysis etc. This review also deals with the fate and transport of engineered nanomaterials in water and wastewater treatment systems along with the risks associated with nanomaterials.

  19. Phenylketonuria: a review of current and future treatments

    PubMed Central

    Al Hafid, Naz

    2015-01-01

    Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism caused by a deficiency in the hepatic enzyme phenylalanine hydroxylase (PAH). If left untreated, the main clinical feature is intellectual disability. Treatment, which includes a low Phe diet supplemented with amino acid formulas, commences soon after diagnosis within the first weeks of life. Although dietary treatment has been successful in preventing intellectual disability in early treated PKU patients, there are major issues with dietary compliance due to palatability of the diet. Other potential issues associated with dietary therapy include nutritional deficiencies especially vitamin D and B12. Suboptimal outcomes in cognitive and executive functioning have been reported in patients who adhere poorly to dietary therapy. There have been continuous attempts at improving the quality of medical foods including their palatability. Advances in dietary therapy such as the use of large neutral amino acids (LNAA) and glycomacropeptides (GMP; found within the whey fraction of bovine milk) have been explored. Gene therapy and enzyme replacement or substitution therapy have yielded more promising data in the recent years. In this review the current and possible future treatments for PKU are discussed. PMID:26835392

  20. Present and future treatment possibilities in macular degeneration

    NASA Astrophysics Data System (ADS)

    Fisher, E.; Wegner, A.; Pfeiler, T.; Mertz, M.

    2005-11-01

    Purpose: To discuss present and future treatment possibilities in different types of choroidal neovascularisation. Methods: Presented are angiographic- and OCT-findings in patients with macular degeneration of different origin. Choroidal neovascularisations, which are not likely to respond positively to established procedures like thermal laser coagulation or photodynamic therapy will be discussed. Results and conclusions: Present study-guidelines and new methods of pharmacological intervention are analysed in different patterns of macular degeneration. Conventional laser coagulation in the treatment of classic, extrafoveal CNV and photodynamic therapy of predominantly classic subfoveal CNV still represent a gold standard. There are new recommendations, loosening the tight criteria of the TAP and VIP-guidelines, which cover, for instance, wider visual acuity ranges and the treatment of juxtafoveally located choroidal neovascularisations. Positive findings in literature confirm the role of PDT in pathologic myopia and other non-AMD CNV. Studies about surgical procedures, like macula- or RPE-translocation after surgical removal or thermal laser destruction of the CNV are in progress and are expected to show promising results. Phase II/III studies will soon point out the effect of anti-VEGF agents. The application of intravitreal (triamcinolone) or peribulbar (anecortave acetat) steroids could be useful. The combination with surgical or laser techniques could bring further benefit to the patient.

  1. Spinal muscular atrophy: diagnosis, treatment and future prospects.

    PubMed

    Baioni, Mariana T C; Ambiel, Celia R

    2010-01-01

    To report on recent genetic and molecular discoveries and on future prospects for the treatment of spinal muscular atrophy (SMA), thereby helping healthcare professionals to make a quick diagnosis and provide appropriate and timely therapeutic support. Information was collected from scientific articles published in the last 2 decades, retrieved from the databases SciELO, PubMed, and MEDLINE. SMA is a neurodegenerative disorder with autosomal recessive genetic heredity. It is caused by a homozygous deletion of the survival motor neuron (SMN1) gene. This genetic alteration results in reduced levels of the SMN protein, leading to degeneration of alpha motor neurons of the spinal cord and resulting in muscle weakness and progressive symmetrical proximal paralysis. It is known that basic nutritional and respiratory care and physiotherapy can be important to delaying disease progression and prolonging patients' lives. Several drugs are being tested, some new, others, such as valproic acid, already known; paralysis can be halted, but not reversed. SMA is a difficult to diagnose disorder, because it is little known, and treatment is uncertain. Pharmacological treatments and supportive therapies are not yet able to recover motor neurons or muscle cells that have already been lost, but are aimed at delaying disease progression and improving patients' residual muscle function, as well as offering better quality of life and life expectancy.

  2. The multimodal treatment of acromegaly: current status and future perspectives.

    PubMed

    Espinosa, Etual; Ramirez, Claudia; Mercado, Moises

    2014-01-01

    Acromegaly is a chronic systemic disorder caused by a GH-secreting pituitary adenoma. Active acromegaly results in a poor quality of life due to symptoms such as headache, fatigue, arthralgia, depression, sexual dysfunction and hyperhidrosis; an increased prevalence of co-morbidities like diabetes, hypertension as well as cancer risk and a reduced life expectancy. Appropriate, modern, multimodal treatment of acromegaly has led to a significant improvement in quality of life, an adequate control of co-morbidities and a drastic reduction in the mortality rates that used to prevail in the past. This multimodal strategy includes an adequate selection of patients who are likely to benefit from surgical treatment (which has to be performed by a skilled pituitary neurosurgeon), the use of pharmacological interventions such as somatostatin analogs and dopamine agonists, which target the pituitary adenoma; and pegvisomant, a GH mutant acting as a competitive antagonist of the GH receptor. Radiation therapy is an important tool, particularly in parts of the World where resources are limited. The ultimate outcome of the individual patient depends on the judicious use of all these treatment options, which are critically analyzed in this mini-review.

  3. Strategies for Prevention and Treatment of Trichomonas vaginalis Infections.

    PubMed

    Bouchemal, Kawthar; Bories, Christian; Loiseau, Philippe M

    2017-07-01

    The last estimated annual incidence of Trichomonas vaginalis worldwide exceeds that of chlamydia and gonorrhea combined. This critical review updates the state of the art on advances in T. vaginalis diagnostics and strategies for treatment and prevention of trichomoniasis. In particular, new data on treatment outcomes for topical administration of formulations are reviewed and discussed. Copyright © 2017 American Society for Microbiology.

  4. Cutaneous porphyrias part II: treatment strategies.

    PubMed

    Tintle, Suzanne; Alikhan, Ali; Horner, Mary E; Hand, Jennifer L; Davis, Dawn Marie R

    2014-01-01

    The porphyrias are diverse in pathophysiology, clinical presentation, severity, and prognosis, presenting a diagnostic and therapeutic challenge. Although not easily curable, the dermatological manifestations of these diseases, photosensitivity and associated cutaneous pathology, can be effectively prevented and managed. Sun avoidance is essential, and patient education regarding the irreversibility of photocutaneous damage is a necessary corollary. Beyond preventative measures, the care of fragile, vulnerable skin, and pain management, each of the porphyrias has a limited number of unique additional therapeutic options. Many of the treatments have been published only in small case series or anecdotal reports and do not have well-understood nor proven mechanisms of action. This article presents a comprehensive review of available therapeutic options and long-term management recommendations for the cutaneous porphyrias. © 2013 The International Society of Dermatology.

  5. Unilateral condylar hyperplasia: a treatment strategy.

    PubMed

    Ferreira, Sabrina; da Silva Fabris, André Luis; Ferreira, Gabriel Ramalho; Faverani, Leonardo Perez; Francisconi, Giovanna Barbosa; Souza, Francisley Avila; Garcia, Idelmo Rangel

    2014-05-01

    Condylar hyperplasia (CH) is a pathologic condition that causes overdevelopment of the condylar head and neck as well as the mandible. Slowly progressive unilateral enlargement of the head and the neck of the condyle causes crossbite malocclusion, facial asymmetry, and shifting of the midpoint of the chin to the unaffected side. The etiology and the pathogenesis of CH remain uncertain. The diagnosis is made by clinical and radiologic examinations and bone scintigraph. A difference in uptake of 10% or more between condyles is regarded as indicative of CH, and the affected condyles had a relative uptake of 55% or more. When the diagnosis of active CH is established, the treatment consists of removal of the growth center by a partial condylectomy. The authors present the case of a 46-year-old male patient with right active type II CH or hemimandibular hyperplasia who underwent a high condylectomy.

  6. Treatment strategies for infraoccluded dental implants.

    PubMed

    Zitzmann, Nicola U; Arnold, Dario; Ball, Judith; Brusco, Daniel; Triaca, Albino; Verna, Carlalberta

    2015-03-01

    Single-tooth implants in the maxillary anterior region have the highest risk of esthetic complications from infrapositioning due to continuing maxillary growth and the eruption of adjacent teeth. Although the placement of anterior single-tooth implants should normally be postponed, particularly girls and young women with a hyperdivergent growth pattern, if an infraposition of an implant is present, then thorough examination and strategic planning are required. According to the severity, the strategic treatment options are as follows: simple retention; adjustment or replacement of the implant restoration, possibly including adjacent teeth; surgical implant repositioning by segmental osteotomy combined with osseodistraction; or submergence or removal of the implant. With the patient presented, an interdisciplinary approach that combined orthodontic alignment, surgical segmental osteotomy, distraction osteogenesis, and restorative features offered the opportunity to realign the adjacent teeth into the arch and to harmonize the gingival contour by means of continuous soft tissue enlargement and adaptation.

  7. Epigenomics in hematopoietic transplantation: novel treatment strategies.

    PubMed

    Engel, Nicole; Rank, Andreas

    2011-10-01

    Allogeneic hematopoietic stem cell transplantation is a high risk but curative treatment option for leukemia, myelodysplasia and other hematological malignancies. After high dose radio- or chemo-therapy, recipient's hematopoiesis is replaced by a new immunosystem and residual malignant cells are eliminated by the graft-versus-leukemia reaction. The benefit of this immunological effect is limited by the most frequent complication of hematopoietic stem cell transplantation: graft-versus-host disease. In addition to their well-known anti-tumor activity, epigenetic drugs mediate immunotolerance without reducing alloreactivity or even enhance graft-versus-leukemia effect without inducing graft-versus-host disease by regulating cytokine release, increasing the circulating number of regulatory T cells and interacting with natural killer cells. We focus on the use of epigenetic drugs in the allogeneic transplantation setting in relation to their anti-tumor and immunomodulatory potential.

  8. Endovascular Treatment Strategies in Aortoiliac Occlusion

    SciTech Connect

    Ozkan, Ugur Oguzkurt, Levent Tercan, Fahri Gumus, Burcak

    2009-05-15

    The aim of this study was to report our experience in endovascular treatment of total aortoiliac occlusion. Five patients who underwent endovascular recanalization procedures including manual aspiration thrombectomy, balloon angioplasty, and stent placement for total aortoiliac occlusion in a 4-year period were reviewed retrospectively. The mean age of patients was 51 years (range, 43 to 58 years). All patients had abdominal aorta and bilateral common iliac artery occlusion with or without external iliac artery occlusion. All patients either had a contraindication to surgery or refused it. Initial technical success was obtained in four of five (80%) patients. Endovascular techniques were successful in four patients who had good distal runoff and short-segment aortoiliac occlusion, but failed in a patient who had the worst distal runoff and long-segment aortoiliac occlusion. We observed two major complications, one of which was bilateral rupture of the common iliac arteries treated with covered stent placement. Another patient had extension of intra-aortic thrombus into the iliac stent after primary stenting. This was successfully treated with manual aspiration thrombectomy. Aortic and iliac stents remained patent during the follow-up period (median, 18 months; range, 3 to 26 months) in four patients. Primary patency rates at 6, 12, and 24 months were all 80%. In conclusion, endovascular treatment can be an alternative for aortoiliac occlusion in selected patients. Short- to midterm follow-up so far is satisfactory. Removal of intra-aortic thrombus with manual aspiration thrombectomy before balloon angioplasty and/or stenting is possible and a good alternative to thrombolysis.

  9. Present and New Treatment Strategies in the Management of Glaucoma

    PubMed Central

    Kolko, M.

    2015-01-01

    Glaucoma is a neurodegenerative disease characterized by retinal ganglion cell (RGC) death and axonal loss. It remains a major cause of blindness worldwide. All current modalities of treatment are focused on lowering intraocular pressure (IOP), and it is evident that increased IOP is an important risk factor for progression of the disease. However, it is clear that a significant number of glaucoma patients show disease progression despite of pressure lowering treatments. Much attention has been given to the development of neuroprotective treatment strategies, but the identification of such has been hampered by lack of understanding of the etiology of glaucoma. Hence, in spite of many attempts no neuroprotective drug has yet been clinically approved. Even though neuroprotection is without doubt an important treatment strategy, many glaucoma subjects are diagnosed after substantial loss of RGCs. In this matter, recent approaches aim to rescue RGCs and regenerate axons in order to restore visual function in glaucoma. The present review seeks to provide an overview of the present and new treatment strategies in the management of glaucoma. The treatment strategies are divided into current available glaucoma medications, new pressure lowering targets, prospective neuroprotective interventions, and finally possible neuroregenrative strategies. PMID:26069521

  10. [The future of treatment for chondral and osteochondral lesions].

    PubMed

    Cirpar, Meriç; Korkusuz, Feza

    2007-01-01

    The population of patients with symptomatic focal or generalized cartilage lesions is growing due to prolongation of life expectancy and to increasing frequency of sports injuries. Cartilage tissue lesions which were defined as untreatable in the past have now become treatable thanks to advances in basic scientific research. With the development of technologies regarding biomaterial, cell and local regulators, and with the introduction of new surgical techniques, it is estimated that, in the near future, clinical applications of cartilage tissue engineering will also receive particular attention in our country. Currently, all alternatives used in the treatment of cartilage lesions have merits and demerits, including arthroscopic debridement and lavage, mesenchymal stem cell stimulation, osteochondral replacement techniques, and autologous chondrocyte transplantation. Preliminary results of experimental cartilage tissue engineering are encouraging for the replacement of disrupted tissue with that having mechanical properties of hyaline cartilage. Clinical applications of cartilage tissue engineering include bioabsorbable scaffolds as extracellular collagen, hyaluronic acid matrices, and genetically engineered bioactive materials.

  11. The future of pharmacogenetics in the treatment of heart failure.

    PubMed

    Anwar, Mohamed Subhan; Iskandar, Muhammad Zaid; Parry, Helen M; Doney, Alex S; Palmer, Colin N; Lang, Chim C

    2015-11-01

    Heart failure is a common disease with high levels of morbidity and mortality. Current treatment comprises β-blockers, ACE inhibitors, aldosterone antagonists and diuretics. Variation in clinical response seen in patients begs the question of whether there is a pharmacogenetic component yet to be identified. To date, the genes most studied involve the β-1, β-2, α-2 adrenergic receptors and the renin-angiotensin-aldosterone pathway, mainly focusing on SNPs. However results have been inconsistent. Genome-wide association studies and next-generation sequencing are seen as alternative approaches to discovering genetic variations influencing drug response. Hopefully future research will lay the foundations for genotype-led drug management in these patients with the ultimate aim of improving their clinical outcome.

  12. Social anxiety disorder: designing a pharmacologic treatment strategy.

    PubMed

    Pollack, M H

    1999-01-01

    Growing appreciation of the prevalence of and morbid sequelae associated with social anxiety disorder has focused increasing interest on the development of effective treatment strategies. A number of pharmacologic interventions, including the monoamine oxidase inhibitors, reversible inhibitors of monoamine oxidase A, beta-blockers, benzodiazepines, and selective serotonin reuptake inhibitors, have demonstrated efficacy for the treatment of social anxiety disorder. The choice of initial treatment depends on a variety of factors including comorbidity, prior treatment history, patient preference, and adverse effect profile. This article will examine the effectiveness of various pharmacologic agents for the treatment of social anxiety disorder, discuss considerations for long-term management, and review strategies for optimizing treatment in patients who are partially responsive or unresponsive to initial therapy.

  13. Molecular mechanisms of depression: perspectives on new treatment strategies.

    PubMed

    Lang, Undine E; Borgwardt, Stefan

    2013-01-01

    observed by ketamine, which acts via the glutamatergic system. Hence, GABA, AMPA, EAAT, NMDA- and metabotropic glutamate receptors (mGluR1 to mGluR8) have gained interest in depression recently. Alternative, causative or also easy available treatment strategies beyond serotonin and noradrenaline reuptake inhibition might be a major topic of future psychiatric care. In this review, an attempt is made to overview concepts of the disease and search for perspectives on antidepressant treatment strategies beyond approved medications.

  14. Delayed onset muscle soreness : treatment strategies and performance factors.

    PubMed

    Cheung, Karoline; Hume, Patria; Maxwell, Linda

    2003-01-01

    Delayed onset muscle soreness (DOMS) is a familiar experience for the elite or novice athlete. Symptoms can range from muscle tenderness to severe debilitating pain. The mechanisms, treatment strategies, and impact on athletic performance remain uncertain, despite the high incidence of DOMS. DOMS is most prevalent at the beginning of the sporting season when athletes are returning to training following a period of reduced activity. DOMS is also common when athletes are first introduced to certain types of activities regardless of the time of year. Eccentric activities induce micro-injury at a greater frequency and severity than other types of muscle actions. The intensity and duration of exercise are also important factors in DOMS onset. Up to six hypothesised theories have been proposed for the mechanism of DOMS, namely: lactic acid, muscle spasm, connective tissue damage, muscle damage, inflammation and the enzyme efflux theories. However, an integration of two or more theories is likely to explain muscle soreness. DOMS can affect athletic performance by causing a reduction in joint range of motion, shock attenuation and peak torque. Alterations in muscle sequencing and recruitment patterns may also occur, causing unaccustomed stress to be placed on muscle ligaments and tendons. These compensatory mechanisms may increase the risk of further injury if a premature return to sport is attempted.A number of treatment strategies have been introduced to help alleviate the severity of DOMS and to restore the maximal function of the muscles as rapidly as possible. Nonsteroidal anti-inflammatory drugs have demonstrated dosage-dependent effects that may also be influenced by the time of administration. Similarly, massage has shown varying results that may be attributed to the time of massage application and the type of massage technique used. Cryotherapy, stretching, homeopathy, ultrasound and electrical current modalities have demonstrated no effect on the alleviation of

  15. 17 CFR 30.7 - Treatment of foreign futures or foreign options secured amount.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... FUTURES TRADING COMMISSION FOREIGN FUTURES AND FOREIGN OPTIONS TRANSACTIONS § 30.7 Treatment of foreign futures or foreign options secured amount. (a) Except as provided in this section, a futures commission... options customers denominated as the foreign futures or foreign options secured amount. Such...

  16. Effects of four treatment strategies for temporomandibular joint closed lock

    PubMed Central

    Schiffman, E. L.; Velly, A. M.; Look, J. O.; Hodges, J. S.; Swift, J. Q.; Decker, K. L.; Anderson, Q. N.; Templeton, R. B.; Lenton, P. A.; Kang, W.; Fricton, J. R.

    2013-01-01

    A previous randomized controlled trial (RCT) by Schiffman et al. (2007)15 compared four treatments strategies for temporomandibular joint (TMJ) disc displacement without reduction with limited mouth opening (closed lock). In this parallel group RCT, 106 patients with magnetic resonance imaging (MRI)-confirmed TMJ closed lock were randomized between medical management, non-surgical rehabilitation, arthroscopic surgery, and arthroplasty. Surgical groups also received rehabilitation post-surgically. The current paper reassesses the effectiveness of these four treatment strategies using outcome measures recommended by the International Association of Oral and Maxillofacial Surgeons (IAOMS). Clinical assessments at baseline and at follow-up (3, 6, 12, 18, 24, and 60 months) included intensity and frequency of TMJ pain, mandibular range of motion, TMJ sounds, and impairment of chewing. TMJ MRIs were performed at baseline and 24 months, and TMJ tomograms at baseline, 24 and 60 months. Most IAOMS recommended outcome measures improved significantly over time (P ≤ 0.0003). There was no difference between treatment strategies relative to any treatment outcome at any follow-up (P ≥ 0.16). Patient self-assessment of treatment success correlated with their ability to eat, with pain-free opening ≥35 mm, and with reduced pain intensity. Given no difference between treatment strategies, non-surgical treatment should be employed for TMJ closed lock before considering surgery. PMID:24042068

  17. [Individualized treatment strategies for Clostridium difficile infections].

    PubMed

    Solbach, P; Dersch, P; Bachmann, O

    2017-07-01

    Upon hospitalization, up to 15.5% of patients are already colonized with a toxigenic Clostridium difficile strain (TCD). The rate of asymptomatic colonization is 0-3% in healthy adults and up to 20-40% in hospitalized patients. The incidence and mortality of C. difficile infection (CDI) has significantly increased during recent years. Mortality lies between 3 and 14%. CDI is generally caused by intestinal dysbiosis, which can be triggered by various factors, including antibiotics or immune suppressants. If CDI occurs, ongoing antibiotic therapy should be discontinued. The choice of treatment is guided by the clinical situation: Mild courses of CDI should be treated with metronidazole. Oral vancomycin is suitable as a first-line therapy of mild CDI occurring during pregnancy and lactation, as well as in cases of intolerance or allergy to metronidazole. Severe courses should be treated with vancomycin. Recurrence should be treated with vancomycin or fidaxomicin. Multiple recurrences should be treated with vancomycin or fidaxomicin; if necessary, a vancomycin taper regimen may also be used. An alternative is fecal microbiota transplant (FMT), with healing rates of more than 80%. Bezlotoxumab is the first available monoclonal antibody which neutralizes the C. difficile toxin B, and in combination with an antibiotic significantly reduces the rate of a new C. difficile infection compared to placebo. A better definition of clinical and microbiota-associated risk factors and the ongoing implementation of molecular diagnostics are likely to lead to optimized identification of patients at risk, and an increasing individualization of prophylactic and therapeutic approaches.

  18. Diagnostic and treatment strategies in mucopolysaccharidosis VI

    PubMed Central

    Vairo, Filippo; Federhen, Andressa; Baldo, Guilherme; Riegel, Mariluce; Burin, Maira; Leistner-Segal, Sandra; Giugliani, Roberto

    2015-01-01

    Mucopolysaccharidosis VI (MPS VI) is a very rare autosomal recessive disorder caused by mutations in the ARSB gene, which lead to deficient activity of the lysosomal enzyme ASB. This enzyme is important for the breakdown of the glycosaminoglycans (GAGs) dermatan sulfate and chondroitin sulfate, which accumulate in body tissues and organs of MPS VI patients. The storage of GAGs (especially dermatan sulfate) causes bone dysplasia, joint restriction, organomegaly, heart disease, and corneal clouding, among several other problems, and reduced life span. Despite the fact that most cases are severe, there is a spectrum of severity and some cases are so attenuated that diagnosis is made late in life. Although the analysis of urinary GAGs and/or the measurement of enzyme activity in dried blood spots are useful screening methods, the diagnosis is based in the demonstration of the enzyme deficiency in leucocytes or fibroblasts, and/or in the identification of pathogenic mutations in the ARSB gene. Specific treatment with enzyme replacement has been available since 2005. It is safe and effective, bringing measurable benefits and increased survival to patients. As several evidences indicate that early initiation of therapy may lead to a better outcome, newborn screening is being considered for this condition, and it is already in place in selected areas where the incidence of MPS VI is increased. However, as enzyme replacement therapy is not curative, associated therapies should be considered, and research on innovative therapies continues. The management of affected patients by a multidisciplinary team with experience in MPS diseases is highly recommended. PMID:26586959

  19. Current and Future Treatment Approaches in Transthyretin Familial Amyloid Polyneuropathy.

    PubMed

    Kerschen, Philippe; Planté-Bordeneuve, Violaine

    2016-12-01

    Treatment of transthyretin familial amyloid polyneuropathy (TTR FAP) must be tailored to disease stage. Patients with early stage disease (i.e., without major impairment in walking ability), especially younger patients, should be referred as soon as possible for liver transplantation (LT) in the absence of major comorbid conditions. LT remains the most effective treatment option to date and should be offered to these patients as early as possible. Bridging therapy with an oral TTR stabilizer (tafamidis or diflunisal, according to local access to these treatments) should be started as soon as the diagnosis of TTR FAP is established. Early stage patients who do not wish to or have contraindications to LT should be treated with an oral TTR stabilizer or get access to the newly developed therapeutic options (IONIS TTR-Rx, patisiran, doxycycline/TUDCA). Late stage patients (presenting with significant walking impairment) are usually older and notoriously difficult to treat. They should be offered an oral TTR stabilizer but are not candidates for LT due to a significant rate of perioperative complications and increased risk of progressive neurological and especially cardiac disease despite LT. Access to the different therapies in development should also be considered depending on respective inclusion and exclusion criteria. The abovementioned treatment options were mostly validated in Val30Met mutation patients, but should also be offered to non-Val30Met patients, although mortality rates after LT are higher in these patients. Treatment decisions should be made on an individual basis. Screening for heart, eye, and renal involvement is mandatory for every patient at disease diagnosis and regularly thereafter, even in transplanted patients. Symptomatic treatment should be offered as needed, as well as genetic counseling to at-risk family members. Asymptomatic mutation carriers should benefit from regular screening for early symptoms of disease. Current therapeutic

  20. Transportation Energy Futures: Combining Strategies for Deep Reductions in Energy Consumption and GHG Emissions (Brochure)

    SciTech Connect

    Not Available

    2013-03-01

    This fact sheet summarizes actions in the areas of light-duty vehicle, non-light-duty vehicle, fuel, and transportation demand that show promise for deep reductions in energy use. Energy efficient transportation strategies have the potential to simultaneously reduce oil consumption and greenhouse gas (GHG) emissions. The Transportation Energy Futures (TEF) project examined how the combination of multiple strategies could achieve deep reductions in GHG emissions and petroleum use on the order of 80%. Led by NREL, in collaboration with Argonne National Laboratory, the project's primary goal was to help inform domestic decisions about transportation energy strategies, priorities, and investments, with an emphasis on underexplored opportunities. TEF findings reveal three strategies with the potential to displace most transportation-related petroleum use and GHG emissions: 1) Stabilizing energy use in the transportation sector through efficiency and demand-side approaches. 2) Using additional advanced biofuels. 3) Expanding electric drivetrain technologies.

  1. Neurogenic ejaculatory disorders: focus on current and future treatments.

    PubMed

    Calabrò, Rocco S; Polimeni, Giovanni; Ciurleo, Rosella; Casella, Carmela; Bramanti, Placido

    2011-09-01

    Ejaculation is a complex and still poorly understood neurological mechanism, at both spinal and cerebral levels as it is closely associated with orgasm. Physiologically, ejaculation is defined as the expulsion of seminal fluid from the urethral meatus and consists of two phases, namely emission and expulsion. Ejaculation is mediated by a spinal control center, referred to as a spinal pattern generator that coordinates sympathetic, parasympathetic and motor (somatic) outflows, integrating the latter with the inputs from the supraspinal sites in brainstem, hypothalamus and preoptic area. Premature ejaculation (PE) is the most common sexual dysfunction among young men, and it has been considered mostly psychogenic in origin, although it can be associated to diverse urological and neurological diseases. On the contrary, retrograde ejaculation and anejaculation are predominantly related to organic causes, particularly to neurogenic ones. Since ejaculation is mostly a spinal reflex, it is comprehensible that ejaculatory disorders are more frequent in spinal cord injury than in other neurological disorders. Over the past decades, research has focused on PE, and evidence from clinical studies showed a beneficial effect of antidepressants for the treatment of men with PE. Other ejaculatory disorders, especially painful ejaculation, have been less investigated and the proper therapy is still controversial. Aim of this review is to provide a comprehensive description of both currently available treatments and most promising future therapies, including assigned patents, for the neurogenic ejaculatory disorders.

  2. Metastatic disease from uveal melanoma: treatment options and future prospects.

    PubMed

    Carvajal, Richard D; Schwartz, Gary K; Tezel, Tongalp; Marr, Brian; Francis, Jasmine H; Nathan, Paul D

    2017-01-01

    Uveal melanoma represents ∼85% of all ocular melanomas and up to 50% of patients develop metastatic disease. Metastases are most frequently localised to the liver and, as few patients are candidates for potentially curative surgery, this is associated with a poor prognosis. There is currently little published evidence for the optimal management and treatment of metastatic uveal melanoma and the lack of effective therapies in this setting has led to the widespread use of systemic treatments for patients with cutaneous melanoma. Uveal and cutaneous melanomas are intrinsically different diseases and so dedicated management strategies and therapies for uveal melanoma are much needed. This review explores the biology of uveal melanoma and how this relates to ongoing trials of targeted therapies in the metastatic disease setting. In addition, we consider the options to optimise patient management and care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  3. Treatment of preeclampsia: current approach and future perspectives.

    PubMed

    Berzan, Ecaterina; Doyle, Ross; Brown, Catherine M

    2014-09-01

    Hypertension is the most common medical disorder encountered during pregnancy, occurring in about 6-8 % of pregnancies. Preeclampsia is a pregnancy-specific disorder that occurs after 20 weeks' gestation, characterized by hypertension and proteinuria. Preeclampsia can also occur superimposed upon chronic hypertension. Eclampsia is the convulsive form of preeclampsia, and affects 0.1 % of all pregnancies. In low-income and middle-income countries, preeclampsia and eclampsia are associated with 10-15 % of direct maternal deaths. Women who develop preeclampsia in pregnancy are at greater risk of cardiovascular and cerebrovascular events even years after their pregnancies. There is significant progress in the elucidation of the underlying mechanisms and pathophysiology of preeclampsia, although its therapeutics remains challenging; delivery of the fetus is still the definitive treatment. Different international societies have produced recommendations and guidelines for clinicians treating preeclampsia, with an overall goal of improving maternal and fetal outcomes. In this review, we focus on the level of blood pressure at which to commence treatment and the current clinical management strategies available to treat and possibly prevent preeclampsia. We also briefly outline some newer perspectives on management of the disorder.

  4. Treatment trials in ankylosing spondylitis: current and future considerations

    PubMed Central

    van der Heijde, D; Braun, J; McGonagle, D; Siegel, J

    2002-01-01

    Emerging treatment options in ankylosing spondylitis (AS) are giving new hope to patients with this chronic and potentially disabling disease. Clinical development of new treatments requires that rigorous and well controlled trials be conducted to demonstrate safety and efficacy. A number of classification systems have been developed in recent years as a result of enhanced understanding of the pathogenesis of AS. Although new outcome measures have been developed and a consensus has been reached on the use of assessment instruments in clinical trials, there is still need for improvement and implementation. The ASsessments in Ankylosing Spondylitis (ASAS) Working Group has addressed some of these dilemmas by establishing a core set of domains for the evaluation of AS and by selecting specific assessment methods for each domain. They have also published improvement criteria for assessing short term improvement with symptom modifying antirheumatic drugs and are presently in the process of developing response criteria for disease controlling antirheumatic treatment. Various experts are also currently examining discrepancies and inadequacies of classification systems for AS. Imaging studies, magnetic resonance imaging, in particular, may provide better classification criteria in the near future. In addition to consensus on outcome assessment and classification of AS, lessons learnt from clinical trials in rheumatoid arthritis (RA) may serve as a template for AS. Guidance provided by the United States Food and Drug Administration (FDA) for clinical trials in RA may be of particular use. The FDA has defined the claims that sponsors can receive for RA products and the clinical trial data that would be expected to be submitted to support such claims. PMID:12381508

  5. [Understanding and treatment strategy for disc displacement of temporomandibular disorders].

    PubMed

    Ma, X C

    2017-03-09

    Understanding and treatment strategy for disc displacement of temporomandibular disorders (TMD) were discussed in the present review. It has been strongly recommended by the author that the treatment strategy for disc displacement, one subtype of TMD, should be mainly the reversible conservative treatment methods. The most important goal of treatment for disc displacement is to recover the mobility and function of the joint in order to improve the quality of the patient's life. Comprehensive assessments both from somatic and psychological aspects for each TMD patient are necessary, especially for the patients with chronic pain. Although the role of surgical operative treatments is very limited in the general treatment strategy for TMD, it is still important for a few patients who had definite diagnosis of intra-articular disorders, severe symptoms affecting the quality of patient's life and failed to response to the correct conservative treatments. It should be very careful to treat the TMD patients by surgical operation or irreversible occlusion treatments changing the natural denture of the patient, such as full mouth occlusional reconstruction and extensive adjustment of occlusion.

  6. Cell-penetrating peptides: strategies for anticancer treatment.

    PubMed

    Raucher, Drazen; Ryu, Jung Su

    2015-09-01

    Cell-penetrating peptides (CPP) provide an efficient strategy for the intracellular delivery of bioactive molecules in various biomedical applications. This review focuses on recent advances in the use of CPPs to deliver anticancer therapeutics and imaging reagents to cancer cells, along with CPP contributions to novel tumor-targeting techniques. CPPs are now used extensively to deliver a variety of therapeutics, despite lacking cell specificity and having a short duration of action. Resolution of these shortcomings to enable increased cancer cell and/or tumor specificity could improve CPP-based drug delivery strategies, expand combined drug delivery possibilities, and strengthen future clinical applications of these peptides.

  7. Gasoline direct injection: Actual trends and future strategies for injection and combustion systems

    SciTech Connect

    Fraidl, G.K.; Piock, W.F.; Wirth, M.

    1996-09-01

    Recent developments have raised increased interest on the concept of gasoline direct injection as the most promising future strategy for fuel economy improvement of SI engines. The general requirements for mixture preparation and combustion systems in a GDI engine are presented in view of known and actual systems regarding fuel economy and emission potential. The characteristics of the actually favored injection systems are discussed and guidelines for the development of appropriate combustion systems are derived. The differences between such mixture preparation strategies as air distributed fuel and fuel wall impingement are discussed, leading to the alternative approach to the problem of mixture preparation with the fully air distributing concept of direct mixture injection.

  8. An update on treatment and prevention strategies for Alzheimer's disease.

    PubMed

    Neugroschl, Judith; Sano, Mary

    2009-09-01

    With the aging of the population, the incidence and prevalence of Alzheimer's disease will grow, increasing the burden on individuals and society. While ameliorating symptoms, the currently available treatments approved by the US Food and Drug Administration do not halt progression or cure the illness. This article discusses recent data on treatment strategies targeting amyloid and tau pathology. Novel therapeutic strategies such as inhibitors of receptors for advanced glycation end products (RAGE), potential mitochondrial modification with Dimebon, anti-inflammatory approaches, and cholesterol-lowering agents are also reviewed. An update on results from pharmacologic and nonpharmacologic prevention trials is provided.

  9. Ethical Concerns Related to Developing Pharmacogenomic Treatment Strategies for Addiction

    PubMed Central

    Shields, Alexandra E.

    2011-01-01

    Pharmacogenomics (PGx) research is poised to enable physicians to identify optimally effective treatments for individual substance abusers based on their genetic profiles. This paper addresses ethical issues related to PGx treatment strategies for addiction, focusing especially on the use of race variables in genomics research and ensuring equitable access to novel PGx treatments. Unless the field addresses the ethical challenges posed by these issues, PGx treatment innovations for addiction threaten to exacerbate already dramatic disparities in the burden of drug dependence for minority and other underserved populations. PMID:22003420

  10. Cross-Cultural Competency in the General Purpose Force: Training Strategies and Implications for Future Operations

    DTIC Science & Technology

    2013-04-09

    SUBTITLE Cross-Cultural Competency in the General Purpose Force: Training Strategies and Implications for Future Operations 5a. CONTRACT NUMBER N/A...NOTES N/A 14. ABSTRACT An abundance of research in Cross-Cultural Competency (C3) is conclusive in recognizing the value it has for General Purpose...might currently be in jeopardy. 15. SUBJECT TERMS Culture, Cross Cultural Competency , Cultural Agility, General Purpose Forces, Marine Corps Center

  11. Is one technology best? Control strategies to meet current and future regulations

    SciTech Connect

    Altin, C.A.; Bustard, C.J.; Gelfand, P.; Sloat, D.G.; Belba, V.H.

    1994-12-31

    A slide presentation is given that discusses control strategies to meet current and future regulations. Most new regulations will require incremental reductions in specific emissions creating a market for technologies that can be retrofitted to existing systems. Since most metals are associated with particulate matter, improving particle collection will lead to reduced metal emissions and the disposal of sorbents used for capturing vapor phase pollutants, e.g., SO{sub 2} and Hg, can dominate the economics of the process.

  12. Benign Paroxysmal Positional Vertigo (BPPV): History, Pathophysiology, Office Treatment and Future Directions.

    PubMed

    Hornibrook, Jeremy

    2011-01-01

    BPPV is the most common cause of vertigo. It most often occurs spontaneously in the 50 to 70 year age group. In younger individuals it is the commonest cause of vertigo following head injury. There is a wide spectrum of severity from inconsistent positional vertigo to continuous vertigo provoked by any head movement. It is likely to be a cause of falls and other morbidity in the elderly. Misdiagnosis can result in unnecessary tests. The cardinal features and a diagnostic test were clarified in 1952 by Dix and Hallpike. Subsequently, it has been established that the symptoms are attributable to detached otoconia in any of the semicircular canals. BPPV symptoms can resolve spontaneously but can last for days, weeks, months, and years. Unusual patterns of nystagmus and nonrepsonse to treatment may suggest central pathology. Diagnostic strategies and the simplest "office" treatment techniques are described. Future directions for research are discussed.

  13. Treatment of epilepsy: existing therapies and future developments.

    PubMed

    Aiken, S P; Brown, W M

    2000-11-01

    Epilepsy is a major public health issue, not least because of the aging population in many developed nations and the known increase in the frequency of epilepsy and seizures in later life. Despite the massive scale of the problem and much research, epilepsy remains poorly understood. Despite more than 20 approved drugs in the developed nations and several non-pharmacological options, up to 30% of patients are still refractory to treatment. Despite over a century of pharmacotherapy and neuroscience research, rational design of anti-epileptic drugs (AEDs) is only now starting to yield results, because of the heterogeneity of the disease and our still limited understanding of it. Discovery and development of AEDs has been especially difficult, because of the regulatory issues of satisfactorily proving safety and efficacy, ethical constraints on placebo-controlled trial designs, the fact that seizures are typically widely spaced in time, and the fact that the person undergoing the seizure is typically in no state to remember, let alone assess, what happened. Several non-pharmacological therapies have been developed: brain surgery was first used more than a century ago; the ketogenic diet was first developed 80 years ago; and the vagus nerve stimulator was introduced recently. Pharmacotherapy remains the mainstay of treatment and is effective in most patients. AEDs can be roughly divided according to their time on the market. The first generation extends from the bromides and the barbiturates (the first of which was phenobarbital), to sodium valproate and carbamazepine. The second generation begins with felbamate and includes drugs approved from 1993 to 2000. "Next generation" drugs are still in clinical development and may reach the marketplace in the near future. Intensive research is being conducted both by pharmaceutical and biotech companies and by academic scientists and clinicians; our understanding of the condition is advancing rapidly but many challenges remain

  14. Current, new and future treatments in dyslipidaemia and atherosclerosis.

    PubMed

    Chong, P H; Bachenheimer, B S

    2000-07-01

    investigational agents are inhibitors of squalene synthetase, acylCoA: cholesterol acyltransferase, cholesteryl ester transfer protein, monocyte-macrophages and LDL cholesterol oxidation. Future applications may include thyromimetic therapy, cholesterol vaccination, somatic gene therapy, and recombinant proteins, in particular, apolipoproteins A-I and E. Non-LDL-related targets such as peroxisome proliferator-activating receptors, matrix metalloproteinases and scavenger receptor class B type I may also have clinical significance in the treatment of atherosclerosis in the near future. Before lipid-lowering therapy, dietary and lifestyle modification is and should be the first therapeutic intervention in the management of dyslipidaemia. Although current recommendations from the US and Europe are slightly different, adherence to these recommendations is essential to lower the risk of atherosclerotic vascular disease, more specifically CHD. New guidelines that are expected in the near future will encompass global opinions from the expert scientific community addressing the issue of target LDL goal (aggressive versus moderate lowering) and the application of therapy for newer emerging CHD risk factors.

  15. Traumatic brain injury: future assessment tools and treatment prospects

    PubMed Central

    Flanagan, Steven R; Cantor, Joshua B; Ashman, Teresa A

    2008-01-01

    Traumatic brain injury (TBI) is widespread and leads to death and disability in millions of individuals around the world each year. Overall incidence and prevalence of TBI are likely to increase in absolute terms in the future. Tackling the problem of treating TBI successfully will require improvements in the understanding of normal cerebral anatomy, physiology, and function throughout the lifespan, as well as the pathological and recuperative responses that result from trauma. New treatment approaches and combinations will need to be targeted to the heterogeneous needs of TBI populations. This article explores and evaluates the research evidence in areas that will likely lead to a reduction in TBI-related morbidity and improved outcomes. These include emerging assessment instruments and techniques in areas of structural/chemical and functional neuroimaging and neuropsychology, advances in the realms of cell-based therapies and genetics, promising cognitive rehabilitation techniques including cognitive remediation and the use of electronic technologies including assistive devices and virtual reality, and the emerging field of complementary and alternative medicine. PMID:19183780

  16. Discovery of new molecules for future treatment of infertility.

    PubMed

    Palmer, Stephen S; McKenna, Sean; Arkinstall, Steve

    2005-06-01

    The introduction of recombinant gonadotrophins for the treatment of infertility has been an important advance in improving the quality and consistency of therapeutics offered to patients seeking care from fertility specialists. Over the past decade, a number of investigators have discovered small molecules that mimic the effects of FSH and LH. Despite extensive medicinal chemistry efforts from many institutes, including Serono Research Institute, and reasonable in-vitro activity, receptor-targeted agonists have not yet been successfully developed for clinical use, based upon results generated in animal models of follicular stimulation (FSH-like) or ovulation induction [human chorionic gonadotrophin (HCG)-like]. A different approach to gonadotrophin mimicry was identified that modifies intracellular signalling pathways common to gonadotrophins. Phosphodiesterase type 4 enzyme inhibitors and selective prostaglandin E receptor (EP2/EP4) agonists have been demonstrated to mimic the effects of HCG to induce ovulation following oral administration. Multiple approaches with small molecules have been attempted to activate the FSH receptor and initiate cAMP-dependent mechanisms. Pharmacodynamic effects of FSH on follicular growth were demonstrated by inhibiting a different enzyme pathway with a small molecule, albeit in the presence of very low concentrations of circulating FSH. These results raise the possibility that in the future orally active agents can be used in combination with injectable gonadotrophins or perhaps independent of gonadotrophins for first-line interventions for infertility.

  17. High Priority Future Research Needs for Obstructive Sleep Apnea Diagnosis and Treatment

    PubMed Central

    Patel, Kamal; Moorthy, Denish; Chan, Jeffrey A.; Concannon, Thomas W.; Ratichek, Sara J.; Chung, Mei; Balk, Ethan M.

    2013-01-01

    Study Objectives: To identify and prioritize future research needs (FRN) topics for diagnosis and treatment of obstructive sleep apnea (OSA). Methods: Twenty-one panel members represented six stake-holder categories: patients and the public, providers; purchasers of health care, payers, policymakers, and principal investigators. Building on a recently completed comparative effectiveness review, stakeholders nominated and discussed potential FRN topics. Stakeholders then nominated their top priority FRN topics based on the Agency for Healthcare Research and Quality Effective Health Care Program Selection Criteria. From these nominations, the highest priority FRN topics were determined and were elaborated upon to include possible study designs to address the topics. Results: Thirty-seven topics were discussed and prioritized. The nine highest priority FRN topics included: cost-effectiveness of management strategies, defining age- and sex-specific criteria for OSA, evaluating routine preoperative screening for OSA, evaluating involvement of a sleep medicine specialist in diagnosis of OSA, evaluating clinical prediction rules, assessing the effect of treating sleep disordered breathing and long-term clinical outcomes, comparing treatments for patients who do not tolerate positive airway pressure, evaluating strategies to improve treatment compliance, and evaluating the association between sleep apnea severity and long-term clinical outcomes. Conclusions: While there are numerous specific research questions with low or insufficient strength of evidence for OSA management, OSA patients, their healthcare providers, and society at large would benefit from refocusing research efforts into the prioritized research questions and away from simple comparisons of short-term outcomes between specific interventions. Citation: Patel K; Moorthy D; Chan JA; Concannon TW. High priority future research needs for obstructive sleep apnea diagnosis and treatment. J Clin Sleep Med 2013

  18. Creating the laboratory`s future; A strategy for Lawrence Livermore National Laboratory

    SciTech Connect

    1997-09-01

    ``Creating The Laboratory`s Future`` describes Livermore`s roles and responsibilities as a Department of Energy (DOE) national laboratory and sets the foundation for decisions about the Laboratory`s programs and operations. It summarizes Livermore`s near-term strategy, which builds on recent Lab achievements and world events affecting their future. It also discusses their programmatic and operational emphases and highlights program areas that the authors believe can grow through application of Lab science and technology. Creating the Laboratory`s Future reflects their very strong focus on national security, important changes in the character of their national security work, major efforts are under way to overhaul their administrative and operational systems, and the continuing challenge of achieving national consensus on the role of the government in energy, environment, and the biosciences.

  19. Understanding latent tuberculosis: the key to improved diagnostic and novel treatment strategies

    PubMed Central

    Esmail, Hanif; Barry, Clifton E; Wilkinson, Robert J

    2012-01-01

    Treatment of latent tuberculosis (LTBI) is a vital component of tuberculosis elimination but is not efficiently implemented with available diagnostics and therapeutics. The tuberculin skin test and interferon gamma release assays can inform that infection has occurred but do not prove that it persists. Treatment of LTBI with isoniazid targets actively replicating bacilli but not non-replicating populations, prolonging treatment duration. Developing more predictive diagnostic tests and treatments of shorter duration requires a greater understanding of the biology of latent tuberculosis, from both host and bacillary perspectives. In this article we discuss the basis of current diagnosis and treatment of LTBI and review recent developments in understanding the biology of latency that may enable future improved diagnostic and treatment strategies. PMID:22198298

  20. Changes in pain-related coping strategies and their importance for treatment outcome following multimodal inpatient treatment: does sex matter?

    PubMed

    Hechler, Tanja; Kosfelder, Joachim; Vocks, Silja; Mönninger, Theresa; Blankenburg, Markus; Dobe, Michael; Gerlach, Alexander L; Denecke, Heide; Zernikow, Boris

    2010-05-01

    While sex differences in pain-related coping have been widely reported, little is known on sex differences in changes in coping following multimodal pain treatment and how these changes relate to treatment outcome. The present prospective study therefore aimed to investigate sex differences in coping strategies between boys and girls with chronic pain prior to multimodal inpatient treatment and at 3-month follow-up. Sixty-four boys and 103 girls with various pain disorders were evaluated. Core outcomes (pain intensity and pain-related disability) and coping were assessed via validated questionnaires. At admission, boys and girls used similar coping strategies. Three months following treatment, boys and girls decreased passive pain coping and seeking social support while they maintained the degree of positive self-instruction. Girls displayed higher seeking social support than boys and of importance, only for girls, a reduction in seeking social support was related to decreases in pain intensity. In both groups, the changes in coping were related to positive treatment outcome. Results suggest that both groups may benefit from reductions in passive pain coping and seeking social support. The causal quality of this relationship remains to be determined in future studies. Gender-role expectations and family interactions may account for the sex differences demonstrated for seeking social support. Boys and girls with chronic pain show profound similarities in pain-related coping strategies prior and after multimodal pain treatment. The changes in coping are related to positive treatment outcomes. Sex-specific treatment strategies for changing seeking social support may need to be developed and tested for their differential efficacy in boys and girls. Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.

  1. Comparing a stratified treatment strategy with the standard treatment in randomized clinical trials.

    PubMed

    Sun, Hong; Bretz, Frank; Gerke, Oke; Vach, Werner

    2016-12-20

    The increasing emergence of predictive markers for different treatments in the same patient population allows us to define stratified treatment strategies. We consider randomized clinical trials that compare a standard treatment with a new stratified treatment strategy that divides the study population into subgroups receiving different treatments. Because the new strategy may not be beneficial in all subgroups, we consider in this paper an intermediate approach that establishes a treatment effect in a subset of patients built by joining several subgroups. The approach is based on the simple idea of selecting the subset with minimal p-value when testing the subset-specific treatment effects. We present a framework to compare this approach with other approaches to select subsets by introducing three performance measures. The results of a comprehensive simulation study are presented, and the relative merits of the various approaches are discussed. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Functional Mitral Regurgitation: Appraising the Evidence Behind Recommended Treatment Strategies.

    PubMed

    Samad, Zainab; Velazquez, Eric J

    2016-12-01

    Functional mitral regurgitation (MR) is the most common type of MR encountered in clinical practice. Because the disease arises from the ventricular aspect of the mitral valve apparatus, treatment therapies are less defined and outcomes are poor. In this review, the state of evidence for medical and surgical therapy in functional MR is appraised. Future directions for research in this area are also defined.

  3. Novel Interventional Strategies for the Treatment of Atrial Fibrillation

    PubMed Central

    Siontis, Konstantinos C; Oral, Hakan

    2016-01-01

    The landscape of the invasive management of atrial fibrillation, the most common sustained arrhythmia in humans, has changed dramatically in the last decade owing to numerous advances in arrhythmia mapping and ablation technologies. The current review critically appraises novel interventional strategies for the treatment of atrial fibrillation with a focus on clinical effectiveness and safety. PMID:27403294

  4. Treatment strategies for aneurysms associated with moyamoya disease.

    PubMed

    Zhang, Lei; Xu, Kan; Zhang, Yandong; Wang, Xin; Yu, Jinlu

    2015-01-01

    The treatment of aneurysms associated with moyamoya disease (MMD) is difficult for neurosurgeons, and little is known of strategy options. This report constitutes a comprehensive review of the literature. We summarize the known treatments and their clinical outcomes according to the site of the aneurysm: in major arteries, peripheral arteries, moyamoya vessels, meningeal arteries, or at the site of anastomosis. The literature review indicates that the treatment of MMD-associated aneurysms varies according to the site of the aneurysm and its hemodynamic characteristics. In particular, the treatment for basilar tip aneurysms remains challenging, since both endovascular embolization and direct clipping are difficult. The potential risk for ischemia should be considered in selecting endovascular or surgical approaches. Revascularization surgery, which is important for the treatment of MMD, also determines the clinical treatment outcome of aneurysms associated with MMD.

  5. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma: biological insights and early treatment strategies.

    PubMed

    Landgren, Ola

    2013-01-01

    After decades of virtually no progress, multiple myeloma survival has improved significantly in the past 10 years. Indeed, multiple myeloma has perhaps seen more remarkable progress in treatment and patient outcomes than any other cancer during the last decade. Recent data show that multiple myeloma is consistently preceded by a precursor state (monoclonal gammopathy of undetermined significance [MGUS]/smoldering multiple myeloma [SMM]). This observation provides a framework for prospective studies focusing on transformation from precursor disease to multiple myeloma and for the development of treatment strategies targeting "early myeloma." This review discusses current biological insights in MGUS/SMM, provides an update on clinical management, and discusses how the integration of novel biological markers, molecular imaging, and clinical monitoring of MGUS/SMM could facilitate the development of early treatment strategies for high-risk SMM (early myeloma) patients in the future.

  6. Optimal management of familial hypercholesterolemia: treatment and management strategies

    PubMed Central

    Nemati, Mohammad Hassan; Astaneh, Behrooz

    2010-01-01

    Familial hypercholesterolemia is an autosomally dominant disorder caused by various mutations in low-density lipoprotein receptor genes. This will lead to elevated levels of total and low-density lipoprotein cholesterol, which may in turn lead to premature coronary atherosclerosis and cardiac-related death. The symptoms are more severe in the homozygous type of the disease. Different options for the treatment of affected patients are now available. Diet therapy, pharmacologic therapy, lipid apheresis, and liver transplantation are among the various treatments. We clinically review the treatment and management strategies for the disease in order to shed light on the optimal management of familial hypercholesterolemia. PMID:21191428

  7. Evaluating different strategies for estimating treatment effects in observational studies.

    PubMed

    Zagar, Anthony J; Kadziola, Zbigniew; Lipkovich, Ilya; Faries, Douglas E

    2017-01-01

    Since the introduction of the propensity score (PS), methods for estimating treatment effects with observational data have received growing attention in the literature. Recent research has added substantially to the number of available statistical approaches for controlling confounding in such analyses. However, researchers need guidance to decide on the optimal analytic strategy for any given scenario. To address this gap, we conducted simulations evaluating both well-established methods (regression, PS weighting, stratification, and matching) and more recently proposed approaches (tree-based methods, local control, entropy balancing, genetic matching, prognostic scoring). The simulation scenarios included tree-based and smooth regression models as true data-generation mechanisms. We evaluated an extensive number of analysis strategies combining different treatment choices and outcome models. Key findings include 1) the lack of a single best strategy across all potential scenarios; 2) the importance of appropriately addressing interactions in the treatment choice model and/or outcome model; and 3) a tree-structured treatment choice model and a polynomial outcome model with second-order interactions performed well. One limitation to this initial assessment is the lack of heterogeneous simulation scenarios allowing treatment effects to vary by patient.

  8. The Leader of the Future. New Visions, Strategies, and Practices for the Next Era. First Edition. Drucker Foundation Future Series.

    ERIC Educational Resources Information Center

    Hesselbein, Frances, Ed.; And Others

    The 31 papers in this volume address the requirements and qualities of leadership and leaders in the organization of the future. Papers are grouped into the following categories: Leading the Organization of the Future, Future Leaders in Action, Learning to Lead for Tomorrow, and Executives on the Future of Leadership. Some of the papers included…

  9. The Leader of the Future. New Visions, Strategies, and Practices for the Next Era. First Edition. Drucker Foundation Future Series.

    ERIC Educational Resources Information Center

    Hesselbein, Frances, Ed.; And Others

    The 31 papers in this volume address the requirements and qualities of leadership and leaders in the organization of the future. Papers are grouped into the following categories: Leading the Organization of the Future, Future Leaders in Action, Learning to Lead for Tomorrow, and Executives on the Future of Leadership. Some of the papers included…

  10. An Assessment of Thermodynamic Merits for Current and Potential Future Engine Operating Strategies

    SciTech Connect

    Wissink, Martin L; Splitter, Derek A; Dempsey, Adam B; Curran, Scott; Kaul, Brian C; Szybist, James P

    2017-01-01

    The present work compares the fundamental thermodynamic underpinnings (i.e., working fluid properties and heat release profile) of various combustion strategies with engine measurements. The approach employs a model that separately tracks the impacts on efficiency due to differences in rate of heat addition, volume change, mass addition, and molecular weight change for a given combi-nation of working fluid, heat release profile, and engine geometry. Comparative analysis between measured and modelled efficiencies illustrates fundamental sources of efficiency reductions or oppor-tunities inherent to various combustion regimes. Engine operating regimes chosen for analysis include stoichiometric spark-ignited combustion and lean compression-ignited combustion including HCCI, SA-HCCI, RCCI, GCI, and CDC. Within each combustion regime, effects such as engine load, combustion duration, combustion phasing, combustion chamber geometry, fuel properties, and charge dilution are explored. Model findings illustrate that even in the absence of losses such as heat transfer or incom-plete combustion, the maximum possible thermal efficiency inherent to each operating strategy varies to a significant degree. Additionally, the experimentally measured losses are observed to be unique within a given operating strategy. The findings highlight the fact that in order to create a roadmap for future directions in ICE technologies, it is important to not only compare the absolute real-world effi-ciency of a given combustion strategy, but to also examine the measured efficiency in context of what is thermodynamically possible with the working fluid and boundary conditions prescribed by a strategy.

  11. An assessment of thermodynamic merits for current and potential future engine operating strategies

    DOE PAGES

    Wissink, Martin L.; Splitter, Derek A.; Dempsey, Adam B.; ...

    2017-02-01

    The present work compares the fundamental thermodynamic underpinnings (i.e., working fluid properties and heat release profile) of various combustion strategies with engine measurements. The approach employs a model that separately tracks the impacts on efficiency due to differences in rate of heat addition, volume change, mass addition, and molecular weight change for a given combination of working fluid, heat release profile, and engine geometry. Comparative analysis between measured and modeled efficiencies illustrates fundamental sources of efficiency reductions or opportunities inherent to various combustion regimes. Engine operating regimes chosen for analysis include stoichiometric spark-ignited combustion and lean compression-ignited combustion including HCCI,more » SA-HCCI, RCCI, GCI, and CDC. Within each combustion regime, effects such as engine load, combustion duration, combustion phasing, combustion chamber geometry, fuel properties, and charge dilution are explored. Model findings illustrate that even in the absence of losses such as heat transfer or incomplete combustion, the maximum possible thermal efficiency inherent to each operating strategy varies to a significant degree. Additionally, the experimentally measured losses are observed to be unique within a given operating strategy. The findings highlight the fact that in order to create a roadmap for future directions in ICE technologies, it is important to not only compare the absolute real-world efficiency of a given combustion strategy, but to also examine the measured efficiency in context of what is thermodynamically possible with the working fluid and boundary conditions prescribed by a strategy.« less

  12. [Diagnostics and treatment strategies for multiple trauma patients].

    PubMed

    Pfeifer, R; Pape, H-C

    2016-02-01

    Severe trauma is still one of the leading causes of death worldwide. The initial treatment and diagnostics are of immense importance in polytraumatized patients. The initial approach mainly focuses on the advanced trauma life support (ATLS) concept. This includes the identification of life-threatening conditions and application of life-saving interventions. Depending on the physiological condition of the patient, the surgical treatment strategies of early total care (ETC) or damage control orthopedics (DCO) can be chosen. Appropriate surgical management can reduce the incidence of associated delayed systemic complications. This review summarizes the most commonly used definitions of polytrauma (including the Berlin polytrauma definition) and classification systems of severely injured patients. Moreover, the recently introduced treatment strategy of the safe definitive surgery concept for severely injured patients is also discussed in this article.

  13. Cognitive Impairment in Bipolar Disorder: Treatment and Prevention Strategies

    PubMed Central

    Solé, Brisa; Jiménez, Esther; Torrent, Carla; Reinares, Maria; Bonnin, Caterina del Mar; Torres, Imma; Varo, Cristina; Grande, Iria; Valls, Elia; Salagre, Estela; Sanchez-Moreno, Jose; Martinez-Aran, Anabel; Carvalho, André F

    2017-01-01

    Abstract Over the last decade, there has been a growing appreciation of the importance of identifying and treating cognitive impairment associated with bipolar disorder, since it persists in remission periods. Evidence indicates that neurocognitive dysfunction may significantly influence patients’ psychosocial outcomes. An ever-increasing body of research seeks to achieve a better understanding of potential moderators contributing to cognitive impairment in bipolar disorder in order to develop prevention strategies and effective treatments. This review provides an overview of the available data from studies examining treatments for cognitive dysfunction in bipolar disorder as well as potential novel treatments, from both pharmacological and psychological perspectives. All these data encourage the development of further studies to find effective strategies to prevent and treat cognitive impairment associated with bipolar disorder. These efforts may ultimately lead to an improvement of psychosocial functioning in these patients. PMID:28498954

  14. Advanced therapies for the treatment of hemophilia: future perspectives

    PubMed Central

    2012-01-01

    Monogenic diseases are ideal candidates for treatment by the emerging advanced therapies, which are capable of correcting alterations in protein expression that result from genetic mutation. In hemophilia A and B such alterations affect the activity of coagulation factors VIII and IX, respectively, and are responsible for the development of the disease. Advanced therapies may involve the replacement of a deficient gene by a healthy gene so that it generates a certain functional, structural or transport protein (gene therapy); the incorporation of a full array of healthy genes and proteins through perfusion or transplantation of healthy cells (cell therapy); or tissue transplantation and formation of healthy organs (tissue engineering). For their part, induced pluripotent stem cells have recently been shown to also play a significant role in the fields of cell therapy and tissue engineering. Hemophilia is optimally suited for advanced therapies owing to the fact that, as a monogenic condition, it does not require very high expression levels of a coagulation factor to reach moderate disease status. As a result, significant progress has been possible with respect to these kinds of strategies, especially in the fields of gene therapy (by using viral and non-viral vectors) and cell therapy (by means of several types of target cells). Thus, although still considered a rare disorder, hemophilia is now recognized as a condition amenable to gene therapy, which can be administered in the form of lentiviral and adeno-associated vectors applied to adult stem cells, autologous fibroblasts, platelets and hematopoietic stem cells; by means of non-viral vectors; or through the repair of mutations by chimeric oligonucleotides. In hemophilia, cell therapy approaches have been based mainly on transplantation of healthy cells (adult stem cells or induced pluripotent cell-derived progenitor cells) in order to restore alterations in coagulation factor expression. PMID:23237078

  15. Monoclonal antibodies-based treatment in gastric cancer: current status and future perspectives.

    PubMed

    Roviello, Giandomenico; Polom, Karol; Petrioli, Roberto; Marano, Luigi; Marrelli, Daniele; Paganini, Giovanni; Savelli, Vinno; Generali, Daniele; De Franco, Lorenzo; Ravelli, Andrea; Roviello, Franco

    2016-01-01

    Gastric cancer (GC) is the second leading cause of cancer-related death, and despite having improved treatment modalities over the last decade, for most patients, only modest improvements have been seen in overall survival. Recent progress in understanding the molecular biology of GC and the related signaling pathways offers, from the clinical point of view, promising advances for selected groups of patients. In the past, targeted therapies have significantly impacted the treatment strategy of several common solid tumors such as breast, colorectal, and lung cancers. Unfortunately, translational and clinical research shows fewer encouraging targeted treatments with regards to the GC. To date, only two monoclonal antibodies (mAb), named trastuzumab and ramucirumab, are approved for the treatment of advanced GC, suggesting that in GC, maybe more than in other cancers, effective targeted therapy requires patient selection based on precise predictive molecular biomarkers. The aim of this review is to summarize the available data on the clinical advantages offered by the use of mAbs in the treatment of advanced/metastatic GC. Future perspective is also discussed.

  16. Strategies for diagnosis and treatment of iatrogenic tracheal ruptures.

    PubMed

    Deja, M; Menk, M; Heidenhain, C; Spies, C D; Heymann, A; Weidemann, H; Branscheid, D; Weber-Carstens, S

    2011-12-01

    Management of tracheal ruptures in critically ill patients is challenging. Conservative treatment has been described, but in mechanically ventilated patients with distal tracheal ruptures surgical repair might be inevitable. Strategies for diagnosis and treatment of tracheal ruptures and handling of mechanical ventilation remain to be clarified. Our aim was to comprise a structured diagnostic and treatment protocol for patients suspicious of tracheal injury, including detailed principles of mechanical ventilation and specific indications for conservative or surgical treatment. Patients with tracheal ruptures were compared in accordance to the need of mechanical ventilation and to indication for surgical repair. In patients suffering from tracheal ruptures affecting the whole tracheal wall and with protrusion of mediastinal structures into the lumen surgery was indicated. We compared ventilatory, hemodynamic and clinical parameters between the different patient groups. We report our structured approach in diagnostics and treatment of tracheal ruptures and place special emphasis on respiratory management. Seventeen patients with tracheal rupture were identified. In 8 patients surgical repair was performed 1.8±1.5 days after diagnosis. Previous to surgery, ventilation parameters improved significantly: plateau pressure decreased, percentage of assisted spontaneous breathing increased and compliance improved. Conservative treatment was successful in long-term ventilated patients (13.7±8 days) even when suffering from distal lesions. Invasiveness of mechanical ventilation and obstruction of tracheal lumen might indicate conservative or surgical treatment strategies in long-term ventilated patients suffering from iatrogenic tracheal rupture. Indications for surgical repair remain to be further clarified.

  17. Rehabilitating antisocial personalities: treatment through self-governance strategies.

    PubMed

    McRae, Leon

    2013-02-01

    Offenders with antisocial personality disorder (ASPD) are widely assumed to reject psychotherapeutic intervention. Some commentators, therefore, argue that those with the disorder are better managed in the criminal justice system, where, following the introduction of indeterminate sentences, engagement with psychological treatment is coercively linked to the achievement of parole. By comparison, National Institute of Clinical Excellence guidelines on the management and treatment of ASPD recommend that those who are treatment seeking should be considered for admission to specialist psychiatric hospitals. The rationale is that prison-based interventions are underresourced, and the treatment of ASPD is underprioritised. The justification is that offenders with ASPD can be rehabilitated, if they are motivated. One problem, however, is that little is known about why offenders with ASPD seek treatment or what effect subsequent treatment has on their self-understanding. The aim of this paper is to address these unresolved issues. It draws on the findings of Economic and Social Research Council (ESRC) funded qualitative study examining the experiences of sentenced male offenders admitted to a specialist personality disorder ward within the medium secure estate and the medical practitioners who treat them. The data are analysed with reference to Michel Foucault's work on governmentality and strategy in power relations. Two arguments are advanced: first, offenders with ASPD are motivated by legal coercive pressures to implement a variety of Foucauldian-type strategies to give the false impression of treatment progress. Second, and related, treatment does not result in changes in self-understanding in the resistive client with ASPD. This presupposes that, in respect of this group at least, Foucault was mistaken in his claim that resistive behaviours merely mask the effectiveness of treatment norms over time. Nevertheless, the paper concludes that specialist treatment in the

  18. Rehabilitating antisocial personalities: treatment through self-governance strategies

    PubMed Central

    McRae, Leon

    2012-01-01

    Offenders with antisocial personality disorder (ASPD) are widely assumed to reject psychotherapeutic intervention. Some commentators, therefore, argue that those with the disorder are better managed in the criminal justice system, where, following the introduction of indeterminate sentences, engagement with psychological treatment is coercively linked to the achievement of parole. By comparison, National Institute of Clinical Excellence guidelines on the management and treatment of ASPD recommend that those who are treatment seeking should be considered for admission to specialist psychiatric hospitals. The rationale is that prison-based interventions are underresourced, and the treatment of ASPD is underprioritised. The justification is that offenders with ASPD can be rehabilitated, if they are motivated. One problem, however, is that little is known about why offenders with ASPD seek treatment or what effect subsequent treatment has on their self-understanding. The aim of this paper is to address these unresolved issues. It draws on the findings of Economic and Social Research Council (ESRC) funded qualitative study examining the experiences of sentenced male offenders admitted to a specialist personality disorder ward within the medium secure estate and the medical practitioners who treat them. The data are analysed with reference to Michel Foucault's work on governmentality and strategy in power relations. Two arguments are advanced: first, offenders with ASPD are motivated by legal coercive pressures to implement a variety of Foucauldian-type strategies to give the false impression of treatment progress. Second, and related, treatment does not result in changes in self-understanding in the resistive client with ASPD. This presupposes that, in respect of this group at least, Foucault was mistaken in his claim that resistive behaviours merely mask the effectiveness of treatment norms over time. Nevertheless, the paper concludes that specialist treatment in the

  19. Disease-modifying therapy in multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy: common and divergent current and future strategies

    PubMed Central

    Melzer, N; Meuth, S G

    2014-01-01

    Multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represent chronic, autoimmune demyelinating disorders of the central and peripheral nervous system. Although both disorders share some fundamental pathogenic elements, treatments do not provide uniform effects across both disorders. We aim at providing an overview of current and future disease-modifying strategies in these disorders to demonstrate communalities and distinctions. Intravenous immunoglobulins (IVIG) have demonstrated short-and long-term beneficial effects in CIDP but are not effective in MS. Dimethyl fumarate (BG-12), teriflunomide and laquinimod are orally administered immunomodulatory drugs that are already approved or likely to be approved in the near future for the basic therapy of patients with relapsing–remitting MS (RRMS) due to positive results in Phase III clinical trials. However, clinical trials with these drugs in CIDP have not (yet) been initiated. Natalizumab and fingolimod are approved for the treatment of RRMS, and trials to evaluate their safety and efficacy in CIDP are now planned. Alemtuzumab, ocrelizumab and daclizumab respresent monoclonal antibodies in advanced stages of clinical development for their use in RRMS patients. Attempts to study the safety and efficacy of alemtuzumab and B cell-depleting anti-CD20 antibodies, i.e. rituximab, ocrelizumab or ofatumumab, in CIDP patients are currently under way. We provide an overview of the mechanism of action and clinical data available on disease-modifying immunotherapy options for MS and CIDP. Enhanced understanding of the relative effects of therapies in these two disorders may aid rational treatment selection and the development of innovative treatment approaches in the future. PMID:24032475

  20. Climate Change: A Future of Less Water and More people - Strategies for a Water Constrained World

    NASA Astrophysics Data System (ADS)

    Nahai, D.

    2010-12-01

    Today, the fact that the Earth is warming is indisputable. The evidence of climate change is already all around us, with the occurence of ever more intense weather events, droughts, heat waves, floods and sea level rise. Predictions of greater calamities in the future without swift action must be taken seriously. However, while international summits have focused on means to reduce greenhouse gas emissions, these are largely strategies of containment, not of cure. Even if emissions were to cease today, the current effects of climate change would remain with us for millenia. This is clear from the 2007 report of the Intergovernmental Panel on Climate Change. The world must not only tackle the causes of global warming; it must adapt to the damage already done. This need is most acute where water supply is concerned. The world already faces daunting chalenges. According to United Nations' reports, even today 1.8 million children under 5 die from water related diseases every year; 900 million people lack access to safe drinking water; and 2.6 billion go without basic sanitation. In the developing world, 90% of sewage is discharged to water bodies without adequate treatment contributing to "dead zones". Population increases will make matters worse (an addition of around 3 billion people by 2050 is expected) and climate change will compound the crisis. It is forecast that, as the Earth warms, deserts will expand and droughts will intensify causing demographic shifts even as the world's population burgeons. We are already seeing different regions react to water shortages. Many countries are pursuing seawater desalination. However, seawater desalination has numerous drawbacks; it remains the most expensive of water treatment options and the most energy intensive. Some societies may have no choice but to turn to the sea; others should look to other alternatives first. Such frontrunners could include: (1) enhanced conservation, utilizing public education programs, price

  1. Practical Strategies for Enhancing Adherence to Treatment Regimen in Inflammatory Bowel Disease

    PubMed Central

    Greenley, Rachel N.; Kunz, Jennifer H.; Walter, Jennifer; Hommel, Kevin A.

    2013-01-01

    Promoting adherence to treatment among pediatric and adult patients with inflammatory bowel disease (IBD) is a critical yet challenging task for health care providers. Several existing interventions to enhance adherence among individuals with IBD offer useful information about practical strategies to enhance adherence. The current review article has 3 goals. First, the review provides a context for understanding treatment regimen adherence in IBD by reviewing key definitional, measurement, and conceptual challenges in this area. Next, published studies focused on interventions to enhance adherence in IBD are briefly summarized, followed by a synthesis of practical adherence promotion strategies for use in IBD by health care providers. Strategies are distinguished by the level of evidence supporting their utility as well as by age group. Finally, recommendations for future research to facilitate the development and implementation of practical, evidence-based strategies for adherence promotion in IBD are provided. Findings from the literature review suggest that strategies including education, regimen simplification, and use of reminder systems and organizational strategies (e.g., pill boxes) are likely to be best suited for addressing accidental nonadherence. In contrast, addressing motivational issues, teaching problem-solving skills, and addressing problematic patterns of family functioning are more likely to benefit individuals displaying intentional nonadherence. PMID:23635715

  2. Practical strategies for enhancing adherence to treatment regimen in inflammatory bowel disease.

    PubMed

    Greenley, Rachel N; Kunz, Jennifer H; Walter, Jennifer; Hommel, Kevin A

    2013-06-01

    Promoting adherence to treatment among pediatric and adult patients with inflammatory bowel disease (IBD) is a critical yet challenging task for health care providers. Several existing interventions to enhance adherence among individuals with IBD offer useful information about practical strategies to enhance adherence. The current review article has 3 goals. First, the review provides a context for understanding treatment regimen adherence in IBD by reviewing key definitional, measurement, and conceptual challenges in this area. Next, published studies focused on interventions to enhance adherence in IBD are briefly summarized, followed by a synthesis of practical adherence promotion strategies for use in IBD by health care providers. Strategies are distinguished by the level of evidence supporting their utility as well as by age group. Finally, recommendations for future research to facilitate the development and implementation of practical, evidence-based strategies for adherence promotion in IBD are provided. Findings from the literature review suggest that strategies including education, regimen simplification, and use of reminder systems and organizational strategies (e.g., pill boxes) are likely to be best suited for addressing accidental nonadherence. In contrast, addressing motivational issues, teaching problem-solving skills, and addressing problematic patterns of family functioning are more likely to benefit individuals displaying intentional nonadherence.

  3. Strategies to reduce indoor tanning: current research gaps and future opportunities for prevention.

    PubMed

    Holman, Dawn M; Fox, Kathleen A; Glenn, Jeffrey D; Guy, Gery P; Watson, Meg; Baker, Katie; Cokkinides, Vilma; Gottlieb, Mark; Lazovich, DeAnn; Perna, Frank M; Sampson, Blake P; Seidenberg, Andrew B; Sinclair, Craig; Geller, Alan C

    2013-06-01

    Exposure to ultraviolet radiation from indoor tanning device use is associated with an increased risk of skin cancer, including risk of malignant melanoma, and is an urgent public health problem. By reducing indoor tanning, future cases of skin cancer could be prevented, along with the associated morbidity, mortality, and healthcare costs. On August 20, 2012, the CDC hosted a meeting to discuss the current body of evidence on strategies to reduce indoor tanning as well as research gaps. Using the Action Model to Achieve Healthy People 2020 Overarching Goals as a framework, the current paper provides highlights on the topics that were discussed, including (1) the state of the evidence on strategies to reduce indoor tanning; (2) the tools necessary to effectively assess, monitor, and evaluate the short- and long-term impact of interventions designed to reduce indoor tanning; and (3) strategies to align efforts at the national, state, and local levels through transdisciplinary collaboration and coordination across multiple sectors. Although many challenges and barriers exist, a coordinated, multilevel, transdisciplinary approach has the potential to reduce indoor tanning and prevent future cases of skin cancer.

  4. Design of Sequentially Randomized Trials for Testing Adaptive Treatment Strategies

    PubMed Central

    Ogbagaber, Semhar B.; Karp, Jordan; Wahed, Abdus S.

    2016-01-01

    An adaptive treatment strategy (ATS) is an outcome-guided algorithm that allows personalized treatment of complex diseases based on patients’ disease status and treatment history. Conditions such as AIDS, depression, and cancer usually require several stages of treatment due to the chronic, multifactorial nature of illness progression and management. Sequential multiple assignment randomized (SMAR) designs permit simultaneous inference about multiple ATSs, where patients are sequentially randomized to treatments at different stages depending upon response status. The purpose of the article is to develop a sample size formula to ensure adequate power for comparing two or more ATSs. Based on a Wald-type statistic for comparing multiple ATSs with a continuous endpoint, we develop a sample size formula and test it through simulation studies. We show via simulation that the proposed sample size formula maintains the nominal power. The proposed sample size formula is not applicable to designs with time-to-event endpoints but the formula will be useful for practitioners while designing SMAR trials to compare adaptive treatment strategies. PMID:26412033

  5. Evaluation of treatment strategies for muscle function in infants with congenital muscular torticollis.

    PubMed

    Ohman, Anna; Mårdbrink, Eva-Lott; Stensby, Jennie; Beckung, Eva

    2011-10-01

    This study focuses on the treatment of the muscle function imbalance and asymmetric head posture for infants with congenital muscular torticollis (CMT). The aim of this study was to compare treatment time for groups with different strategies for muscle function training. The treatment goal was to achieve a symmetric head posture. Thirty-seven infants were randomised to three groups. Group I was treated only with handling strategies. Group II got the same handling strategies but also received specific strength exercises. Group III received the same treatment as group II but was also provided with weekly training by a physiotherapist. Mean age at the start of treatment was 4.5 months of age, range 1-10.5. The possible effect of covariates was also investigated; age at the start of treatment, range of motion (ROM) in rotation of the neck, ROM in lateral flexion of the neck, the muscle function scale (MFS) score, plagiocephaly, and gender were analysed with ANCOVA. Thirty-one treated infants achieved symmetric head posture before the age of 12 months. Mean treatment time (3.5 month) did not differ significantly between the groups. All infants randomised to group I could stay in that group. The MFS score and age at the start of the treatment influenced treatment time (p < 0.05). The treatment time for all groups was similar. Early referral to physical therapy of infants with CMT and muscle function imbalance in lateral righting could shorten treatment time. Studies about natural course and long-term effects of muscular imbalance must be investigated in future research.

  6. Multimodality treatment strategies have changed prognosis of peritoneal metastases

    PubMed Central

    Lungoci, Corneliu; Mironiuc, Aurel Ion; Muntean, Valentin; Oniu, Traian; Leebmann, Hubert; Mayr, Max; Piso, Pompiliu

    2016-01-01

    For a long time, treatment of peritoneal metastases (PM) was mostly palliative and thus, this status was link with “terminal status/despair”. The current multimodal treatment strategy, consisting of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), has been strenuously achieved over time, but seems to be the best treatment option for PM patients. As we reviewed the literature data, we could emphasize some milestones and also, controversies in the history of proposed multimodal treatment and thus, outline the philosophy of this approach, which seems to be an unusual one indeed. Initially marked by nihilism and fear, but benefiting from a remarkable joint effort of human and material resources (multi-center and -institutional research), over a period of 30 years, CRS and HIPEC found their place in the treatment of PM. The next 4 years were dedicated to the refinement of the multimodal treatment, by launching research pathways. In selected patients, with requires training, it demonstrated a significant survival results (similar to the Hepatic Metastases treatment), with acceptable risks and costs. The main debates regarding CRS and HIPEC treatment were based on the oncologists’ perspective and the small number of randomized clinical trials. It is important to statement the PM patient has the right to be informed of the existence of CRS and HIPEC, as a real treatment resource, the decision being made by multidisciplinary teams. PMID:26798438

  7. Future Dietitian 2025: informing the development of a workforce strategy for dietetics.

    PubMed

    Hickson, M; Child, J; Collinson, A

    2017-09-21

    Healthcare is changing and the professions that deliver it need to adapt and change too. The aim of this research was to inform the development of a workforce strategy for Dietetics for 2020-2030. This included an understanding of the drivers for change, the views of stakeholders and recommendations to prepare the profession for the future. The research included three phases: (i) establishing the context which included a literature and document review (environmental scan); (ii) discovering the profession and professional issues using crowd-sourcing technology; and (iii) articulating the vision for the future using appreciative inquiry. The environmental scan described the current status of the dietetic profession, the changing healthcare environment, the context in which dietitians work and what future opportunities exist for the profession. The online conversation facilitated by crowd-sourcing technology asked the question: 'How can dietitians strengthen their future role, influence and impact?' Dietitians and interested stakeholders (726 and 109, respectively) made 6130 contributions. Seven priorities were identified and fed into the appreciative inquiry event. The event bought together 54 dietitians and analysis of the discussions generated five themes: (i) professional identity; (ii) strong foundations-creating structure and direction for the profession; (iii) amplifying visibility and influence; (iv) embracing advances in science and technology; and (v) career advancement and emerging opportunities. A series of recommendations were made for the next steps in moving the workforce to a new future. The future for dietetics looks bright, embracing technology, as well as exploring different ways of working and new opportunities, as this dynamic profession continues to evolve. © 2017 The British Dietetic Association Ltd.

  8. Immunotherapeutic strategies in the treatment of HIV infection and AIDS.

    PubMed

    Birx, D L; Redfield, R R

    1993-08-01

    The immune response against HIV does not result in complete viral clearance. Recent interventions have focused on novel strategies to modify human anti-HIV immunity. Active vaccination of patients with HIV infection (vaccine therapy) safely alters the immune repertoire against HIV. This unique approach will provide insight into the immunoregulatory consequences of HIV-specific innate and adaptive immune responses, and hopefully define the immunological Achilles heel of HIV. Once defined, researchers, aided by current biotechnological techniques, can rationally design future vaccines and immune based therapeutic products.

  9. Adherence to Continuous Positive Airway Pressure Treatment for Obstructive Sleep Apnea: Implications for Future Interventions

    PubMed Central

    Weaver, Terri E.; Sawyer, Amy M.

    2010-01-01

    Adherence to continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea (OSA) is a critical problem with adherence rates ranging from 30–60%. Poor adherence to CPAP is widely recognized as a significant limiting factor in treating OSA, reducing the overall effectiveness of the treatment and leaving many OSA patients at heightened risk for comorbid conditions, impaired function and quality of life. The extant literature examining adherence to CPAP provides critical insight to measuring adherence outcomes, defining optimal adherence levels, and predicting CPAP adherence. This research has revealed salient factors that are associated with or predict CPAP adherence and may guide the development of interventions to promote CPAP adherence. Over the past 10 years, intervention studies to promote CPAP adherence have incorporated a multitude of strategies including education, support, cognitive behavioral approaches, and mixed strategies. This review of the current state of science of CPAP adherence will (1) synthesize the extant literature with regard to measuring, defining, and predicting CPAP adherence, (2) review published intervention studies aimed at promoting CPAP adherence, and (3) suggest directions for future empiric study of adherence to CPAP that will have implications for translational science. Our current understanding of CPAP adherence suggests that adherence is a multi-factorial, complex clinical problem that requires similarly designed approaches to effectively address poor CPAP adherence in the OSA population. PMID:20308750

  10. Glucagon-Like Peptide-1 Formulation--the Present and Future Development in Diabetes Treatment.

    PubMed

    Lee, Chooi Yeng

    2016-03-01

    Type 2 diabetes mellitus is a chronic metabolic disorder that has become the fourth leading cause of death in the developed countries. The disorder is characterized by pancreatic β-cells dysfunction, which causes hyperglycaemia leading to several other complications. Treatment by far, which focuses on insulin administration and glycaemic control, has not been satisfactory. Glucagon-like peptide-1 (GLP1) is an endogenous peptide that stimulates post-prandial insulin secretion. Despite being able to mimic the effect of insulin, GLP1 has not been the target drug in diabetes treatment due to the peptide's metabolic instability. After a decade-long effort to improve the pharmacokinetics of GLP1, a number of GLP1 analogues are currently available on the market. The current Minireview does not discuss these drugs but presents strategies that were undertaken to address the weaknesses of the native GLP1, particularly drug delivery techniques used in developing GLP1 nanoparticles and modified GLP1 molecule. The article highlights how each of the selected preparations has improved the efficacy of GLP1, and more importantly, through an overview of these studies, it will provide an insight into strategies that may be adopted in the future in the development of a more effective oral GLP1 formulation.

  11. Bio-nano hybrid materials based on bacteriorhodopsin: Potential applications and future strategies.

    PubMed

    Mahyad, Baharak; Janfaza, Sajjad; Hosseini, Elaheh Sadat

    2015-11-01

    This review presents an overview of recent progress in the development of bio-nano hybrid materials based on the photoactive protein bacteriorhodopsin (bR). The interfacing of bR with various nanostructures including colloidal nanoparticles (such as quantum dots and Ag NPs) and nanoparticulate thin films (such as TiO2 NPs and ZnO NPs,) has developed novel functional materials. Applications of these materials are comprehensively reviewed in two parts: bioelectronics and solar energy conversion. Finally, some perspectives on possible future strategies in bR-based nanostructured devices are presented.

  12. Polymeric Nanocomposite Membranes for Next Generation Pervaporation Process: Strategies, Challenges and Future Prospects

    PubMed Central

    Singha, Nayan Ranjan

    2017-01-01

    Pervaporation (PV) has been considered as one of the most active and promising areas in membrane technologies in separating close boiling or azeotropic liquid mixtures, heat sensitive biomaterials, water or organics from its mixtures that are indispensable constituents for various important chemical and bio-separations. In the PV process, the membrane plays the most pivotal role and is of paramount importance in governing the overall efficiency. This article evaluates and collaborates the current research towards the development of next generation nanomaterials (NMs) and embedded polymeric membranes with regard to its synthesis, fabrication and application strategies, challenges and future prospects. PMID:28885591

  13. Therapeutic strategies in Sickle Cell Anemia: The past present and future.

    PubMed

    Fernandes, Queenie

    2017-06-01

    Sickle Cell Anemia (SCA) was one of the first hemoglobinopathies to be discovered. It is distinguished by the mutation-induced expression of a sickle cell variant of hemoglobin (HbS) that triggers erythrocytes to take a characteristic sickled conformation. The complex physiopathology of the disease and its associated clinical complications has initiated multi-disciplinary research within its field. This review attempts to lay emphasis on the evolution, current standpoint and future scope of therapeutic strategies in SCA. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Alternative futures: Fields, boundaries, and divergent professionalisation strategies within the Chiropractic profession.

    PubMed

    Brosnan, Caragh

    2017-08-19

    Sociological studies of the complementary and alternative medicine (CAM) occupations have documented the professionalisation strategies these groups use to establish boundaries between themselves and their competitors, including seeking educational accreditation and statutory regulation/licensure. Chiropractic has been particularly successful at professionalising and in Australia and the UK it is taught within public universities. Recent events have threatened chiropractic's university foothold, however, showing that professionalisation needs to be understood as an ongoing process of negotiation. Based on interviews with chiropractors in Australia and the UK, this paper examines the professionalisation strategies deployed by chiropractors within and outside of the university. Highly divergent strategies are identified across different sectors of the profession, relating to defining the chiropractic paradigm, directing education and constructing professional identity. In each domain, chiropractic academics tended to prioritise building the evidence base and becoming more aligned with medicine and other allied health professions. Although some practitioners supported this agenda, others strove to preserve chiropractic's vitalistic philosophy and professional distinction. Following Bourdieu, these intra-professional struggles are interpreted as occurring within a field in which chiropractors compete for different forms of capital, pulled by two opposing poles. The differing orientations and strategies pursued at the two poles of the field point to a number of possible futures for this CAM profession, including a potential split within the profession itself. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Cancer Treatment-Related Cardiotoxicity: Understanding the Current State of Knowledge and Developing Future Research Priorities

    Cancer.gov

    Cancer Treatment-Related Cardiotoxicity: Understanding the Current State of Knowledge and Developing Future Research Priorities, a 2013 workshop sponsored by the Epidemiology and Genomics Research Program.

  16. Treatment of B-cell chronic lymphocytic leukaemia: current status and future perspectives.

    PubMed

    Montserrat, E; Bosch, F; Rozman, C

    1997-01-01

    In the last two decades, important advances have been made in the biology, natural history, and prognosis of B-cell chronic lymphocytic leukaemia (CLL). In addition, treatment possibilities for patients with CLL have changed as a result of the identification of prognostic factors for survival and the availability of new drugs and treatment strategies. Patients in the early clinical stages (Binet A, Rai 0) with stable disease have a probability of long survival and should not be treated unless the disease progresses. In contrast, most patients with poor prognostic features, such as an advanced clinical stage (Binet B, C; Rai III, IV), diffuse bone-marrow infiltration or rapidly increasing blood lymphocyte levels, have a median survival probability of < 5 years and require therapy. Purine analogues are highly effective. Among these, fludarabine has become the treatment of choice for patients failing standard therapies. The role of purine analogues either alone or in combination with other drugs as front-line therapy is being investigated. Certain situations (e.g. autoimmune cytopenias, hypersplenism) require special treatment approaches (e.g. corticosteroids, splenectomy). Transplants of progenitor haematopoietic cells are also increasingly performed and deserve further investigation in younger patients with poor prognostic features. As a result of these advances, symptoms palliation is no longer the only possible goal in CLL therapy; sustained remissions and even cures are likely to be obtained in the near future.

  17. Therapeutic Effects of Traditional Chinese Medicine on Spinal Cord Injury: A Promising Supplementary Treatment in Future.

    PubMed

    Zhang, Qian; Yang, Hao; An, Jing; Zhang, Rui; Chen, Bo; Hao, Ding-Jun

    2016-01-01

    Objective. Spinal cord injury (SCI) is a devastating neurological disorder caused by trauma. Pathophysiological events occurring after SCI include acute, subacute, and chronic phases, while complex mechanisms are comprised. As an abundant source of natural drugs, Traditional Chinese Medicine (TCM) attracts much attention in SCI treatment recently. Hence, this review provides an overview of pathophysiology of SCI and TCM application in its therapy. Methods. Information was collected from articles published in peer-reviewed journals via electronic search (PubMed, SciFinder, Google Scholar, Web of Science, and CNKI), as well as from master's dissertations, doctoral dissertations, and Chinese Pharmacopoeia. Results. Both active ingredients and herbs could exert prevention and treatment against SCI, which is linked to antioxidant, anti-inflammatory, neuroprotective, or antiapoptosis effects. The detailed information of six active natural ingredients (i.e., curcumin, resveratrol, epigallocatechin gallate, ligustrazine, quercitrin, and puerarin) and five commonly used herbs (i.e., Danshen, Ginkgo, Ginseng, Notoginseng, and Astragali Radix) was elucidated and summarized. Conclusions. As an important supplementary treatment, TCM may provide benefits in repair of injured spinal cord. With a general consensus that future clinical approaches will be diversified and a combination of multiple strategies, TCM is likely to attract greater attention in SCI treatment.

  18. Therapeutic Effects of Traditional Chinese Medicine on Spinal Cord Injury: A Promising Supplementary Treatment in Future

    PubMed Central

    Zhang, Qian; Yang, Hao; An, Jing; Zhang, Rui; Chen, Bo; Hao, Ding-Jun

    2016-01-01

    Objective. Spinal cord injury (SCI) is a devastating neurological disorder caused by trauma. Pathophysiological events occurring after SCI include acute, subacute, and chronic phases, while complex mechanisms are comprised. As an abundant source of natural drugs, Traditional Chinese Medicine (TCM) attracts much attention in SCI treatment recently. Hence, this review provides an overview of pathophysiology of SCI and TCM application in its therapy. Methods. Information was collected from articles published in peer-reviewed journals via electronic search (PubMed, SciFinder, Google Scholar, Web of Science, and CNKI), as well as from master's dissertations, doctoral dissertations, and Chinese Pharmacopoeia. Results. Both active ingredients and herbs could exert prevention and treatment against SCI, which is linked to antioxidant, anti-inflammatory, neuroprotective, or antiapoptosis effects. The detailed information of six active natural ingredients (i.e., curcumin, resveratrol, epigallocatechin gallate, ligustrazine, quercitrin, and puerarin) and five commonly used herbs (i.e., Danshen, Ginkgo, Ginseng, Notoginseng, and Astragali Radix) was elucidated and summarized. Conclusions. As an important supplementary treatment, TCM may provide benefits in repair of injured spinal cord. With a general consensus that future clinical approaches will be diversified and a combination of multiple strategies, TCM is likely to attract greater attention in SCI treatment. PMID:27118982

  19. Treatment strategy for tibial plateau fractures: an update

    PubMed Central

    Prat-Fabregat, Salvi; Camacho-Carrasco, Pilar

    2016-01-01

    Tibial plateau fractures are complex injuries produced by high- or low-energy trauma. They principally affect young adults or the ‘third age’ population. These fractures usually have associated soft-tissue lesions that will affect their treatment. Sequential (staged) treatment (external fixation followed by definitive osteosynthesis) is recommended in more complex fracture patterns. But one should remember that any type of tibial plateau fracture can present with soft-tissue complications. Typically the Schatzker or AO/OTA classification is used, but the concept of the proximal tibia as a three-column structure and the detailed study of the posteromedial and posterolateral fragment morphology has changed its treatment strategy. Limb alignment and articular surface restoration, allowing early knee motion, are the main goals of surgical treatment. Partially articular factures can be treated by minimally-invasive methods and arthroscopy is useful to assist and control the fracture reduction and to treat intra-articular soft-tissue injuries. Open reduction and internal fixation (ORIF) is the gold standard treatment for these fractures. Complex articular fractures can be treated by ring external fixators and minimally-invasive osteosynthesis (EFMO) or by ORIF. EFMO can be related to suboptimal articular reduction; however, outcome analysis shows results that are equal to, or even superior to, ORIF. The ORIF strategy should also include the optimal reduction of the articular surface. Anterolateral and anteromedial surgical approaches do not permit adequate reduction and fixation of posterolateral and posteromedial fragments. To achieve this, it is necessary to reduce and fix them through specific posterolateral or posteromedial approaches that allow optimal reduction and plate/screw placement. Some authors have also suggested that primary total knee arthroplasty could be an option in specific patients and with specific fracture patterns. Cite this article: Prat

  20. Mandibular Subcondylar Fractures: A Review on Treatment Strategies

    PubMed Central

    Bayat, Mohammad; Parvin, Milad; Meybodi, Ali Aghaei

    2016-01-01

    Condylar injuries are often subjected to discussion and controversy in maxillofacial surgery as they constitute many of the facial fractures. The condylar area has a great clinical value due to its important components. Vital components in this area are susceptible to functional disability due to either the fracture itself or the subsequent surgical intervention. Each of the strategies for the management of these fractures has its advantages and disadvantages. As there are controversies around management of condylar fractures, different treatment modalities are suggested in literature, so this paper reviews different treatment strategies of the following types of fractures in adults: 1-Closed reduction with maxillomandibular fixation, 2-Open reduction with internal fixation, 3-Endoscopic-assisted reduction with internal fixation. In conclusion, we declare that the endoscopic surgery is certainly a good replacement for approaches through the skin, for subcondylar fractures, but still more randomized clinical trials are needed to be carried out on this issue. PMID:27957317

  1. Reducing Fatal Opioid Overdose: Prevention, Treatment and Harm Reduction Strategies.

    PubMed

    Hawk, Kathryn F; Vaca, Federico E; D'Onofrio, Gail

    2015-09-01

    The opioid overdose epidemic is a major threat to the public's health, resulting in the development and implementation of a variety of strategies to reduce fatal overdose. Many strategies are focused on primary prevention and increased access to effective treatment, although the past decade has seen an exponential increase in harm reduction initiatives. To maximize identification of opportunities for intervention, initiatives focusing on prevention, access to effective treatment, and harm reduction are examined independently, although considerable overlap exists. Particular attention is given to harm reduction approaches, as increased public and political will have facilitated widespread implementation of several initiatives, including increased distribution of naloxone and policy changes designed to increase bystander assistance during a witnessed overdose.

  2. Reducing Fatal Opioid Overdose: Prevention, Treatment and Harm Reduction Strategies

    PubMed Central

    Hawk, Kathryn F.; Vaca, Federico E.; D’Onofrio, Gail

    2015-01-01

    The opioid overdose epidemic is a major threat to the public’s health, resulting in the development and implementation of a variety of strategies to reduce fatal overdose [1-3]. Many strategies are focused on primary prevention and increased access to effective treatment, although the past decade has seen an exponential increase in harm reduction initiatives. To maximize identification of opportunities for intervention, initiatives focusing on prevention, access to effective treatment, and harm reduction are examined independently, although considerable overlap exists. Particular attention is given to harm reduction approaches, as increased public and political will have facilitated widespread implementation of several initiatives, including increased distribution of naloxone and policy changes designed to increase bystander assistance during a witnessed overdose [4-7]. PMID:26339206

  3. Current Antiplatelet Treatment Strategy in Patients with Diabetes Mellitus

    PubMed Central

    Jung, Jung Hwa; Tantry, Udaya S.; Gurbel, Paul A.

    2015-01-01

    Patients with diabetes mellitus (DM) have accelerated atherosclerosis with an increased risk for atherothrombotic cardiovascular complications. A state of high platelet reactivity and activation, hypercoagulability (prothrombotic state) and a subdued response to standard antiplatelet agents may explain high rate of adverse cardiovascular events in patients with DM. Several antithrombotic treatment strategies have been developed to control the prothrombotic state in patients with DM: dose modification of commonly used agents; use of potent agents; and addition of a third antithrombotic drug (triple therapy) to commonly prescribed dual antiplatelet therapy of aspirin and a P2Y12 inhibitor. The present review aims to provide an overview of the current knowledge on platelet abnormalities in patients with DM, focusing on the challenges and perspectives of antiplatelet treatment strategies in this population. PMID:25922803

  4. Pharmacokinetic strategies for treatment of drug overdose and addiction

    PubMed Central

    Gorelick, David A

    2012-01-01

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

  5. Pharmacokinetic strategies for treatment of drug overdose and addiction.

    PubMed

    Gorelick, David A

    2012-02-01

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

  6. Assessment and treatment strategies for rotator cuff tears

    PubMed Central

    Al-Hakim, Wisam; Noorani, Ali

    2014-01-01

    Tears of the rotator cuff are common and becoming an increasingly frequent problem. There is a vast amount of literature on the merits and limitations of the various methods of clinical and radiological assessment of rotator cuff tears. This is also the case with regard to treatment strategies. Certain popular beliefs and principles practiced widely and the basis upon which they are derived may be prone to inaccuracy. We provide an overview of the historical management of rotator cuff tears, as well as an explanation for how and why rotator cuff tears should be managed, and propose a structured methodology for their assessment and treatment. PMID:27582960

  7. Modern treatment strategies for patients with epilepsy: a review.

    PubMed Central

    Duncan, J S

    1991-01-01

    Of patients who develop epilepsy 70-80% will become seizure free, the remaining 20% are the most difficult to treat satisfactorily. Eighty per cent of patients are best treated with a single drug. Stepwise treatment plans for the treatment of newly diagnosed patients and for the evaluation of patients with chronic epilepsy are suggested. There is a lack of consensus regarding the rate at which to taper antiepileptic drugs being discontinued in patients with active epilepsy. There are arguments for making drug changes rapidly; these arguments and strategies for managing the withdrawal of individual drugs are presented. PMID:2013897

  8. Treatment strategies in early and advanced Parkinson disease.

    PubMed

    Ossig, Christiana; Reichmann, Heinz

    2015-02-01

    The initiation of therapy in Parkinson disease (PD), altering the medication, adding new substances, and switching to alternative therapies throughout the disease is always a matter of debate. In the past, experts in PD have propagated different medication strategies. Even though there is no new medical treatment on the horizon, much has changed in consideration of the known treatments in the early and advanced therapy for PD. Therapeutic regimens have to be adapted and adjusted on a regular basis to accomplish the best medical care for the predominant symptom of the individual patient with PD. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Therapeutic strategies for the treatment of multiple myeloma.

    PubMed

    Saini, Neeraj; Mahindra, Anuj

    2013-04-01

    The outcome of patients with myeloma has improved significantly in the past decade with the incorporation of the immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor, bortezomib. Considering nearly all patients relapse, myeloma remains an active area of investigation. There are several promising classes of agents including next generation immunomodulatory agents, proteasome inhibitors, antibody and antitumor immunotherapy approaches that are being evaluated. This article provides an overview on the therapeutic strategies in the treatment of multiple myeloma.

  10. [Evolving strategies over time for treatment of breast cancer].

    PubMed

    Roché, Henri

    2013-09-01

    The natural history of breast diseases has changed overtime and successive therapeutic strategies have been adapted accordingly. Recently, biological findings on geno- and phenotypic characteristics of tumor cells offer new basis for the development of treatments that target homogenous and various subtypes of breast cancer. Unfortunately, traditional clinical research tools are not in phase with rapid changes in both biological knowledge of the disease and new targeted agents. New methodological approaches are urgently needed to validate such changes and improvements in prognosis.

  11. Strategy for Testing the Efficacy of Ballast Water Treatment Technologies

    DTIC Science & Technology

    2003-12-01

    Subtitle 5. Report Date STRATEGY FOR TESTING THE EFFICACY OF BALLAST December 2003 WATER TREATMENT TECHNOLOGIES 6. Performing Organization Code ...Report & Period Covered Final U.S. Department of Homeland Security 14. Sponsoring Agency Code United States Coast Guard Commandant (G-MSO) Marine Safety...tree illustrating the complex diversity of ballast water-borne organisms. Phylogenetic information obtained from Woese , 2000 and the Tree of Life Web

  12. Cognitive-behavioral treatment of depression in men: tailoring treatment and directions for future research.

    PubMed

    Spendelow, Jason S

    2015-03-01

    Depression is a significant public health issue and many researchers have suggested that modifications to conventional cognitive-behavioral therapy (CBT) are required to address infrequent help-seeking in men and counter negative effects of traditional masculinity on therapeutic engagement. This narrative review summarizes recommended alterations to CBT in the areas of therapeutic setting, process, and content. Key themes from this literature include a focus on behavioural interventions, and harmful cognitions that orginate from the traditional male gender stereotype. This literature is marked by limited empirical support for many of the recommended treatment modifications, and several options for future research are outlined. © The Author(s) 2014.

  13. Improving Care for Depression & Suicide Risk in Adolescents: Innovative Strategies for Bringing Treatments to Community Settings

    PubMed Central

    Asarnow, Joan Rosenbaum; Miranda, Jeanne

    2015-01-01

    This article reviews the literature on interventions and services for depression and suicide prevention among adolescents, with the goals of placing this science within the context of current changing health care environments and highlighting innovative models for improving health and mental health. We examine the: challenges and opportunities offered by new initiatives and legislation designed to transform the U.S. health and mental healthcare systems; summarize knowledge regarding the treatment of depression and suicidality/self-harm in adolescents; and describe innovative models for partnering with health systems and communities. This review demonstrates that treatment models and service delivery strategies are currently available for increasing evidence-based care, particularly for depression, and concludes with recommendations for future research and quality improvement initiatives aimed at inspiring additional efforts to put science to work, bridge science and community practice, and develop strategies for partnering with communities to improve care, mental health, and well-being among adolescents. PMID:24437432

  14. Use of intervention strategies by assertive community treatment teams to promote patients' engagement.

    PubMed

    Manuel, Jennifer I; Appelbaum, Paul S; Le Melle, Stephanie M; Mancini, Anthony D; Huz, Steve; Stellato, Candice B; Finnerty, Molly T

    2013-06-01

    This study explored the range of interventions and the use of more intrusive techniques by staff of assertive community treatment (ACT) teams to promote engagement, manage problem behaviors, and reinforce positive behaviors among patients. Individual and organizational characteristics that may be associated with these practices were identified. Between January and March 2006, clinicians (N=239) from 34 ACT teams participated in a one-time survey about their intervention strategies with patients, perceptions about the ACT team environment, and beliefs about persons with severe mental illness. Significant variation existed in the types of interventions employed across teams. The less intrusive strategies, including positive inducements and verbal guidance, were the most common. Other strategies that placed limits on patients but that were still considered less intrusive-such as medication monitoring and money management-were also common. Clinicians who reported working in more demoralized climates and having negative perceptions of mental illness were more likely to endorse leveraged or intrusive interventions. The findings of this study suggest significant variation across teams in the use of intervention strategies. Both perceptions of a demoralized organizational climate and stigmatizing beliefs about mental illness were correlated with the use of more intrusive intervention strategies. Future research on the role and appropriateness of more intrusive interventions in mental health treatment and the impact of such interventions on patient outcomes is warranted.

  15. Strategies and techniques to enhance constructed wetland performance for sustainable wastewater treatment.

    PubMed

    Wu, Haiming; Fan, Jinlin; Zhang, Jian; Ngo, Huu Hao; Guo, Wenshan; Liang, Shuang; Hu, Zhen; Liu, Hai

    2015-10-01

    Constructed wetlands (CWs) have been used as an alternative to conventional technologies for wastewater treatment for more than five decades. Recently, the use of various modified CWs to improve treatment performance has also been reported in the literature. However, the available knowledge on various CW technologies considering the intensified and reliable removal of pollutants is still limited. Hence, this paper aims to provide an overview of the current development of CW strategies and techniques for enhanced wastewater treatment. Basic information on configurations and characteristics of different innovations was summarized. Then, overall treatment performance of those systems and their shortcomings were further discussed. Lastly, future perspectives were also identified for specialists to design more effective and sustainable CWs. This information is used to inspire some novel intensifying methodologies, and benefit the successful applications of potential CW technologies.

  16. Optimal First-Line Treatment for Helicobacter pylori Infection: Recent Strategies

    PubMed Central

    2016-01-01

    A new treatment strategy is needed, as the efficacy of triple therapy containing clarithromycin—the current standard treatment for Helicobacter pylori infection—is declining. Increasing antibiotic resistance of H. pylori is the most significant factor contributing to eradication failure. Thus, selecting the most appropriate regimen depending on resistance is optimal, but identifying resistance to specific antibiotics is clinically challenging. In a region suspected to have high clarithromycin resistance, bismuth quadruple therapy and so-called nonbismuth quadruple therapies (sequential, concomitant, and sequential-concomitant hybrid) are some first-line regimen options. However, more research is needed regarding appropriate second-line treatments after first-line treatment failure. Tailored therapy, which is based on antibiotic sensitivity testing, would be optimal but has several limitations for clinical use, and an alternative technique is required. A novel potassium-competitive acid blocker-based eradication regimen could be a valuable eradication option in the near future. PMID:28070184

  17. Large-Scale Cooperative Dissemination of Governmental Information in Emergency — An Experiment and Future Strategies

    NASA Astrophysics Data System (ADS)

    Horiba, Katsuhiro; Okawa, Keiko; Murai, Jun

    On the 11th of March, 2011, a massive earthquake hit the northeast region of Japan. The government of Japan needed to publish information regarding the earthquake and its influences. However, their capacity of Web services overflowed. They called the industry and academia for help for providing stable information service to the people. Industry and academia formed a team to answer the call and named themselves the “EQ project”. This paper describes how the EQ Project was organized and operated, and gives analyses of the statistics. An academic organization took the lead in the EQ Project. Ten organizations which consisted of commercial IT industry and academics specialized in Internet technology, were participating in the EQ Project and they structured the three clusters based on their relationships and technological approach. In WIDE Cluster, one of three clusters in the structure of EQ, the peak number of file accesses per day was over 90 thousand, the mobile browsers was 3.4% and foreign languages (translated contents) were referred 35%. We have also discussed the future information distribution strategies in emergency situation based on the experiences of the EQ Project, and proposed nine suggestions to the MEXT as a future strategy.

  18. Treatment of Early Onset Schizophrenia: Recent Trends, Challenges and Future Considerations

    PubMed Central

    Vyas, Nora S.; Gogtay, Nitin

    2012-01-01

    Early onset schizophrenia (onset before adulthood) is a rare, severe, and chronic form of schizophrenia. The clinical presentation of schizophrenia at this unusually early age of onset has been associated with premorbid developmental abnormalities, poor response to neuroleptic treatment, greater admission rates, and poor prognosis. This is a brief, condensed review of current treatment strategies for the early onset population highlighting the need for novel treatment strategies for these generally treatment-refractory cases. Based on the current literature, second-generation antipsychotics remain the mainstay of treatment, although current medications provide suboptimal response at best. Based on the adult literature, combining antipsychotic treatment with psychotherapeutic intervention may be a more comprehensive treatment strategy. Indeed, early detection, identification of relevant biomarkers, coupled with advancing knowledge of the neurochemical and neuroanatomic pathways may help design informed and novel treatment strategies. PMID:22485097

  19. Immunocytokines for cancer treatment: past, present and future

    PubMed Central

    Neri, Dario; Sondel, Paul M.

    2016-01-01

    Immunocytokines are antibody-cytokine fusion proteins, with the potential to preferentially localize on tumor lesions and to activate anticancer immunity at the site of disease. Various tumor targets (e.g., cell membrane antigens and extracellular matrix components) and antibody formats (e.g., intact IgG and antibody fragments) have been considered for immunocytokine development and some products have advanced to clinical trials. In this review, we present relevant concepts and strategies for the design and use of anticancer immunocytokine products. In addition, we discuss emerging strategies for the pharmaceutical development and clinical application of this promising class of biopharmaceuticals. PMID:27060634

  20. Consensus on Current Injectable Treatment Strategies in the Asian Face.

    PubMed

    Wu, Woffles T L; Liew, Steven; Chan, Henry H; Ho, Wilson W S; Supapannachart, Nantapat; Lee, Hong-Ki; Prasetyo, Adri; Yu, Jonathan Nevin; Rogers, John D

    2016-04-01

    The desire for and use of nonsurgical injectable esthetic facial treatments are increasing in Asia. The structural and anatomical features specific to the Asian face, and differences from Western populations in facial aging, necessitate unique esthetic treatment strategies, but published recommendations and clinical evidence for injectable treatments in Asians are scarce. The Asian Facial Aesthetics Expert Consensus Group met to discuss current practices and consensus opinions on the cosmetic use of botulinum toxin and hyaluronic acid (HA) fillers, alone and in combination, for facial applications in Southeastern and Eastern Asians. Consensus opinions and statements on treatment aims and current practice were developed following discussions regarding pre-meeting and meeting survey outcomes, peer-reviewed literature, and the experts' clinical experience. The indications and patterns of use of injectable treatments vary among patients of different ages, and among Asian countries. The combination use of botulinum toxin and fillers increases as patients age. Treatment aims in Asians and current practice regarding the use of botulinum toxin and HA fillers in the upper, middle, and lower face of patients aged 18 to >55 years are presented. In younger Asian patients, addressing proportion and structural features and deficiencies are important to achieve desired esthetic outcomes. In older patients, maintaining facial structure and volume and addressing lines and folds are essential to reduce the appearance of aging. This paper provides guidance on treatment strategies to address the complex esthetic requirements in Asian patients of all ages. This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

  1. The wave of the future: genetic profiling in treatment selection.

    PubMed

    Ewing, Jennifer C

    2014-12-01

    Chemotherapy treatment recommendations traditionally have been based on the anatomic site of origin and the histology of the tumor. More recently, treatment options are transitioning to targeted therapies, in which drug selection is based on mutations present in an individual tumor. Genomic testing is a developing area that involves testing tumors to determine their molecular or genetic characteristics, then matching those characteristics to treatments that specifically target them.

  2. Strategies for microwave thermal treatment planning, navigation, and assessment

    NASA Astrophysics Data System (ADS)

    Ryan, Thomas P.

    2011-03-01

    Thermal treatment is commonly performed interstitially in either surgical or percutaneous procedures, using microwave antenna sources at 915 or 2540 MHz. There are a number of tools or aids as well as challenges for clinicians performing these procedures in the course of patient treatment. These challenges will be present whether the procedure is surgical, laparoscopic, or percutaneous, and include treatment planning, image guidance, navigation, coregistration in 3D, and treatment assessment. Treatment planning has been used historically in hyperthermia for microwave antenna arrays, but has yet to be properly applied in thermal ablation. Image assessment of thermal treatment is not typically performed in real time, although these tools will provide the clinician with further information to understand the extent of treatment and whether further treatment is needed. 3D imaging is available, but not coregistered to patient space. Navigation has been used in many medical specialties, but is also not in the clinician's toolbox in thermal treatment. Although treatment planning will lay out the skin entry and trajectory for each antenna placed, subsequently, each antenna needs to be tracked to accurately show placement in the patient and overlaid in patient space, along with the tumor target location. Some patient treatments may consist of multiple, but sequential single placements of an antenna, and guidance is even more critical to track positions and plan for the next insertion. Lastly, real-time image assessment will show the extent and shape of the coagulated lesion and which targets may have been undertreated. If used synchronously in arrays, MW power steering may also aid in filling in the ablation as the treatment progresses. This paper will analyze the present state-of-the art as well as a strategy to incorporate the various facets of planning, guidance, and assessment of treatment. The integration of thermal treatment planning, navigation and guidance, robotics

  3. Radiation Therapy in Keloids Treatment: History, Strategy, Effectiveness, and Complication.

    PubMed

    Xu, Jing; Yang, Elan; Yu, Nan-Ze; Long, Xiao

    2017-07-20

    Radiation therapy combined with surgical excision was considered as one of the most effective treatment plans for keloid lesions. However, there was no unanimity found over present literatures regarding the issue on optimized treatment strategy for keloids. We here provide a comprehensive review over this issue and emphasize on the influencing factors. The data analyzed in this review were searched from articles included in PubMed and EMBASE databases. The original articles and critical reviews discussing the application of radiation therapy in keloids treatment were selected for this review. The application of radiation therapy has transitioned from simple superficial X-ray irradiation to brachytherapy. Furthermore, several factors including radiation type, dose, fraction, interval, and complications were reviewed, and the results revealed that these factors were significant toward clinical outcome at various levels. Both past and present evidence support the idea that combination therapy of radiation and surgical therapy is safe and feasible. However, the optimization of treatment strategy was based on different radiation types and should take dose, fractions, interval, and complications into consideration, which will then decrease the rate of recurrence and increase the level of satisfaction.

  4. Radiation Therapy in Keloids Treatment: History, Strategy, Effectiveness, and Complication

    PubMed Central

    Xu, Jing; Yang, Elan; Yu, Nan-Ze; Long, Xiao

    2017-01-01

    Objective: Radiation therapy combined with surgical excision was considered as one of the most effective treatment plans for keloid lesions. However, there was no unanimity found over present literatures regarding the issue on optimized treatment strategy for keloids. We here provide a comprehensive review over this issue and emphasize on the influencing factors. Data Sources: The data analyzed in this review were searched from articles included in PubMed and EMBASE databases. Study Selection: The original articles and critical reviews discussing the application of radiation therapy in keloids treatment were selected for this review. Results: The application of radiation therapy has transitioned from simple superficial X-ray irradiation to brachytherapy. Furthermore, several factors including radiation type, dose, fraction, interval, and complications were reviewed, and the results revealed that these factors were significant toward clinical outcome at various levels. Conclusions: Both past and present evidence support the idea that combination therapy of radiation and surgical therapy is safe and feasible. However, the optimization of treatment strategy was based on different radiation types and should take dose, fractions, interval, and complications into consideration, which will then decrease the rate of recurrence and increase the level of satisfaction. PMID:28685723

  5. Water law as an adaptation strategy for global water scarcity in the future

    NASA Astrophysics Data System (ADS)

    Kakinuma, K.; Yoshikawa, S.; Endo, T.; Kanae, S.

    2014-12-01

    Water scarcity due to climate changes and growing human population is a major concern for the world. Adaptation and mitigation strategies should be developed for water scarcity in the future. Previous studies assessed the future water availability by hard technology (e.g., reservoirs, reclaimed and desalinated water plants) as adaptation strategies. On the other hand, soft path such as water law and policy would also be important for adaptation strategies. Water transfers is reallocation of water among water users. For example, distribution of the amount of available water is often heterogeneous especially during drought periods. If water transfers are permitted in these areas, water can be moved from surplus areas/sections to critical need areas/sections. There are several studies which describe the water transfer at the local scales (i.e., water bank in California), however the factors that determined the establishment of water transfer are not clear. If we can detect the factors, it could be used to estimate in which areas the water transfer would come into existence. This in turn would reduce the water stress. Here, we focus on historical interaction between human activity and water environments. Generally, rules of water use are developed by repeated discussion among water users. The frequency of these discussions would be related with their land use, frequency of drought and water resource sizes. For example, people in rice crop area need to discuss about water allocation compared to wheat crop area. Therefore, we examine the relationship between the permission of water transfer and factors such as water environment and human activity in the world.

  6. Antiangiogenic therapy for refractory colorectal cancer: current options and future strategies

    PubMed Central

    Riechelmann, Rachel; Grothey, Axel

    2016-01-01

    Even though significant improvements in the treatment of colorectal cancer (CRC) have been made in recent years, survival rates for metastatic colorectal cancer (mCRC) are poor. Effective treatment options for metastatic colorectal cancer remain limited, and new therapeutic strategies are desperately needed. Several tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) that target angiogenesis, a critical process for facilitating tumor cell growth, invasion, and metastasis, are either approved or in clinical development for the treatment of mCRC. Many of these agents have shown efficacy in mCRC, both as single agents and in combination with standard chemotherapy regimens. However, there is a need for predictive markers of response to identify those patients most likely to benefit from antiangiogenic therapy, and, to date, no markers of this type have been validated in patients. Additionally, because antiangiogenic agents typically cause cytostatic as opposed to cytotoxic antitumor effects, it is important to determine the best strategies for evaluating therapeutic response in mCRC to ensure maximum clinical benefit. In this review, we summarize the efficacy and tolerability of approved and investigational antiangiogenic agents for the treatment of mCRC. We also discuss potential markers of response to antiangiogenic agents and how these markers, along with appropriate endpoint selection, can improve clinical trial design. PMID:28203302

  7. Adapting to a Changing Colorado River: Making Future Water Deliveries More Reliable Through Robust Management Strategies

    NASA Astrophysics Data System (ADS)

    Groves, D.; Bloom, E.; Fischbach, J. R.; Knopman, D.

    2013-12-01

    The U.S. Bureau of Reclamation and water management agencies representing the seven Colorado River Basin States initiated the Colorado River Basin Study in January 2010 to evaluate the resiliency of the Colorado River system over the next 50 years and compare different options for ensuring successful management of the river's resources. RAND was asked to join this Basin Study Team in January 2012 to help develop an analytic approach to identify key vulnerabilities in managing the Colorado River basin over the coming decades and to evaluate different options that could reduce this vulnerability. Using a quantitative approach for planning under uncertainty called Robust Decision Making (RDM), the RAND team assisted the Basin Study by: identifying future vulnerable conditions that could lead to imbalances that could cause the basin to be unable to meet its water delivery objectives; developing a computer-based tool to define 'portfolios' of management options reflecting different strategies for reducing basin imbalances; evaluating these portfolios across thousands of future scenarios to determine how much they could improve basin outcomes; and analyzing the results from the system simulations to identify key tradeoffs among the portfolios. This talk will describe RAND's contribution to the Basin Study, focusing on the methodologies used to to identify vulnerabilities for Upper Basin and Lower Basin water supply reliability and to compare portfolios of options. Several key findings emerged from the study. Future Streamflow and Climate Conditions Are Key: - Vulnerable conditions arise in a majority of scenarios where streamflows are lower than historical averages and where drought conditions persist for eight years or more. - Depending where the shortages occur, problems will arise for delivery obligations for the upper river basin and the lower river basin. The lower river basin is vulnerable to a broader range of plausible future conditions. Additional Investments in

  8. Impacts of future air pollution mitigation strategies on the aerosol direct radiative forcing over Europe

    NASA Astrophysics Data System (ADS)

    Péré, J. C.; Colette, A.; Dubuisson, P.; Bessagnet, B.; Mallet, M.; Pont, V.

    2012-12-01

    Projections of aerosol emissions for 2030 have been recently generated and implemented in a comprehensive chemistry-transport model to analyse the future evolution of the aerosol radiative forcing over Europe. In this study, numerical developments based on an off-line coupling between the regional chemistry-transport model CHIMERE (extended by an aerosol optical module) and the radiative transfer code GAME have been implemented in order to simulate the interaction of physico-chemically resolved aerosols with radiation at regional scale. This novel approach is used to examine the shortwave aerosol direct radiative forcing response to two air pollution reduction scenarios for 2030 over Europe. Our study suggests that measures introduced to improve future air quality could have large implication on the aerosol climate forcing over Europe. Results of simulations indicate that abatement of aerosols in the near future could lead to a decrease of the aerosol cooling effect at the surface and at the top of the atmosphere over the main anthropogenic emission regions. Especially over the Moscow region, different strategies of reduction for scattering sulphate and absorbing black carbon aerosols between the two scenarios could result, however, in either a reduction or an enhancement in atmospheric radiative forcing.

  9. Present Status and Future Growth of Advanced Maintenance Technology and Strategy in US Manufacturing

    PubMed Central

    Jin, Xiaoning; Weiss, Brian A.; Siegel, David; Lee, Jay

    2016-01-01

    The goals of this paper are to 1) examine the current practices of diagnostics, prognostics, and maintenance employed by United States (U.S.) manufacturers to achieve productivity and quality targets and 2) to understand the present level of maintenance technologies and strategies that are being incorporated into these practices. A study is performed to contrast the impact of various industry-specific factors on the effectiveness and profitability of the implementation of prognostics and health management technologies, and maintenance strategies using both surveys and case studies on a sample of U.S. manufacturing firms ranging from small to mid-sized enterprises (SMEs) to large-sized manufacturing enterprises in various industries. The results obtained provide important insights on the different impacts of specific factors on the successful adoption of these technologies between SMEs and large manufacturing enterprises. The varying degrees of success with respect to current maintenance programs highlight the opportunity for larger manufacturers to improve maintenance practices and consider the use of advanced prognostics and health management (PHM) technology. This paper also provides the existing gaps, barriers, future trends, and roadmaps for manufacturing PHM technology and maintenance strategy. PMID:28058173

  10. Present Status and Future Growth of Advanced Maintenance Technology and Strategy in US Manufacturing.

    PubMed

    Jin, Xiaoning; Weiss, Brian A; Siegel, David; Lee, Jay

    2016-01-01

    The goals of this paper are to 1) examine the current practices of diagnostics, prognostics, and maintenance employed by United States (U.S.) manufacturers to achieve productivity and quality targets and 2) to understand the present level of maintenance technologies and strategies that are being incorporated into these practices. A study is performed to contrast the impact of various industry-specific factors on the effectiveness and profitability of the implementation of prognostics and health management technologies, and maintenance strategies using both surveys and case studies on a sample of U.S. manufacturing firms ranging from small to mid-sized enterprises (SMEs) to large-sized manufacturing enterprises in various industries. The results obtained provide important insights on the different impacts of specific factors on the successful adoption of these technologies between SMEs and large manufacturing enterprises. The varying degrees of success with respect to current maintenance programs highlight the opportunity for larger manufacturers to improve maintenance practices and consider the use of advanced prognostics and health management (PHM) technology. This paper also provides the existing gaps, barriers, future trends, and roadmaps for manufacturing PHM technology and maintenance strategy.

  11. Vulnerability of maize production under future climate change: possible adaptation strategies.

    PubMed

    Bannayan, Mohammad; Paymard, Parisa; Ashraf, Batool

    2016-10-01

    Climate change can affect the productivity and geographic distribution of crops. Therefore, evaluation of adaptive management options is crucial in dealing with negative impacts of climate change. The objectives of this study were to simulate the impacts of climate change on maize production in the north-east of Iran. Moreover, vulnerability index which indicated that how much of the crop yield loss is related to the drought was computed for each location to identify where adaptation and mitigation strategies are effective. Different sowing dates were also applied as an adaptation approach to decrease the negative impacts of climate change in study area. The results showed that the maize yield would decline during the 21st century from -2.6% to -82% at all study locations in comparison with the baseline. The result of vulnerability index also indicated that using the adaptation strategies could be effective in all of the study areas. Using different sowing dates as an adaptation approach showed that delaying the sowing date will be advantageous in order to obtain higher yield in all study locations in future. This study provided insight regarding the climate change impacts on maize production and the efficacy of adaptation strategies. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  12. Future: new strategies for hospitalists to overcome challenges in teaching on today's wards.

    PubMed

    Martin, Shannon K; Farnan, Jeanne M; Arora, Vineet M

    2013-07-01

    Changes in the clinical learning environment under resident duty hours restrictions have introduced a number of challenges on today's wards. Additionally, the current group of medical trainees is largely represented by the Millennial Generation, a generation characterized by an affinity for technology, interaction, and group-based learning. Special attention must be paid to take into account the learning needs of a generation that has only ever known life with duty hours. A mnemonic for strategies to augment teaching rounds for hospitalists was created using an approach that considers time limitations due to duty hours as well as the preferences of Millennial learners. These strategies to enhance learning during teaching rounds are Flipping the Wards, Using Documentation to Teach, Technology-Enabled Teaching, Using Guerilla Teaching Tactics, Rainy Day Teaching, and Embedding Teaching Moments into Rounds (FUTURE). Hospitalists serving as teaching attendings should consider these possible strategies as ways to enhance teaching in the post-duty hours era. These techniques appeal to the preferences of today's learners in an environment often limited by time constraints. Hospitalists are well positioned to champion innovative approaches to teaching in a dynamic and evolving clinical learning environment. © 2013 Society of Hospital Medicine.

  13. [Treatment strategy of insomnia for the patients with metabolic syndrome].

    PubMed

    Takaesu, Yoshikazu; Inoue, Yuichi

    2012-07-01

    Insomnia has been reported to underlie the development and aggravation of metabolic syndrome including hypertension, cardiovascular disease, and diabetes. Treatment of insomnia is important for both the management and prevention of these comorbid disorders. We introduced the treatment strategy of insomnia for the patients with metabolic syndrome. For the better management of insomnia, sleep hygiene education should be given first, and adequate drug therapy should be started thereafter. Cognitive behavioral therapy is useful not only for insomnia symptom but also for the reducing amount of drug and prevention of the recurrence of insomnia. We expect that progress in the management of insomnia would result in the better treatment outcome of metabolic syndrome in general practice.

  14. Present and future drug treatment for Parkinson's disease

    PubMed Central

    Schapira, A

    2005-01-01

    Considerable advances made in defining the aetiology, pathogenesis, and pathology of Parkinson's disease (PD) have resulted in the development and rapid expansion of the pharmacopoeia available for treatment. Anticholinergics were used before the introduction of levodopa which is now the drug most commonly used. Dopamine agonists are effective when used alone or as an adjunct to levodopa, while monoamine oxidase B inhibitors improve motor function in early and advanced PD. However, treatment mainly addresses the dopaminergic features of the disease and leaves its progressive course unaffected; the drug treatment available for the management of non-motor symptoms is limited. This article seeks to set current treatment options in context, review emerging and novel drug treatments for PD, and assess the prospects for disease modification. Surgical therapies are not considered. PMID:16227533

  15. Innovative strategies for closing the mental health treatment gap globally.

    PubMed

    Rebello, Tahilia J; Marques, Andrea; Gureje, Oye; Pike, Kathleen M

    2014-07-01

    In the field of global mental health, an enormous gap between what we know and what we do exists in the delivery of clinical care. Creative and effective strategies that surmount the barriers to provision of mental healthcare are essential to improve the lives of millions affected by mental illness. This article provides a review of three classes of innovative strategies currently being developed and implemented to diminish the mental health treatment gap globally. This review provides recent evidence related to the feasibility of implementation and efficacy for the following three classes of innovation that show promise for building clinical capacity and expanding mental health coverage: integration of mental health services into primary care; expansion of human capacity through task sharing and training of nonspecialists; and innovative use of technological platforms to enhance access, cut costs, and reduce stigma. The strategies outlined in this review hold great potential for enhancing mental health treatment services, and address some of the major barriers globally to accessing mental healthcare, such as scarcity of resources (infrastructure, capacity, and funding) and stigma. Despite much evidence supporting the efficacy of these models, thorough studies that test their feasibility, acceptability, utility, and effectiveness in various contexts, including low-income and middle-income countries, are required. Moreover, these innovations require social support and political will in order to be successfully implemented and scaled-up such that they have a meaningful impact on the burden of disease associated with mental illness worldwide.

  16. Evidence-based Management Strategies for Treatment of Chronic Wounds

    PubMed Central

    Werdin, Frank; Tennenhaus, Mayer; Schaller, Hans-Eberhardt; Rennekampff, Hans-Oliver

    2009-01-01

    The care and management of patients with chronic wounds and their far-reaching effects challenge both the patient and the practitioner. Further complicating this situation is the paucity of evidence-based treatment strategies for chronic wound care. After searching both MEDLINE and Cochrane databases, we reviewed currently available articles concerning chronic wound care. Utilizing this information, we have outlined a review of current, evidence-based concepts as they pertain to the treatment of chronic wounds, focusing on fundamental treatment principles for the management of venous, arterial, diabetic, and pressure ulcers. Individualized treatment options as well as general wound management principles applicable to all varieties of chronic wounds are described. Classification and treatment guidelines as well as the adoption of the TIME acronym facilitate an organized conceptional approach to wound care. In so doing, individual aspects of generalized wound care such as debridement, infection, and moisture control as well as attention to the qualities of the wound edge are comprehensively evaluated, communicated, and addressed. Effective adjuvant agents for the therapy of chronic wounds including nutritional and social support measures are listed, as is a brief review of strategies helpful for preventing recurrence. An appreciation of evidence-based treatment pathways and an understanding of the pathophysiology of chronic wounds are important elements in the management of patients with chronic wounds. To achieve effective and long-lasting results, a multidisciplinary approach to patient care, focused on the education and coordination of patient, family as well as medical and support staff can prove invaluable. PMID:19578487

  17. Blood pressure control in hypertension. Pros and cons of available treatment strategies.

    PubMed

    Mancia, Giuseppe; Rea, Federico; Cuspidi, Cesare; Grassi, Guido; Corrao, Giovanni

    2017-02-01

    The low rate of blood pressure (BP) control that characterizes the hypertensive population in real life is traditionally associated to factors such as low adherence of patients to the prescribed treatment regimen, physicians' therapeutic inertia, and deficiencies of the healthcare systems. This study will focus on a fourth factor that may also be importantly involved, i.e. reluctance to adopt drug treatment strategies that more effectively reduce an elevated BP. The point will be made that, vis-à-vis strategies based on patients' persistence in monotherapy, drug combinations are accompanied by a much more frequent BP control. In particular, it will be argued that compared with the administration of additional drugs after initial monotherapy, use of combination treatment from the beginning may carry important advantages, such as a faster BP control, and thus an earlier protection in patients at a high cardiovascular risk and a better adherence to the prescribed drugs and thus a more frequent long-term achievement of target BP values, possibly also with a more effective cardiovascular protection. This may justify a more clear support of this treatment strategy by future guidelines, in the attempt to lessen the contribution of hypertension to cardiovascular disease and death.

  18. Modeling test and treatment strategies for presymptomatic Alzheimer disease.

    PubMed

    Burke, James F; Langa, Kenneth M; Hayward, Rodney A; Albin, Roger L

    2014-01-01

    In this study, we developed a model of presymptomatic treatment of Alzheimer disease (AD) after a screening diagnostic evaluation and explored the circumstances required for an AD prevention treatment to produce aggregate net population benefit. Monte Carlo simulation methods were used to estimate outcomes in a simulated population derived from data on AD incidence and mortality. A wide variety of treatment parameters were explored. Net population benefit was estimated in aggregated QALYs. Sensitivity analyses were performed by individually varying the primary parameters. In the base-case scenario, treatment effects were uniformly positive, and net benefits increased with increasing age at screening. A highly efficacious treatment (i.e. relative risk 0.6) modeled in the base-case is estimated to save 20 QALYs per 1000 patients screened and 221 QALYs per 1000 patients treated. Highly efficacious presymptomatic screen and treat strategies for AD are likely to produce substantial aggregate population benefits that are likely greater than the benefits of aspirin in primary prevention of moderate risk cardiovascular disease (28 QALYS per 1000 patients treated), even in the context of an imperfect treatment delivery environment.

  19. Modeling Test and Treatment Strategies for Presymptomatic Alzheimer Disease

    PubMed Central

    Burke, James F.; Langa, Kenneth M.; Hayward, Rodney A.; Albin, Roger L.

    2014-01-01

    Objectives In this study, we developed a model of presymptomatic treatment of Alzheimer disease (AD) after a screening diagnostic evaluation and explored the circumstances required for an AD prevention treatment to produce aggregate net population benefit. Methods Monte Carlo simulation methods were used to estimate outcomes in a simulated population derived from data on AD incidence and mortality. A wide variety of treatment parameters were explored. Net population benefit was estimated in aggregated QALYs. Sensitivity analyses were performed by individually varying the primary parameters. Findings In the base-case scenario, treatment effects were uniformly positive, and net benefits increased with increasing age at screening. A highly efficacious treatment (i.e. relative risk 0.6) modeled in the base-case is estimated to save 20 QALYs per 1000 patients screened and 221 QALYs per 1000 patients treated. Conclusions Highly efficacious presymptomatic screen and treat strategies for AD are likely to produce substantial aggregate population benefits that are likely greater than the benefits of aspirin in primary prevention of moderate risk cardiovascular disease (28 QALYS per 1000 patients treated), even in the context of an imperfect treatment delivery environment. PMID:25474698

  20. Future scientific drilling in the Arctic Ocean: Key objectives, areas, and strategies

    NASA Astrophysics Data System (ADS)

    Stein, R.; Coakley, B.; Mikkelsen, N.; O'Regan, M.; Ruppel, C.

    2012-04-01

    Past, Present and Future Changes in Arctic Terrestrial and Marine Systems" (Kananaskis, Alberta/Canada, February 2012). During these workshops, key areas and key scientific themes as well as drilling and site-survey strategies were discussed. Major scientific themes for future Arctic drilling will include: - The Arctic Ocean during the transition from greenhouse to icehouse conditions and millennial scale climate changes; - Physical and chemical changes of the evolving Polar Ocean and Arctic gateways; - Impact of Pleistocene/Holocene warming and sea-level rise on upper continental slope and shelf gas hydrates and on shelf permafrost; - Land-ocean interactions; - Tectonic evolution and birth of the Arctic Ocean basin: Arctic ridges, sea floor spreading and global lithosphere processes. When thinking about future Arctic drilling, it should be clearly emphasized that for the precise planning of future Arctic Ocean drilling campaigns, including site selection, evaluation of proposed drill sites for safety and environmental protection, etc., comprehensive site survey data are needed first. This means that the development of a detailed site survey strategy is a major challenge for the coming years. Here, an overview of perspectives and plans for future Arctic Ocean drilling will be presented.

  1. Mucopolysaccharidosis type III (Sanfilippo Syndrome): emerging treatment strategies.

    PubMed

    de Ruijter, J; Valstar, M J; Wijburg, F A

    2011-06-01

    Mucopolysaccharosis III (MPS III) is a lysosomal storage disorder and belongs to the group of mucopolysaccharidoses. MPS III is caused by a deficiency of one of the four enzymes catalyzing the degradation of the glycosaminoglycan heparan sulfate. MPS III is clinically characterized by progressive dementia with distinct behavioral disturbances and relatively mild somatic disease. This review will summarize and discuss the available and potential future therapeutic options for patients with MPS III. This includes enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), substrate reduction therapy (SRT), chaperone-mediated therapy, and gene therapy. Although clinical efficacy has not yet been fully demonstrated for any of these therapies, it is likely that future developments will lead to disease-modifying treatment for this devastating disease.

  2. Heart failure therapies: new strategies for old treatments and new treatments for old strategies.

    PubMed

    Halushka, Marc K; Mitchell, Richard N; Padera, Robert F

    Heart failure, whether acute or chronic, remains a major health care crisis affecting almost 6 million Americans and over 23 million people worldwide. Roughly half of those affected will die within 5 years, and the annual cost exceeds $30 billion in the US alone. Although medical therapy has made some modest inroads in partially stemming the heart failure tsunami, there remains a significant population for whom medication is unsuccessful or has ceased being effective; such patients can benefit from heart transplantation or mechanical circulatory support. Indeed, in the past quarter century (and as covered in Cardiovascular Pathology over those years), significant improvements in pathologic understanding and in engineering design have materially enhanced the toolkit of options for such refractory patients. Mechanical devices, whether total artificial hearts or ventricular assist devices, have been reengineered to reduce complications and basic wear and tear. Transplant survival has also been extended through a better comprehension of and improved therapies for transplant vasculopathy and antibody-mediated rejection. Here we review the ideas and treatments from the last 25 years and highlight some of the new directions in nonpharmacologic heart failure therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Dietary Strategies for the Treatment of Cadmium and Lead Toxicity

    PubMed Central

    Zhai, Qixiao; Narbad, Arjan; Chen, Wei

    2014-01-01

    Cadmium (Cd) and lead (Pb) are toxic heavy metals that cause adverse health effects in humans and animals. Chelation therapy, the conventional treatment for heavy metal toxicity, is reported to have a number of safety and efficacy issues. Recent studies have shown that dietary supplements play important roles in protecting against Cd and Pb toxicity. This paper reviews the evidence for protective effects of essential metals, vitamins, edible plants, phytochemicals, probiotics and other dietary supplements against Cd and Pb toxicity and describes the proposed possible mechanisms. Based on these findings, dietary strategies are recommended for people at risk of Cd and Pb exposure. The application of these strategies is advantageous for both the prevention and alleviation of Cd and Pb toxicity, as such supplements can be added easily and affordably to the daily diet and are expected to have very few side effects compared to the chelation therapy. PMID:25594439

  4. Novel treatment strategies for brain tumors and metastases

    PubMed Central

    El-Habashy, Salma E.; Nazief, Alaa M.; Adkins, Chris E.; Wen, Ming Ming; El-Kamel, Amal H.; Hamdan, Ahmed M.; Hanafy, Amira S.; Terrell, Tori O.; Mohammad, Afroz S.; Lockman, Paul R.; Nounou, Mohamed Ismail

    2015-01-01

    This review summarizes patent applications in the past 5 years for the management of brain tumors and metastases. Most of the recent patents discuss one of the following strategies: the development of new drug entities that specifically target the brain cells, the blood–brain barrier and the tumor cells, tailor-designing a novel carrier system that is able to perform multitasks and multifunction as a drug carrier, targeting vehicle and even as a diagnostic tool, direct conjugation of a US FDA approved drug with a targeting moiety, diagnostic moiety or PK modifying moiety, or the use of innovative nontraditional approaches such as genetic engineering, stem cells and vaccinations. Until now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are actively ongoing to take brain tumor targeting, and novel and targeted CNS delivery systems to potential clinical application. PMID:24998288

  5. Dietary strategies for the treatment of cadmium and lead toxicity.

    PubMed

    Zhai, Qixiao; Narbad, Arjan; Chen, Wei

    2015-01-14

    Cadmium (Cd) and lead (Pb) are toxic heavy metals that cause adverse health effects in humans and animals. Chelation therapy, the conventional treatment for heavy metal toxicity, is reported to have a number of safety and efficacy issues. Recent studies have shown that dietary supplements play important roles in protecting against Cd and Pb toxicity. This paper reviews the evidence for protective effects of essential metals, vitamins, edible plants, phytochemicals, probiotics and other dietary supplements against Cd and Pb toxicity and describes the proposed possible mechanisms. Based on these findings, dietary strategies are recommended for people at risk of Cd and Pb exposure. The application of these strategies is advantageous for both the prevention and alleviation of Cd and Pb toxicity, as such supplements can be added easily and affordably to the daily diet and are expected to have very few side effects compared to the chelation therapy.

  6. Novel treatment strategies for brain tumors and metastases.

    PubMed

    El-Habashy, Salma E; Nazief, Alaa M; Adkins, Chris E; Wen, Ming Ming; El-Kamel, Amal H; Hamdan, Ahmed M; Hanafy, Amira S; Terrell, Tori O; Mohammad, Afroz S; Lockman, Paul R; Nounou, Mohamed Ismail

    2014-05-01

    This review summarizes patent applications in the past 5 years for the management of brain tumors and metastases. Most of the recent patents discuss one of the following strategies: the development of new drug entities that specifically target the brain cells, the blood-brain barrier and the tumor cells, tailor-designing a novel carrier system that is able to perform multitasks and multifunction as a drug carrier, targeting vehicle and even as a diagnostic tool, direct conjugation of a US FDA approved drug with a targeting moiety, diagnostic moiety or PK modifying moiety, or the use of innovative nontraditional approaches such as genetic engineering, stem cells and vaccinations. Until now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are actively ongoing to take brain tumor targeting, and novel and targeted CNS delivery systems to potential clinical application.

  7. Visceral leishmaniasis: Revisiting current treatments and approaches for future discoveries.

    PubMed

    No, Joo Hwan

    2016-03-01

    The current treatments for visceral leishmaniasis are old and toxic with limited routes of administration. The emergence of drug-resistant Leishmania threatens the efficacy of the existing reservoir of antileishmanials, leading to an urgent need to develop new treatments. It is particularly important to review and understand how the current treatments act against Leishmania in order to identify valid drug targets or essential pathways for next-generation antileishmanials. It is equally important to adapt newly emerging biotechnologies to facilitate the current research on the development of novel antileishmanials in an efficient fashion. This review covers the basic background of the current visceral leishmaniasis treatments with an emphasis on the modes of action. It briefly discusses the role of the immune system in aiding the chemotherapy of leishmaniasis, describes potential new antileishmanial drug targets and pathways, and introduces recent progress on the utilization of high-throughput phenotypic screening assays to identify novel antileishmanial compounds.

  8. Nuclear Energy - Hydrogen Production - Fuel Cell: A Road Towards Future China's Sustainable Energy Strategy

    SciTech Connect

    Zhiwei Zhou

    2006-07-01

    Sustainable development of Chinese economy in 21. century will mainly rely on self-supply of clean energy with indigenous natural resources. The burden of current coal-dominant energy mix and the environmental stress due to energy consumptions has led nuclear power to be an indispensable choice for further expanding electricity generation capacity in China and for reducing greenhouse effect gases emission. The application of nuclear energy in producing substitutive fuels for road transportation vehicles will also be of importance in future China's sustainable energy strategy. This paper illustrates the current status of China's energy supply and the energy demand required for establishing a harmonic and prosperous society in China. In fact China's energy market faces following three major challenges, namely (1) gaps between energy supply and demand; (2) low efficiency in energy utilization, and (3) severe environmental pollution. This study emphasizes that China should implement sustainable energy development policy and pay great attention to the construction of energy saving recycle economy. Based on current forecast, the nuclear energy development in China will encounter a high-speed track. The demand for crude oil will reach 400-450 million tons in 2020 in which Chinese indigenous production will remain 180 million tons. The increase of the expected crude oil will be about 150 million tons on the basis of 117 million tons of imported oil in 2004 with the time span of 15 years. This demand increase of crude oil certainly will influence China's energy supply security and to find the substitution will be a big challenge to Chinese energy industry. This study illustrates an analysis of the market demands to future hydrogen economy of China. Based on current status of technology development of HTGR in China, this study describes a road of hydrogen production with nuclear energy. The possible technology choices in relation to a number of types of nuclear reactors are

  9. [Future prospects for hepatitis C treatment: without interferon and ribavirin?].

    PubMed

    Lens, Sabela; Alfaro, Ignacio

    2014-05-01

    The hepatitis C virus is an important health problem worldwide. Currently, the standard treatment of genotype 1 chronic hepatitis C is the combination of pegylated interferon, ribavirin and a first-generation protease inhibitor: telaprevir or boceprevir. This triple therapy has improved the efficacy of treatment but has also increased regimen complexity, costs, and the number of adverse effects (mainly hematological and cutaneous). Unfortunately, viral response rates are still suboptimal in patients with cirrhosis, particularly those with a prior null response. Moreover, studies carried out in clinical practice have shown that the presence of advanced fibrosis confers a high risk of developing severe adverse effects during treatment (infection, decompensation and even death). It is therefore essential to select candidates for triple therapy according to their risk of complications and possibilities for cure. In this scenario, interferon (and ribavirin)-free combinations are very safe and well tolerated first-line treatments. This review describes the current treatment of hepatitis C as well as the latest results of studies combining distinct direct antiviral agents without interferon. It is hoped that these drugs will be available shortly, although their cost may be high. Consequently, it is essential to identify those patients who could derive the greatest benefit from these treatments. Copyright © 2014 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

  10. Treatment of Helicobacter pylori infection: Current and future insights

    PubMed Central

    Safavi, Maliheh; Sabourian, Reyhaneh; Foroumadi, Alireza

    2016-01-01

    Helicobacter pylori (H. pylori) is an important major cause of peptic ulcer disease and gastric malignancies such as mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma worldwide. H. pylori treatment still remains a challenge, since many determinants for successful therapy are involved such as individual primary or secondary antibiotics resistance, mucosal drug concentration, patient compliance, side-effect profile and cost. While no new drug has been developed, current therapy still relies on different mixture of known antibiotics and anti-secretory agents. A standard triple therapy consisting of two antibiotics and a proton-pump inhibitor proposed as the first-line regimen. Bismuth-containing quadruple treatment, sequential treatment or a non-bismuth quadruple treatment (concomitant) are also an alternative therapy. Levofloxacin containing triple treatment are recommended as rescue treatment for infection of H. pylori after defeat of first-line therapy. The rapid acquisition of antibiotic resistance reduces the effectiveness of any regimens involving these remedies. Therefore, adding probiotic to the medications, developing anti-H. pylori photodynamic or phytomedicine therapy, and achieving a successful H. pylori vaccine may have the promising to present synergistic or additive consequence against H. pylori, because each of them exert different effects. PMID:26798626

  11. Treatment of Cannabis Use Disorder: Current Science and Future Outlook

    PubMed Central

    Sherman, Brian J.; McRae-Clark, Aimee L.

    2016-01-01

    Cannabis is the most commonly used illicit substance in the United States. Rates of cannabis use and cannabis use disorder have increased in the past decade, paralleling changes in the legal and political climate favoring legalization. Almost 20 million people aged 12 years or older report past-month cannabis use, and 8 million report daily or near-daily use. Concurrently, the perception that cannabis use poses a significant risk of negative consequences has decreased. Contrary to this perception, heavy cannabis use is associated with cognitive impairment, increased risk for psychotic disorders and other mental health problems, lower education attainment, and unemployment. Clinical trials of various treatments for cannabis use disorder have likewise increased, focusing primarily on psychotherapy treatments, specifically, motivational enhancement therapy, cognitive behavioral therapy, and contingency management. Their findings suggest that a combination of these three modalities produces the best abstinence outcomes, although abstinence rates remain modest and decline after treatment. More recently, pharmacotherapy trials have been conducted as adjunctive interventions to psychosocial treatment. N-acetylcysteine and gabapentin are two of the most promising medications, although no pharmacologic treatment has emerged as clearly efficacious. In this review, we provide a detailed summary of clinical trials that evaluated psychotherapy and pharmacotherapy for treating cannabis use disorder and discuss emerging areas of clinical research and cannabis-specific barriers to treatment. PMID:27027272

  12. Treatment of Cannabis Use Disorder: Current Science and Future Outlook.

    PubMed

    Sherman, Brian J; McRae-Clark, Aimee L

    2016-05-01

    Cannabis is the most commonly used illicit substance in the United States. Rates of cannabis use and cannabis use disorder (CUD) have increased in the past decade, paralleling changes in the legal and political climate favoring legalization. Almost 20 million people 12 years or older report past-month cannabis use, and 8 million report daily or near-daily use. Concurrently, the perception that cannabis use poses a significant risk of negative consequences has decreased. Contrary to this perception, heavy cannabis use is associated with cognitive impairment, increased risk for psychotic disorders and other mental health problems, lower education attainment, and unemployment. Clinical trials of various treatments for CUD have likewise increased, focusing primarily on psychotherapy treatments, specifically motivational enhancement therapy, cognitive behavioral therapy, and contingency management. Their findings suggest that a combination of these three modalities produces the best abstinence outcomes, although abstinence rates remain modest and decline after treatment. More recently, pharmacotherapy trials have been conducted as adjunctive interventions to psychosocial treatment. N-acetylcysteine and gabapentin are two of the most promising medications, although no pharmacologic treatment has emerged as clearly efficacious. In this review, we provide a detailed summary of clinical trials that evaluated psychotherapy and pharmacotherapy for treating CUD and discuss emerging areas of clinical research and cannabis-specific barriers to treatment.

  13. Regional Treatment Strategies for In-transit Melanoma Metastasis

    PubMed Central

    Raymond, Amanda K.; Tyler, Douglas S.

    2010-01-01

    Synopsis For in-transit melanoma confined to the extremities, regional chemotherapy in the form of hyperthermic isolated limb perfusion and isolated limb infusion are effective treatment modalities carrying superior response rates to current standard systemic therapy. Despite high response rates, most patients will eventually recur, supporting the role for novel research aimed at improving durable responses and minimizing toxicity. Although the standard cytotoxic agent for regional chemotherapy is melphalan, alternative agents such as temozolomide are currently being tested with promising preliminary results. Current strategies for improving chemosensitivity to regional chemotherapy are aimed at overcoming classic resistance mechanisms such as drug metabolism and DNA repair, increasing drug delivery, inhibiting tumor-specific angiogenesis, and decreasing the apoptotic threshold of melanoma cells. Concurrent with development and testing of these agents, genomic profiling and biomolecular analysis of acquired tumor tissue may define patterns of tumor resistance and sensitivity from which personalized treatment may be tailored to optimize efficacy. Here, rational strategies for treatment of in-transit melanoma are outlined with special emphasis on current translational and clinical research efforts. PMID:21111960

  14. Optimal Treatment Strategy for a Tumor Model under Immune Suppression

    PubMed Central

    Kim, Kwang Su; Cho, Giphil; Jung, Il Hyo

    2014-01-01

    We propose a mathematical model describing tumor-immune interactions under immune suppression. These days evidences indicate that the immune suppression related to cancer contributes to its progression. The mathematical model for tumor-immune interactions would provide a new methodology for more sophisticated treatment options of cancer. To do this we have developed a system of 11 ordinary differential equations including the movement, interaction, and activation of NK cells, CD8+T-cells, CD4+T cells, regulatory T cells, and dendritic cells under the presence of tumor and cytokines and the immune interactions. In addition, we apply two control therapies, immunotherapy and chemotherapy to the model in order to control growth of tumor. Using optimal control theory and numerical simulations, we obtain appropriate treatment strategies according to the ratio of the cost for two therapies, which suggest an optimal timing of each administration for the two types of models, without and with immunosuppressive effects. These results mean that the immune suppression can have an influence on treatment strategies for cancer. PMID:25140193

  15. Biofilm infections, their resilience to therapy and innovative treatment strategies.

    PubMed

    Römling, U; Balsalobre, C

    2012-12-01

    Biofilm formation of microorganisms causes persistent tissue and foreign body infections resistant to treatment with antimicrobial agents. Up to 80% of human bacterial infections are biofilm associated; such infections are most frequently caused by Staphylococcus epidermidis, Pseudomonas aeruginosa, Staphylococcus aureus and Enterobacteria such as Escherichia coli. The accurate diagnosis of biofilm infections is often difficult, which prevents the appropriate choice of treatment. As biofilm infections significantly contribute to patient morbidity and substantial healthcare costs, novel strategies to treat these infections are urgently required. Nucleotide second messengers, c-di-GMP, (p)ppGpp and potentially c-di-AMP, are major regulators of biofilm formation and associated antibiotic tolerance. Consequently, different components of these signalling networks might be appropriate targets for antibiofilm therapy in combination with antibiotic treatment strategies. In addition, cyclic di-nucleotides are microbial-associated molecular patterns with an almost universal presence. Their conserved structures sensed by the eukaryotic host have a widespread effect on the immune system. Thus, cyclic di-nucleotides are also potential immunotherapeutic agents to treat antibiotic-resistant bacterial infections.

  16. Biological Treatment Approaches for Degenerative Disc Disease: A Review of Clinical Trials and Future Directions

    PubMed Central

    Moriguchi, Yu; Hussain, Ibrahim; Bonssar, Lawrence; Härtl, Roger

    2016-01-01

    Biologic-based treatment strategies for musculoskeletal diseases have gained traction over the past 20 years as alternatives to invasive, costly, and complicated surgical interventions. Spinal degenerative disc disease (DDD) is among the anatomic areas being investigated among this group, notably due to its high incidence and functional debilitation. In this review, we report the literature encompassing the use of biologic-based therapies for DDD. Articles published between January 1995 and November 2015 were reviewed, with a subset meeting the primary and secondary inclusion criteria of clinical trial results that could be sub-classified into bimolecular, cell-based, or gene therapies, as well as studies investigating the utility of allogeneic and tissue-engineered intervertebral discs. Ongoing clinical trials that have not yet published results are also mentioned to present the current state of the field. This exciting area has demonstrated positive and encouraging results across multiple strategies; thus, future bimolecular and regenerative techniques and understanding will likely lead to an increase in the number of human clinical trials assessing these therapies. PMID:28018762

  17. Optimising treatment for COPD--new strategies for combination therapy.

    PubMed

    Welte, T

    2009-08-01

    Chronic obstructive pulmonary disease (COPD) is a multi-component disease characterised by airflow limitation and airway inflammation. Exacerbations of COPD have a considerable impact on the quality of life, daily activities and general well-being of patients and are a great burden on the health system. Thus, the aims of COPD management include not only relieving symptoms and preventing disease progression but also preventing and treating exacerbations. Attention towards the day-to-day burden of the disease is also required in light of evidence that suggests COPD may be variable throughout the day with morning being the time when symptoms are most severe and patients' ability to perform regular morning activities the most problematic. While available therapies improve clinical symptoms and decrease airway inflammation, they do not unequivocally slow long-term progression or address all disease components. With the burden of COPD continuing to increase, research into new and improved treatment strategies to optimise pharmacotherapy is ongoing - in particular, combination therapies, with a view to their complementary modes of action enabling multiple components of the disease to be addressed. Evidence from recent clinical trials indicates that triple therapy, combining an anticholinergic with an inhaled corticosteroid and a long-acting beta(2)-agonist, may provide clinical benefits additional to those associated with each treatment alone in patients with more severe COPD. This article reviews the evidence for treatment strategies used in COPD with a focus on combination therapies and introduces the 3-month CLIMB study (Evaluation of Efficacy and Safety of Symbicort as an Add-on Treatment to Spiriva in Patients With Severe COPD) which investigated the potential treatment benefits of combining tiotropium with budesonide/formoterol in patients with COPD with regard to lung function, exacerbations, symptoms and morning activities.

  18. Treatment Strategies for Human Arboviral Infections Applicable to Veterinary Medicine

    DTIC Science & Technology

    1992-06-16

    0 Lf Reprintod from Tropical Veterinary Medicine : Current Issues and Perspectives 1• • Volume 653 of the Annals of the New York Academy of Sciences...June 16, 1992 _ Treatment Strategies for Human = __ Arboviral Infections Applicable to I= ’ Veterinary Medicine = ! Chlh. MEIR KENDE (A) U •Department...A 3 0. C . U. 2 * >. U u U>1 it 020 ce*. 0. , -,r- 8 C- ed U a - .; U~u0.M KENDE: HUMAN ARBOVIRAL INFECTIONS AND VETERINARY MEDICINE 299 TABLE 2

  19. Energy Efficiency Strategies for Municipal Wastewater Treatment Facilities

    SciTech Connect

    Daw, J.; Hallett, K.; DeWolfe, J.; Venner, I.

    2012-01-01

    Water and wastewater systems are significant energy consumers with an estimated 3%-4% of total U.S. electricity consumption used for the movement and treatment of water and wastewater. Water-energy issues are of growing importance in the context of water shortages, higher energy and material costs, and a changing climate. In this economic environment, it is in the best interest for utilities to find efficiencies, both in water and energy use. Performing energy audits at water and wastewater treatment facilities is one way community energy managers can identify opportunities to save money, energy, and water. In this paper the importance of energy use in wastewater facilities is illustrated by a case study of a process energy audit performed for Crested Butte, Colorado's wastewater treatment plant. The energy audit identified opportunities for significant energy savings by looking at power intensive unit processes such as influent pumping, aeration, ultraviolet disinfection, and solids handling. This case study presents best practices that can be readily adopted by facility managers in their pursuit of energy and financial savings in water and wastewater treatment. This paper is intended to improve community energy managers understanding of the role that the water and wastewater sector plays in a community's total energy consumption. The energy efficiency strategies described provide information on energy savings opportunities, which can be used as a basis for discussing energy management goals with water and wastewater treatment facility managers.

  20. Ecological models supporting environmental decision making: a strategy for the future

    USGS Publications Warehouse

    Schmolke, Amelie; Thorbek, Pernille; DeAngelis, Donald L.; Grimm, Volker

    2010-01-01

    Ecological models are important for environmental decision support because they allow the consequences of alternative policies and management scenarios to be explored. However, current modeling practice is unsatisfactory. A literature review shows that the elements of good modeling practice have long been identified but are widely ignored. The reasons for this might include lack of involvement of decision makers, lack of incentives for modelers to follow good practice, and the use of inconsistent terminologies. As a strategy for the future, we propose a standard format for documenting models and their analyses: transparent and comprehensive ecological modeling (TRACE) documentation. This standard format will disclose all parts of the modeling process to scrutiny and make modeling itself more efficient and coherent.

  1. Alloy Design Strategies and Future Trends in High-Entropy Alloys

    NASA Astrophysics Data System (ADS)

    Yeh, Jien-Wei

    2013-12-01

    High-entropy alloys (HEAs) are newly emerging advanced materials. In contrast to conventional alloys, HEAs contain multiple principal elements, often five or more in equimolar or near-equimolar ratios. The basic principle behind HEAs is that solid-solution phases are relatively stabilized by their significantly high entropy of mixing compared to intermetallic compounds, especially at high temperatures. This makes them feasibly synthesized, processed, analyzed, and manipulated, and as well provides many opportunities for us. There are huge numbers of possible compositions and combinations of properties in the HEA field. Wise alloy design strategies for suitable compositions and processes to fit the requirements for either academic studies or industrial applications thus become especially important. In this article, four core effects were emphasized, several misconceptions on HEAs were clarified, and several routes for future HEA research and development were suggested.

  2. Ecological models supporting environmental decision making: a strategy for the future.

    PubMed

    Schmolke, Amelie; Thorbek, Pernille; DeAngelis, Donald L; Grimm, Volker

    2010-08-01

    Ecological models are important for environmental decision support because they allow the consequences of alternative policies and management scenarios to be explored. However, current modeling practice is unsatisfactory. A literature review shows that the elements of good modeling practice have long been identified but are widely ignored. The reasons for this might include lack of involvement of decision makers, lack of incentives for modelers to follow good practice, and the use of inconsistent terminologies. As a strategy for the future, we propose a standard format for documenting models and their analyses: transparent and comprehensive ecological modeling (TRACE) documentation. This standard format will disclose all parts of the modeling process to scrutiny and make modeling itself more efficient and coherent. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  3. A Survey of Strategies to Modulate the Bone Morphogenetic Protein Signaling Pathway: Current and Future Perspectives

    PubMed Central

    2016-01-01

    Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the TGF-β family of ligands and are unequivocally involved in regulating stem cell behavior. Appropriate regulation of canonical BMP signaling is critical for the development and homeostasis of numerous human organ systems, as aberrations in the BMP pathway or its regulation are increasingly associated with diverse human pathologies. In this review, we provide a wide-perspective on strategies that increase or decrease BMP signaling. We briefly outline the current FDA-approved approaches, highlight emerging next-generation technologies, and postulate prospective avenues for future investigation. We also detail how activating other pathways may indirectly modulate BMP signaling, with a particular emphasis on the relationship between the BMP and Activin/TGF-β pathways. PMID:27433166

  4. Are drug-eluting stents the future of SFA treatment?

    PubMed

    Bosiers, M; Deloose, K; Keirse, K; Verbist, J; Peeters, P

    2010-02-01

    Drug-eluting stent (DES) technology was developed to prevent early thrombosis and late luminal loss to potentially improve long-term patency rates. Although favorable DES results have recently become available with the Zilver PTX and STRIDES studies, the high price of DES is a major drawback for this technology to become the golden standard for peripheral endovascular therapy in de novo femoro-popliteal (FP) lesions. Nevertheless, DES has the potential to make the difference and to establish itself as an important treatment option in patients presenting with TASC C&D FP lesions who are at high-risk for surgery and for the treatment of in-stent restenosis, where until now, no valuable treatment option has proven to be beneficial.

  5. Future Directions for Pharmacotherapies for Treatment-resistant Bipolar Disorder

    PubMed Central

    Dodd, Seetal; Fernandes, Brisa S.; Dean, Olivia M.

    2015-01-01

    Current pharmacological treatments for bipolar disorder (BD) are limited and efficacy has historically been discovered through serendipity. There is now scope for new drug development, focused on the underlying biology of BD that is not targeted by current therapies. The need for novel treatments is urgent when considering treatment resistant BD, where current therapies have failed. While established drugs targeting the monoamine systems continue to be worthwhile, new biological targets including inflammatory and oxidative an nitrosative pathways, apoptotic and neurotrophic pathways, mitochondrial pathways, the N-methyl-Daspartate (NMDA)–receptor complex, the purinergic system, neuropeptide system, cholinergic system and melatonin pathways are all being identified as potential anchors for the discovery of new agents. Many agents are experimental and efficacy data is limited, however further investigation may provide a new line for drug discovery, previously stalled by lack of corporate interest. PMID:26467413

  6. Treatment strategies in early rheumatoid arthritis and prevention of rheumatoid arthritis.

    PubMed

    Demoruelle, M Kristen; Deane, Kevin D

    2012-10-01

    Data now suggest that current strategies in the treatment of rheumatoid arthritis (RA) should focus on early identification and diagnosis, followed by early initiation of DMARD therapy. Initiation of treatment in early RA-ideally, less than 3-6 months after symptom onset-improves the success of achieving disease remission and reduces joint damage and disability. While the optimal treatment regimen in early RA is unclear, use of initial DMARD mono- or combination therapy with prompt escalation to achieve low disease activity or remission is an appropriate approach. Ultimately, the goal of RA management should be the prevention of inflammatory joint disease and, thereby, prevention of disability. To date, studies have shown that pharmacologic interventions can delay progression from undifferentiated inflammatory arthritis to classifiable RA. However, further investigation is needed to identify asymptomatic individuals at high risk for future RA and to intervene early enough in the pathogenesis of RA to prevent progression to clinical disease.

  7. Treatment Strategies in Early Rheumatoid Arthritis and Prevention of Rheumatoid Arthritis

    PubMed Central

    Demoruelle, M. Kristen

    2013-01-01

    Data now suggest that current strategies in the treatment of rheumatoid arthritis (RA) should focus on early identification and diagnosis, followed by early initiation of DMARD therapy. Initiation of treatment in early RA—ideally, less than 3–6 months after symptom onset—improves the success of achieving disease remission and reduces joint damage and disability. While the optimal treatment regimen in early RA is unclear, use of initial DMARD mono- or combination therapy with prompt escalation to achieve low disease activity or remission is an appropriate approach. Ultimately, the goal of RA management should be the prevention of inflammatory joint disease and, thereby, prevention of disability. To date, studies have shown that pharmacologic interventions can delay progression from undifferentiated inflammatory arthritis to classifiable RA. However, further investigation is needed to identify asymptomatic individuals at high risk for future RA and to intervene early enough in the pathogenesis of RA to prevent progression to clinical disease. PMID:22773387

  8. Behavioral side effects of pediatric acute lymphoblastic leukemia treatment: the role of parenting strategies.

    PubMed

    Williams, Lauren K; Lamb, Karen E; McCarthy, Maria C

    2014-11-01

    Behavioral and emotional difficulties are a recognised side effect of childhood acute lymphoblastic leukemia (ALL) treatment. Modifiable factors, such as parenting strategies, may be an appropriate target for interventions to assist families with managing their child's behavior, potentially leading to improved psychosocial and clinical outcomes. This study examined whether parenting strategies are associated with child behavioral and emotional problems in a pediatric oncology context, with the aim of establishing whether parenting is a potential modifiable target for psychosocial intervention. Participants included 73 parents of children aged 2-6 years who were either (i) in the maintenance phase of treatment for ALL at the Royal Children's Hospital Children's Cancer Centre, Melbourne (N = 43), or (ii) had no major medical history (healthy control group) (N = 30). Participants completed psychometrically validated questionnaires that assessed parenting strategies and child emotional and behavioral problems. Results revealed that the ALL group parents reported higher lax parenting and more spoiling and bribing of their child than the healthy control group. Results from regression models indicated that, after controlling for the significant contribution of illness status and child age on child emotional and behavioral difficulties, parental laxness and parental overprotection were significantly associated with child emotional and behavioral difficulties. Supporting parents to minimise sub-optimal parenting strategies, particularly lax parenting, may offer a fruitful avenue for future research directed toward modifiable factors associated with managing child emotional and behavioral problems in a pediatric oncology context. © 2014 Wiley Periodicals, Inc.

  9. Treatment of Prosthetic Valve Thrombosis: Current Evidence and Future Directions

    PubMed Central

    Biteker, Murat; Altun, Ibrahim; Basaran, Ozcan; Dogan, Volkan; Yildirim, Birdal; Ergun, Gokhan

    2015-01-01

    Prosthetic heart valve thrombosis (PVT) is a rare but serious complication with high morbidity and mortality. The optimal treatment of the PVT is controversial and depends on thrombus location and size, the patient’s functional class, the risk of surgery or thrombolysis, and the clinician’s experience. Although surgical therapy has been the traditional therapeutic approach, studies with low-dose and slow-infusion rates of thrombolytic agents have revealed excellent results. This article reviews the various treatment options in patient with PVT. PMID:26566406

  10. Hazardous waste, impact on health and environment for development of better waste management strategies in future in India.

    PubMed

    Misra, Virendra; Pandey, S D

    2005-04-01

    Industry has become an essential part of modern society, and waste production is an inevitable outcome of the developmental activities. A material becomes waste when it is discarded without expecting to be compensated for its inherent value. These wastes may pose a potential hazard to the human health or the environment (soil, air, water) when improperly treated, stored, transported or disposed off or managed. Currently in India even though hazardous wastes, emanations and effluents are regulated, solid wastes often are disposed off indiscriminately posing health and environmental risk. In view of this, management of hazardous wastes including their disposal in environment friendly and economically viable way is very important and therefore suggestions are made for developing better strategies. Out of the various categories of the wastes, solid waste contributes a major share towards environmental degradation. The present paper outlines the nature of the wastes, waste generating industries, waste characterization, health and environmental implications of wastes management practices, steps towards planning, design and development of models for effective hazardous waste management, treatment, approaches and regulations for disposal of hazardous waste. Appraisal of the whole situation with reference to Indian scenario is attempted so that a better cost-effective strategies for waste management be evolved in future.

  11. Nanotechnology-based strategies for treatment of ocular disease.

    PubMed

    Weng, Yuhua; Liu, Juan; Jin, Shubin; Guo, Weisheng; Liang, Xingjie; Hu, Zhongbo

    2017-05-01

    Ocular diseases include various anterior and posterior segment diseases. Due to the unique anatomy and physiology of the eye, efficient ocular drug delivery is a great challenge to researchers and pharmacologists. Although there are conventional noninvasive and invasive treatments, such as eye drops, injections and implants, the current treatments either suffer from low bioavailability or severe adverse ocular effects. Alternatively, the emerging nanoscience and nanotechnology are playing an important role in the development of novel strategies for ocular disease therapy. Various active molecules have been designed to associate with nanocarriers to overcome ocular barriers and intimately interact with specific ocular tissues. In this review, we highlight the recent attempts of nanotechnology-based systems for imaging and treating ocular diseases, such as corneal d iseases, glaucoma, retina diseases, and choroid diseases. Although additional work remains, the progress described herein may pave the way to new, highly effective and important ocular nanomedicines.

  12. [Surgical treatment strategy for flatfoot related with accessory navicular].

    PubMed

    Deng, Yin-shuan; Gao, Qiu-ming; Zhen, Ping; Tang, Kang-lai

    2015-02-01

    Accessory navicular source flatfoot is one of the foot deformity of clinical common disease,its treatment method is more controversial, differences in clinical efficacy of different surgical methods, according to accessory navicular source flatfoot symptoms of surgical treatment,there is no uniform standard, around a pair of accessory navicular excision how to reconstruct the arch produced a series of operation methods, the clinical curative effect of different operative methods produce also different, how to develop the operation strategy, choose operation method, and after acessory navicular excision whether to rebuild posterior tibial tendon, how to rebuild, the problems such as how to rebuild is the research hotspot and difficulty, looking forward to further research.

  13. Future advances and areas of future focus in the treatment of sport-related concussion.

    PubMed

    McCrory, Paul

    2011-01-01

    The occurrence and management of sports concussion provokes more debate and concern than virtually all other sports injuries combined. In the past 3 decades, clinicians have gone from mostly anecdotal strategies to an international consensus-based approach and the early evolution of evidence-based practice. There is increasing engagement by mainstream neuroscientists in this field, which had previously been dominated by sports team physicians. However, the interchange has largely taken place in the media rather than through scientific journals. Legislators have proposed regulatory measures that restrict medical management of concussion in ways that apply to no other medical condition. This paper examines some of the key areas that are likely to be the focus of research in the next few years.

  14. A current analysis of chemotherapy strategies for the treatment of human African trypanosomiasis

    PubMed Central

    Babokhov, Peter; Sanyaolu, Adekunle O; Oyibo, Wellington A; Fagbenro-Beyioku, Adetayo F; Iriemenam, Nnaemeka C

    2013-01-01

    Despite the recent advances in drug research, finding a safe, effective, and easy to use chemotherapy for human African trypanosomiasis (HAT) remains a challenging task. The four current anti-trypanosomiasis drugs have major disadvantages that limit more widespread use of these drugs in the endemic regions of sub-Saharan Africa. Pentamidine and suramin are limited by their effectiveness against the only first stage of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, respectively. In addition, melarsoprol and eflornithine (two second stage drugs) each have disadvantages of their own. The former is toxic and has increasing treatment failures while the latter is expensive, laborious to administer, and lacks efficacy against T. b. rhodesiense. Furthermore, melarsoprol’s toxicity and decreasing efficacy are glaring problems and phasing out the drug as a frontline treatment against T. b. gambiense is now possible with the emergence of competent, safe combination chemotherapies such as nifurtimox–eflornithine combination treatment (NECT). The future of eflornithine, on the other hand, is more promising. The drug is useful in the context of combination chemotherapy and potential orally administered analogues. Due to the limits of monotherapies, greater emphasis should be placed on the research and development of combination chemotherapies, based on the successful clinical tests with NECT and its current use as a frontline anti-trypanosomiasis treatment. This review discussed the current and future chemotherapy strategies for the treatment of HAT. PMID:23916333

  15. A current analysis of chemotherapy strategies for the treatment of human African trypanosomiasis.

    PubMed

    Babokhov, Peter; Sanyaolu, Adekunle O; Oyibo, Wellington A; Fagbenro-Beyioku, Adetayo F; Iriemenam, Nnaemeka C

    2013-07-01

    Despite the recent advances in drug research, finding a safe, effective, and easy to use chemotherapy for human African trypanosomiasis (HAT) remains a challenging task. The four current anti-trypanosomiasis drugs have major disadvantages that limit more widespread use of these drugs in the endemic regions of sub-Saharan Africa. Pentamidine and suramin are limited by their effectiveness against the only first stage of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, respectively. In addition, melarsoprol and eflornithine (two second stage drugs) each have disadvantages of their own. The former is toxic and has increasing treatment failures while the latter is expensive, laborious to administer, and lacks efficacy against T. b. rhodesiense. Furthermore, melarsoprol's toxicity and decreasing efficacy are glaring problems and phasing out the drug as a frontline treatment against T. b. gambiense is now possible with the emergence of competent, safe combination chemotherapies such as nifurtimox-eflornithine combination treatment (NECT). The future of eflornithine, on the other hand, is more promising. The drug is useful in the context of combination chemotherapy and potential orally administered analogues. Due to the limits of monotherapies, greater emphasis should be placed on the research and development of combination chemotherapies, based on the successful clinical tests with NECT and its current use as a frontline anti-trypanosomiasis treatment. This review discussed the current and future chemotherapy strategies for the treatment of HAT.

  16. Empirically Supported Treatment Endeavour: A Successful Future or Inevitable Debacle?

    ERIC Educational Resources Information Center

    Foley, Jessica M.

    2004-01-01

    The Empirically Supported Treatment (EST) endeavour began with and has persisted through prodigious skepticism among practising clinical psychologists. Despite such criticism, however, the advent of managed care guidelines, growing emphasis on biological psychiatry, promotion of scientific interests, and the need for better patient care have…

  17. Family treatment of child anxiety: outcomes, limitations and future directions.

    PubMed

    Creswell, Cathy; Cartwright-Hatton, Sam

    2007-09-01

    Anxiety of childhood is a common and serious condition. The past decade has seen an increase in treatment-focussed research, with recent trials tending to give greater attention to parents in the treatment process. This review examines the efficacy of family-based cognitive behaviour therapy and attempts to delineate some of the factors that might have an impact on its efficacy. The choice and timing of outcome measure, age and gender of the child, level of parental anxiety, severity and type of child anxiety and treatment format and content are scrutinised. The main conclusions are necessarily tentative, but it seems likely that Family Cognitive Behaviour Therapy (FCBT) is superior to no treatment, and, for some outcome measures, also superior to Child Cognitive Behaviour Therapy (CCBT). Where FCBT is successful, the results are consistently maintained at follow-up. It appears that where a parent is anxious, and this is not addressed, outcomes are less good. However, for children of anxious parents, FCBT is probably more effective than CCBT. What is most clear is that large, well-designed studies, examining these factors alone and in combination, are now needed.

  18. Sustainability of irrigated crops under future climate: the interplay of irrigation strategies and cultivar responses

    NASA Astrophysics Data System (ADS)

    De Lorenzi, F.; Bonfante, A.; Alfieri, S.; Patanè, C.; Basile, A.; Di Tommasi, P.; Monaco, E.; Menenti, M.

    2012-04-01

    Climate evolution will cause significant changes in the quality and availability of water resources, affecting many sectors including food production, where available water resources for irrigation play a crucial role. Strategies focused on managing and conserving water are one way to deal with the impact; moreover concurring adaptation measurements will be needed to cope with the foreseen decline of water resource. This work deals with i) the impacts of climate change on water requirements of an horticultural crop, determined in an irrigated district in Southern Italy, ii) the possible irrigation scheduling options and their sustainability in the future, iii) the adaptation measurements that can be undertaken to protect production, relying on intra-specific biodiversity of agricultural crops. Two climate scenarios were considered: present climate (1961-90) and future climate (2021-2050), the former from climatic statistics, and the latter from statistical downscaling of general circulation models (AOGCM). Climatic data set consists of daily time series of maximum and minimum temperature, and rainfall on a grid with spatial resolution of 35 km. The analysis of climate scenarios showed that significant increases in summer maximum daily temperature could be expected in 2021-2050 period. Soil water regime was determined by means of a mechanistic model (SWAP) of water flow in the soil-plant-atmosphere system. Twenty? soil units were identified in the district (in Sele Plain, Campania Region) and simulations were performed accounting for hydro-pedological properties of different soil units. Parameters of a generic tomato crop, in a rotation typical of the area, were used in simulations. Soil water balance was simulated in the present and future climate, both with optimal water availability and under constrains that irrigation schemes will pose. Indicators of soil water availability were calculated, in terms of soil water or evapotranspiration deficit. For several tomato

  19. Exercise as an augmentation strategy for treatment of major depression.

    PubMed

    Trivedi, Madhukar H; Greer, Tracy L; Grannemann, Bruce D; Chambliss, Heather O; Jordan, Alexander N

    2006-07-01

    The use of augmentation strategies among patients with major depression is increasing because rates of complete remission with standard antidepressant monotherapy are quite low. Clinical and neurobiological data suggest that exercise may be a good candidate for use as an augmentation treatment for depression. This pilot study examined the use of exercise to augment antidepressant medication in patients with major depression. Seventeen patients with incomplete remission of depressive symptoms began a 12-week exercise program while continuing their antidepressant medication (unchanged in type or dose). Individual exercise prescriptions were calculated based on an exercise dose consistent with currently recommended public health guidelines. The exercise consisted of both supervised and home-based sessions. The 17-item Hamilton Rating Scale for Depression (HRSD17) and the Inventory of Depressive Symptomatology-Self-Report (IDS-SR30) were used to assess symptoms of depression on a weekly basis. Intent-to-treat analyses yielded significant decreases on both the HRSD17 (5.8 points, p < 0.008) and IDS-SR30 (13.9 points, p < 0.002). For patients who completed the study (n = 8), HRSD17 scores decreased by 10.4 points and IDS-SR30 scores decreased by 18.8 points. This study provides preliminary evidence for exercise as an effective augmentation treatment for antidepressant medication. This is a lower-cost augmentation strategy that has numerous health benefits and may further reduce depressive symptoms in partial responders to antidepressant treatment. Practical tips on how practitioners can use exercise to enhance antidepressant treatment are discussed. Longer-term use of exercise is also likely to confer additional health benefits for this population.

  20. Clean option: Berkeley Pit water treatment and resource recovery strategy

    SciTech Connect

    Gerber, M.A.; Orth, R.J.; Elmore, M.R.; Monzyk, B.F.

    1995-09-01

    The US Department of Energy (DOE), Office of Technology Development, established the Resource Recovery Project (RRP) in 1992 as a five-year effort to evaluate and demonstrate multiple technologies for recovering water, metals, and other industrial resources from contaminated surface and groundwater. Natural water resources located throughout the DOE complex and the and western states have been rendered unusable because of contamination from heavy metals. The Berkeley Pit, a large, inactive, open pit copper mine located in Butte, Montana, along with its associated groundwater system, has been selected by the RRP for use as a feedstock for a test bed facility located there. The test bed facility provides the infrastructure needed to evaluate promising technologies at the pilot plant scale. Data obtained from testing these technologies was used to assess their applicability for similar mine drainage water applications throughout the western states and at DOE. The objective of the Clean Option project is to develop strategies that provides a comprehensive and integrated approach to resource recovery using the Berkeley Pit water as a feedstock. The strategies not only consider the immediate problem of resource recovery from the contaminated water, but also manage the subsequent treatment of all resulting process streams. The strategies also employ the philosophy of waste minimization to optimize reduction of the waste volume requiring disposal, and the recovery and reuse of processing materials.

  1. Drug abstinence: exploring animal models and behavioral treatment strategies.

    PubMed

    Peck, Joshua A; Ranaldi, Robert

    2014-05-01

    An enormous amount of resources has been devoted to the development of pharmacotherapies for drug addiction, with relatively little or no long-term success reported. The current review argues that a successful drug addiction treatment program will likely be one that focuses on both the neural mechanisms and the environmental contingencies that mediate drug use. Further, because the neural mechanisms and environmental factors that support abstinence in humans are similar in laboratory animals, several animal models of abstinence and relapse have been developed. Thus, this review also compares the similarities in the mechanisms that lead to abstinence between animals and humans. We evaluate the construct and face validities of the behavioral strategies that help support human drug abstinence. Further, we crucially evaluate animal models by assessing their validity and utility in addressing human behavior that leads to long-term abstinence. We found that the behavioral strategies with the greatest likelihood of supporting long-term abstinence are those that are carried out in drug addicts' natural setting(s) and while drug is readily available. Further, the behavioral strategies that may be most successful in supporting abstinence in humans are those that employ both positive consequences for abstinent related behavior and negative consequences for continued drug seeking or taking. Moreover, the animal models of abstinence and relapse that more closely represent the factors that support long-term abstinence in humans are those that limit their use of extinction or forced abstinence and present negative consequences for drug seeking and taking.

  2. ICT-based health information services for elderly people: past experiences, current trends, and future strategies.

    PubMed

    Marschollek, Michael; Mix, Stefan; Wolf, Klaus-H; Effertz, Beate; Haux, Reinhold; Steinhagen-Thiessen, Elisabeth

    2007-12-01

    Although health information is readily available on the Internet and has changed the way people deal with their health in many ways, the retrieval of relevant information remains problematic, especially for elderly people. With a focus on elderly people, this paper summarizes current trends in consumer health informatics, discusses past and present initiatives providing health-information services, and proposes a future strategy for the design of sustainable services. A systematic literature review and a review of past German and EU projects concerned with health information services for elderly people are given. Many publications focus on health information services for specific diseases and on their quality and semantic accessibility, yet few deal with presenting and customizing health information for elderly and disabled people. Past experiences from Germany suggest that very often the specific needs of this target group are not met, and therefore accessibility remains largely hypothetical. We propose a strategy with five key points for the design of sustainable health-information services for elderly people. More research is needed to customize web-based health information services to the needs of the user group that needs them most urgently - elderly and disabled people.

  3. Optimizing future treatment of enterococcal infections: attacking the biofilm?

    PubMed

    Paganelli, Fernanda L; Willems, Rob J; Leavis, Helen L

    2012-01-01

    Enterococcus faecalis and Enterococcus faecium are among the leading causative agents of nosocomial infections and are infamous for their resistance to many antibiotics. They cause difficult-to-treat infections, often originating from biofilm-mediated infections associated with implanted medical devices or endocarditis. Biofilms protect bacteria against antibiotics and phagocytosis, and physical removal of devices or infected tissue is often needed but is frequently not possible. Currently there are no clinically available compounds that disassemble biofilms. In this review we discuss all known structural and regulatory genes involved in enterococcal biofilm formation, the compounds directed against biofilm formation that have been studied, and potentially useful targets for future drugs to treat enterococcal biofilm-associated infections.

  4. Real-time nutrient monitoring in rivers: adaptive sampling strategies, technological challenges and future directions

    NASA Astrophysics Data System (ADS)

    Blaen, Phillip; Khamis, Kieran; Lloyd, Charlotte; Bradley, Chris

    2016-04-01

    Excessive nutrient concentrations in river waters threaten aquatic ecosystem functioning and can pose substantial risks to human health. Robust monitoring strategies are therefore required to generate reliable estimates of river nutrient loads and to improve understanding of the catchment processes that drive spatiotemporal patterns in nutrient fluxes. Furthermore, these data are vital for prediction of future trends under changing environmental conditions and thus the development of appropriate mitigation measures. In recent years, technological developments have led to an increase in the use of continuous in-situ nutrient analysers, which enable measurements at far higher temporal resolutions than can be achieved with discrete sampling and subsequent laboratory analysis. However, such instruments can be costly to run and difficult to maintain (e.g. due to high power consumption and memory requirements), leading to trade-offs between temporal and spatial monitoring resolutions. Here, we highlight how adaptive monitoring strategies, comprising a mixture of temporal sample frequencies controlled by one or more 'trigger variables' (e.g. river stage, turbidity, or nutrient concentration), can advance our understanding of catchment nutrient dynamics while simultaneously overcoming many of the practical and economic challenges encountered in typical in-situ river nutrient monitoring applications. We present examples of short-term variability in river nutrient dynamics, driven by complex catchment behaviour, which support our case for the development of monitoring systems that can adapt in real-time to rapid environmental changes. In addition, we discuss the advantages and disadvantages of current nutrient monitoring techniques, and suggest new research directions based on emerging technologies and highlight how these might improve: 1) monitoring strategies, and 2) understanding of linkages between catchment processes and river nutrient fluxes.

  5. Treatment of Thrombotic Antiphospholipid Syndrome: The Rationale of Current Management—An Insight into Future Approaches

    PubMed Central

    Ubiali, Tania; Meroni, Pier Luigi

    2015-01-01

    Vascular thrombosis and pregnancy morbidity represent the clinical manifestations of antiphospholipid syndrome (APS), which is serologically characterized by the persistent positivity of antiphospholipid antibodies (aPL). Antiplatelet and anticoagulant agents currently provide the mainstay of APS treatment. However, the debate is still open: controversies involve the intensity and the duration of anticoagulation and the treatment of stroke and refractory cases. Unfortunately, the literature cannot provide definite answers to these controversial issues as it is flawed by many limitations, mainly due to the recruitment of patients not fulfilling laboratory and clinical criteria for APS. The recommended therapeutic management of different aPL-related clinical manifestations is hereby presented, with a critical appraisal of the evidence supporting such approaches. Cutting edge therapeutic strategies are also discussed, presenting the pioneer reports about the efficacy of novel pharmacological agents in APS. Thanks to a better understanding of aPL pathogenic mechanisms, new therapeutic targets will soon be explored. Much work is still to be done to unravel the most controversial issues about APS management: future studies are warranted to define the optimal management according to aPL risk profile and to assess the impact of a strict control of cardiovascular risk factors on disease control. PMID:26075289

  6. Treatment of Thrombotic Antiphospholipid Syndrome: The Rationale of Current Management-An Insight into Future Approaches.

    PubMed

    Chighizola, Cecilia Beatrice; Ubiali, Tania; Meroni, Pier Luigi

    2015-01-01

    Vascular thrombosis and pregnancy morbidity represent the clinical manifestations of antiphospholipid syndrome (APS), which is serologically characterized by the persistent positivity of antiphospholipid antibodies (aPL). Antiplatelet and anticoagulant agents currently provide the mainstay of APS treatment. However, the debate is still open: controversies involve the intensity and the duration of anticoagulation and the treatment of stroke and refractory cases. Unfortunately, the literature cannot provide definite answers to these controversial issues as it is flawed by many limitations, mainly due to the recruitment of patients not fulfilling laboratory and clinical criteria for APS. The recommended therapeutic management of different aPL-related clinical manifestations is hereby presented, with a critical appraisal of the evidence supporting such approaches. Cutting edge therapeutic strategies are also discussed, presenting the pioneer reports about the efficacy of novel pharmacological agents in APS. Thanks to a better understanding of aPL pathogenic mechanisms, new therapeutic targets will soon be explored. Much work is still to be done to unravel the most controversial issues about APS management: future studies are warranted to define the optimal management according to aPL risk profile and to assess the impact of a strict control of cardiovascular risk factors on disease control.

  7. The HIV treatment cascade and care continuum: updates, goals, and recommendations for the future.

    PubMed

    Kay, Emma Sophia; Batey, D Scott; Mugavero, Michael J

    2016-01-01

    The HIV care continuum is a framework that models the dynamic stages of HIV care. The continuum consists of five main steps, which, at the population level, are depicted cross-sectionally as the HIV treatment cascade. These steps include diagnosis, linkage to care (LTC), retention in care (RiC), adherence to antiretroviral therapy (ART), and viral suppression. Although the HIV treatment cascade is represented as a linear, unidirectional framework, persons living with HIV (PLWH) often experience the care continuum in a less streamlined fashion, skip steps altogether, or even exit the continuum for a period of time and regress to an earlier stage. The proportion of PLWH decreases at each successive step of the cascade, beginning with an estimated 86% who are diagnosed and dropping dramatically to approximately 30% of PLWH who are virally suppressed in the United States (US). In this current issues review, we describe each step in the cascade, discuss targeted interventions that address weak points in the continuum, review domestic and international policies that help shape and direct HIV care strategies, and conclude with recommendations and future directions for HIV providers and policymakers. While we primarily examine issues related to domestic HIV care in the US, we also discuss international applications of the continuum in order to provide broader context.

  8. Enhancement of Psychosocial Treatment with D-Cycloserine: Models, Moderators, and Future Directions

    PubMed Central

    Otto, Michael W.; Kredlow, M. Alexandra; Smits, Jasper A. J.; Hofmann, Stefan G.; Tolin, David F.; de Kleine, Rianne A.; van Minnen, Agnes; Evins, A. Eden; Pollack, Mark H.

    2015-01-01

    Advances in the understanding of the neurobiology of fear extinction resulted in the development of d-cycloserine (DCS), a partial glutamatergic N-methyl-D-aspartate agonist, as an augmentation strategy for exposure treatment. We review a decade of research that has focused on the efficacy of DCS for augmenting the mechanisms (e.g., fear extinction) and outcome of exposure treatment across the anxiety disorders. Following a series of small-scale studies offering strong support for this clinical application, more recent larger-scale studies have yielded mixed results, with some showing weak or no effects. We discuss possible explanations of the mixed findings, pointing to both patient and session (i.e., learning experiences) characteristics as possible moderators of efficacy, and offer directions for future research in this area. We also review recent studies that have aimed to extend the work on DCS augmentation of exposure therapy for the anxiety disorders to DCS enhancement of learning-based interventions for addiction, anorexia nervosa, schizophrenia, and depression. Here, we attend to both DCS effects on facilitating therapeutic outcomes and additional therapeutic mechanisms beyond fear extinction (e.g., appetitive extinction, hippocampal-dependent learning). PMID:26520240

  9. [Changes in the treatment strategy of primary gastric lymphoma].

    PubMed

    Tóth, Imre; Nagy, Zsolt; Barna, Tibor; Szucs, Géza

    2007-04-01

    Nowadays the management strategy for primary gastric lymphoma is undergoing change due to the effectiveness of chemotherapy and immunotherapy. While earlier surgical resection was the primary treatment and chemotherapy was only a follow-on procedure, at the present time this arrangement seems to have been reversed. Early stage low-grade MALT lymphoma can be treated with Helicobacter pylori eradication. Total or subtotal gastrectomy with D2 lymphadenectomy and with adjuvant chemotherapy in R1 situation is proposed up to stage II.1. The strategy is similar in the case of high-grade gastric lymphoma, but resection is useful only in those cases when one can be assured the result will be an R0 situation. With the exception of these cases, the only indication for resection is chemo-resistance. There is no reason for operating in advanced stages of the disease. The only purpose can be to manage complications. Unfortunately, the exact diagnosis is difficult. The diagnosis of lymphoma can often only be made after the operation. In the 6-year period between 1st January 2000 and 31st December 2005 we treated 38 patients for primary gastric lymphoma. Altogether 9 patients were operated on. Resection was performed in 6 cases. The diagnosis of lymphoma was known preoperatively only in one case. Nowadays surgery seems to be only secondary to chemotherapy and immuno-chemotherapy in the treatment of primary gastric MALT lymphoma. Our own cases also mirror this change.

  10. Angina pectoris: current therapy and future treatment options.

    PubMed

    Parikh, Raj; Kadowitz, Philip J

    2014-02-01

    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.

  11. Surgical Treatment for Chronic Pancreatitis: Past, Present, and Future

    PubMed Central

    Welte, Maria; Izbicki, Jakob R.; Bachmann, Kai

    2017-01-01

    The pancreas was one of the last explored organs in the human body. The first surgical experiences were made before fully understanding the function of the gland. Surgical procedures remained less successful until the discovery of insulin, blood groups, and finally the possibility of blood donation. Throughout the centuries, the surgical approach went from radical resections to minimal resections or only drainage of the gland in comparison to an adequate resection combined with drainage procedures. Today, the well-known and standardized procedures are considered as safe due to the high experience of operating surgeons, the centering of pancreatic surgery in specialized centers, and optimized perioperative treatment. Although surgical procedures have become safer and more efficient than ever, the overall perioperative morbidity after pancreatic surgery remains high and management of postoperative complications stagnates. Current research focuses on the prevention of complications, optimizing the patient's general condition preoperatively and finding the appropriate timing for surgical treatment. PMID:28819358

  12. [Gene therapy in Parkinson disease: a promising future treatment?].

    PubMed

    Golé, Claire; Reboul, Romain; Pisano, Pascale

    2011-01-01

    Parkinson disease is a neurodegenerative pathology with high incidence. Current treatments ease the symptoms but don't stop the development of the disease and aren't without any major side effects. Although this pathology is not specifically caused by genetic abnormalities, the involvement of numerous proteins in the pathophysiological process enables us to give an interest to gene therapy. This hypothesis has been upheld by positive results on animals and by five phase I trials on humans but may be attenuated by the first phase II trial recently published showing modest efficiency and multiple side effects. However, these preliminary results will need to be reinforced by more important trials in order to be sure of the safety and get efficacy data, which will allow us to give an opinion upon this new way of treatment.

  13. Future directions in the treatment of HIV-HBV coinfection.

    PubMed

    Iser, David M; Lewin, Sharon R

    2009-07-01

    Liver disease is a major cause of mortality in individuals with HIV-HBV coinfection. The pathogenesis of liver disease in this setting is unknown, but is likely to involve drug toxicity, infection of hepatic cells with both HIV and HBV, and an altered immune response to HBV. The availability of therapeutic agents that target both HIV and HBV replication enable dual viral suppression, and assessment of chronic hepatitis B is important prior to commencement of antiretroviral therapy. Greater importance is now placed on HBV DNA levels and staging of liver fibrosis, either by liver biopsy or noninvasive measurement, such as transient elastography, since significant liver fibrosis may exist in the presence of normal liver function tests. Earlier treatment of both HIV and HBV is now generally advocated and treatment is usually lifelong.

  14. Current and future medical treatments for patients with acromegaly.

    PubMed

    Maffezzoni, Filippo; Formenti, Anna Maria; Mazziotti, Gherardo; Frara, Stefano; Giustina, Andrea

    2016-08-01

    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.

  15. Advances in Risk Classification and Treatment Strategies for Neuroblastoma

    PubMed Central

    Pinto, Navin R.; Applebaum, Mark A.; Volchenboum, Samuel L.; Matthay, Katherine K.; London, Wendy B.; Ambros, Peter F.; Nakagawara, Akira; Berthold, Frank; Schleiermacher, Gudrun; Park, Julie R.; Valteau-Couanet, Dominique; Pearson, Andrew D.J.

    2015-01-01

    Risk-based treatment approaches for neuroblastoma have been ongoing for decades. However, the criteria used to define risk in various institutional and cooperative groups were disparate, limiting the ability to compare clinical trial results. To mitigate this problem and enhance collaborative research, homogenous pretreatment patient cohorts have been defined by the International Neuroblastoma Risk Group classification system. During the past 30 years, increasingly intensive, multimodality approaches have been developed to treat patients who are classified as high risk, whereas patients with low- or intermediate-risk neuroblastoma have received reduced therapy. This treatment approach has resulted in improved outcome, although survival for high-risk patients remains poor, emphasizing the need for more effective treatments. Increased knowledge regarding the biology and genetic basis of neuroblastoma has led to the discovery of druggable targets and promising, new therapeutic approaches. Collaborative efforts of institutions and international cooperative groups have led to advances in our understanding of neuroblastoma biology, refinements in risk classification, and stratified treatment strategies, resulting in improved outcome. International collaboration will be even more critical when evaluating therapies designed to treat small cohorts of patients with rare actionable mutations. PMID:26304901

  16. Tuberculosis and HIV co-infection: screening and treatment strategies.

    PubMed

    Venkatesh, Kartik K; Swaminathan, Soumya; Andrews, Jason R; Mayer, Kenneth H

    2011-06-18

    Globally, tuberculosis (TB) and HIV interact in deadly synergy. The high burden of TB among HIV-infected individuals underlies the importance of TB diagnosis, treatment and prevention for clinicians involved in HIV care. Despite expanding access to antiretroviral therapy (ART) to treat HIV infection in resource-limited settings, many individuals in need of therapy initiate ART too late and have already developed clinically significant TB by the time they present for care. Many co-infected individuals are in need of concurrent ART and anti-TB therapy, which dramatically improves survival, but also raises several management challenges, including drug interactions, shared drug toxicities and TB immune reconstitution inflammatory syndrome (IRIS). Due to the survival benefits of promptly initiating ART among all HIV-infected individuals, including those with TB, it is recommended that co-infected individuals receive treatment for both diseases, regardless of CD4+ cell count. We review current screening and treatment strategies for TB and HIV co-infection. Recent findings and ongoing studies will assist clinicians in managing the prevention and treatment of TB and HIV co-infection, which remains a major global health challenge.

  17. Advances in Risk Classification and Treatment Strategies for Neuroblastoma.

    PubMed

    Pinto, Navin R; Applebaum, Mark A; Volchenboum, Samuel L; Matthay, Katherine K; London, Wendy B; Ambros, Peter F; Nakagawara, Akira; Berthold, Frank; Schleiermacher, Gudrun; Park, Julie R; Valteau-Couanet, Dominique; Pearson, Andrew D J; Cohn, Susan L

    2015-09-20

    Risk-based treatment approaches for neuroblastoma have been ongoing for decades. However, the criteria used to define risk in various institutional and cooperative groups were disparate, limiting the ability to compare clinical trial results. To mitigate this problem and enhance collaborative research, homogenous pretreatment patient cohorts have been defined by the International Neuroblastoma Risk Group classification system. During the past 30 years, increasingly intensive, multimodality approaches have been developed to treat patients who are classified as high risk, whereas patients with low- or intermediate-risk neuroblastoma have received reduced therapy. This treatment approach has resulted in improved outcome, although survival for high-risk patients remains poor, emphasizing the need for more effective treatments. Increased knowledge regarding the biology and genetic basis of neuroblastoma has led to the discovery of druggable targets and promising, new therapeutic approaches. Collaborative efforts of institutions and international cooperative groups have led to advances in our understanding of neuroblastoma biology, refinements in risk classification, and stratified treatment strategies, resulting in improved outcome. International collaboration will be even more critical when evaluating therapies designed to treat small cohorts of patients with rare actionable mutations. © 2015 by American Society of Clinical Oncology.

  18. Treatment of retinoblastoma: current status and future perspectives.

    PubMed

    Rodriguez-Galindo, Carlos; Chantada, Guillermo L; Haik, Barrett G; Wilson, Matthew W

    2007-07-01

    Treatment of retinoblastoma must be individualized. Most patients with unilateral, non-metastatic retinoblastoma can be cured with enucleation alone. In patients with histologic risk factors, adjuvant chemotherapy is recommended, with the addition of orbital radiation for patients with trans-scleral involvement or tumor present at the level of the cut end of the optic nerve. Patients with metastases require intensive chemotherapy and consolidation with autologous hematopoietic stem cell rescue. Patients with bilateral or multifocal disease represent a major challenge. Cure of the disease is the first priority, but the therapeutic approach also has to consider eye and vision preservation. The approach is conservative, and only eyes with very advanced disease are enucleated upfront. Patients are treated with chemotherapy and intensive focal treatments, with the aim of delaying or avoiding radiation therapy and enucleation. For patients with early intraocular stage (Reese-Ellsworth groups I-III and International Groups A-B), the two-drug combination of vincristine and carboplatin is recommended. Patients with more advanced intraocular disease (Reese-Ellsworth groups IV-V and International Groups C-D) require more intensive chemotherapy. Standard of care for these patients incorporates etoposide into the regimen. Effective agents with good intraocular penetration, such as topotecan, are being investigated. Because most failures are secondary to progression of the vitreous seeds, subconjunctival carboplatin is added in cases with poor response of the vitreous tumors. Patients must be monitored very closely, with examinations under anesthesia every 4 to 6 weeks, and focal treatments are applied during the procedure. These include cryotherapy for small anterior tumors, thermotherapy and laser photocoagulation for small posterior tumors, and brachytherapy for larger tumors. New treatment approaches under development include the refinement of periocular chemotherapy

  19. Overactive Bladder and the β3-Adrenoceptor Agonists: Current Strategy and Future Prospects.

    PubMed

    Giarenis, Ilias; Robinson, Dudley; Cardozo, Linda

    2015-10-01

    Overactive bladder (OAB) is a clinical syndrome describing the symptom complex of urgency, with or without urgency incontinence, and is usually associated with frequency and nocturia. It is a common, under-diagnosed and therefore under-treated condition that can have a detrimental effect on physical functioning and psychological well-being. Initial treatment of OAB includes lifestyle advice, behavioural modifications, bladder retraining and pelvic floor muscle training, usually in combination with antimuscarinic agents. The β3-adrenoceptor agonist mirabegron is the first of a new class of drugs that are now competing with the more established antimuscarinics for the treatment of OAB. Our review focuses on the mode of action, efficacy and tolerability of mirabegron. The place of β3-adrenoceptor agonists in the treatment algorithm of OAB is discussed, considering the adverse events associated with antimuscarinics. Drug therapy tailored to different population groups appears a promising future prospect. Development of other β3-adrenoceptor agonists is expected, and combination therapy regimens might revolutionise the treatment of OAB.

  20. Current and future treatments for malignant pheochromocytoma and sympathetic paraganglioma.

    PubMed

    Jimenez, Camilo; Rohren, Eric; Habra, Mouhammed Amir; Rich, Thereasa; Jimenez, Paola; Ayala-Ramirez, Montserrat; Baudin, Eric

    2013-08-01

    Pheochromocytomas (PHs) and sympathetic paragangliomas (SPGs) are rare neuroendocrine tumors. Approximately 17 % of these tumors are malignant, but because no molecular or histologic markers for malignancy exist, patients are often diagnosed with malignant PHs or SPGs after unresectable disease has formed. Patients with progressive metastatic tumors and overwhelming symptoms are currently treated with systemic chemotherapy and radiopharmaceutical agents such as metaiodobenzylguanidine. These therapies lead to partial radiographic response, disease stabilization, and symptomatic improvement in approximately 40 % of patients, and systemic chemotherapy is associated with a modest improvement in overall survival duration. However, over the past decade, substantial progress has been made in clinical, biochemical, and radiographic diagnosis of PHs and SPGs. Approximately 50 % of patients with malignant PHs and SPGs have been found to carry hereditary germline mutations in the succinate dehydrogenase subunit B gene (SDHB), and anti-angiogenic agents such as sunitinib have been found to potentially play a role in the treatment of malignant disease, especially in patients with SDHB mutations. In some patients, treatment with sunitinib has been associated with partial radiographic response, disease stabilization, decreased fluorodeoxyglucose uptake on positron emission tomography, and improved blood pressure control. These findings have led to the development of prospective clinical trials of new targeted therapies for metastatic disease. Here, we provide an updated review of the clinical and genetic predictors of malignant disease, radiographic diagnosis of malignant disease, and information from the most relevant studies of systemic therapies, as well as proposed treatment guidelines for patients with metastatic or potentially malignant PHs and SPGs.

  1. Current primary open-angle glaucoma treatments and future directions

    PubMed Central

    Beidoe, Gabriel; Mousa, Shaker A

    2012-01-01

    Primary open-angle glaucoma (POAG) is a leading cause of blindness with no known cure. Management of the disease focuses on lowering intraocular pressure (IOP) with current classes of drugs like prostaglandin analogs, beta-blockers, alpha-agonists, and carbonic anhydrase inhibitors. These treatments have not helped all patients. Some patients continue to experience deterioration in the optic nerve even though their IOPs are within the normal range. New views have surfaced about other pathophysiological processes (such as oxidative stress, vascular dysfunction, and retinal cell apoptosis) being involved in POAG progression, and adjunctive treatments with drugs like memantine, bis(7)-tacrine, nimodipine, and mirtogenol are advocated. This review examines the current and proposed treatments for POAG. Some of the proposed drugs (bis(7)-tacrine, nimodipine, vitamin E, and others) have shown good promise, mostly as monotherapy in various clinical trials. It is recommended that both the current and proposed drugs be put through further robust trials in concurrent administration and evaluated. PMID:23118520

  2. Osteogenesis imperfecta: from diagnosis and multidisciplinary treatment to future perspectives.

    PubMed

    Bregou Bourgeois, Aline; Aubry-Rozier, Bérengère; Bonafé, Luisa; Laurent-Applegate, Lee; Pioletti, Dominique P; Zambelli, Pierre-Yves

    2016-01-01

    Osteogenesis imperfecta is an inherited connective tissue disorder with wide phenotypic and molecular heterogeneity. A common issue associated with the molecular abnormality is a disturbance in bone matrix synthesis and homeostasis inducing bone fragility. In very early life, this can lead to multiple fractures and progressive bone deformities, including long bone bowing and scoliosis. Multidisciplinary management improves quality of life for patients with osteogenesis imperfecta. It consists of physical therapy, medical treatment and orthopaedic surgery as necessary. Medical treatment consists of bone-remodelling drug therapy. Bisphosphonates are widely used in the treatment of moderate to severe osteogenesis imperfecta, from infancy to adulthood. Other more recent drug therapies include teriparatide and denosumab. All these therapies target the symptoms and have effects on the mechanical properties of bone due to modification of bone remodelling, therefore influencing skeletal outcome and orthopaedic surgery. Innovative therapies, such as progenitor and mesenchymal stem cell transplantation, targeting the specific altered pathway rather than the symptoms, are in the process of development.

  3. The cardiometabolic effect of current management of polycystic ovary syndrome: strategies of prevention and treatment.

    PubMed

    Baldani, Dinka Pavicic; Skrgatic, Lana; Ougouag, Roya; Kasum, Miro

    2017-09-23

    Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder amongst women of reproductive age, which is characterized by reproductive and cardiometabolic disturbances with long-term health repercussions. Insulin resistance (IR), impaired glucose tolerance, type 2 diabetes mellitus (DM2), obesity and dyslipidemia occur more in women with PCOS than in age-comparable women without PCOS. Long term data regarding risks or benefits of medical intervention for metabolic dysfunction of PCOS are lacking. Therapies, such as oral contraceptives (OCPs) and anti-androgenic medications used to manage the reproductive manifestations of PCOS, may themselves be the cause of cardiometabolic perturbations. Hence, strategies regarding the management of reproductive issues in PCOS encompass a patient-specific tailored approach. Factors that influence the cardiometabolic side effects arising during treatment of the reproductive manifestations of PCOS (hirsutism/anovulation) are also discussed in this paper in order to build future strategies to minimize the overall cardiometabolic risk.

  4. Strategies used by breast cancer survivors to address work-related limitations during and after treatment.

    PubMed

    Sandberg, Joanne C; Strom, Carla; Arcury, Thomas A

    2014-01-01

    The primary objective of this exploratory study was to delineate the broad range of adjustments women breast cancer survivors draw upon to minimize cancer-related limitations at the workplace. The study also analyzed whether survivors used strategies to address work-related limitations in isolation or in combination with other strategies, and whether they used formal or informal strategies. Semi-structured, in-depth interviews were conducted with 14 women who were employed at the time of diagnosis of breast cancer and who continued to work during treatment or returned to work. Interviews were conducted 3 to 24 months after diagnosis. An iterative process was used to systematically analyze the data (the transcripts) using qualitative methods. Participants who worked during or after treatment adjusted their work schedule, performed fewer or other tasks, modified or changed their work environment, reduced non-work activities at the workplace, used cognitive prompts, and acted preemptively to make work tasks manageable after their return to work. Survivors used multiple adjustments and drew upon both formal and informal tactics to minimize or prevent cancer- or treatment-related effects from negatively affecting job performance. Knowledge about the broad range of both formal and informal strategies identified in this study may enable health care and social services providers, as well as cancer survivors and employers, to identify a wide range of specific strategies that may reduce the negative effects of work-related limitations in specific work settings. Insights gained from this analysis should inform future research on work and cancer survivorship. Copyright © 2014 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  5. Emerging treatment strategies in Tourette syndrome: what's in the pipeline?

    PubMed

    Termine, Cristiano; Selvini, Claudia; Rossi, Giorgio; Balottin, Umberto

    2013-01-01

    Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple motor/phonic tics and a wide spectrum of behavioral problems (e.g., complex tic-like symptoms, attention deficit hyperactivity disorder, and obsessive-compulsive disorder). TS can be a challenging condition even for the specialists, because of the complexity of the clinical picture and the potential adverse effects of the most commonly prescribed medications. Expert opinions and consensus guidelines on the assessment and treatment of tic disorders have recently been published in Europe and Canada. All pharmacological treatment options are mere symptomatic treatments that alleviate, but do not cure, the tics. We still lack evidence of their effects on the natural long-term course and on the prognosis of TS and how these treatments may influence the natural course of brain development. The most commonly prescribed drugs are dopamine antagonists, such as typical (e.g., haloperidol, pimozide) and atypical neuroleptics (e.g., risperidone, aripiprazole), and α-2-adrenoreceptor agonists (e.g., clonidine). However, several studies have investigated the efficacy and tolerability of alternative pharmacological agents that may be efficacious, including the newest atypical antipsychotic agents (e.g., paliperidone, sertindole), tetrabenazine, drugs that modulate acetylcholine (e.g., nicotine) and GABA (e.g., baclofen, levetiracetam), tetrahydrocannabinol, botulinum toxin injections, anticonvulsant drugs (e.g., topiramate, carbamazepine), naloxone, lithium, norepinephrine, steroid 5α reductase, and other neuroactive agents (buspirone, metoclopramide, phytostigmine, and spiradoline mesylate). As regards nonpharmacological interventions, some of the more recent treatments that have been studied include electroconvulsive therapy and repetitive transcranial magnetic stimulation. This review focuses primarily on the efficacy and safety of these emerging treatment strategies in TS.

  6. European Perspective on Multiple Myeloma Treatment Strategies in 2014

    PubMed Central

    Sonneveld, Pieter; Davies, Faith; Bladé, Joan; Boccadoro, Mario; Cavo, Michele; Morgan, Gareth; de la Rubia, Javier; Delforge, Michel; Dimopoulos, Meletios; Einsele, Hermann; Facon, Thierry; Goldschmidt, Hartmut; Moreau, Philippe; Nahi, Hareth; Plesner, Torben; San-Miguel, Jesús; Hajek, Roman; Sondergeld, Pia; Palumbo, Antonio

    2014-01-01

    The treatment of multiple myeloma has undergone significant changes and has resulted in the achievement of molecular remissions, the prolongation of remission duration, and extended survival becoming realistic goals, with a cure being possible in a small but growing number of patients. In addition, nowadays it is possible to categorize patients more precisely into different risk groups, thus allowing the evaluation of therapies in different settings and enabling a better comparison of results across trials. Here, we review the evidence from clinical studies, which forms the basis for our recommendations for the management of patients with myeloma. Treatment approaches depend on “fitness,” with chronological age still being an important discriminator for selecting therapy. In younger, fit patients, a short three drug-based induction treatment followed by autologous stem cell transplantation (ASCT) remains the preferred option. Consolidation and maintenance therapy are attractive strategies not yet approved by the European Medicines Agency, and a decision regarding post-ASCT therapy should only be made after detailed discussion of the pros and cons with the individual patient. Two- and three-drug combinations are recommended for patients not eligible for transplantation. Treatment should be administered for at least nine cycles, although different durations of initial therapy have only rarely been compared so far. Comorbidity and frailty should be thoroughly assessed in elderly patients, and treatment must be adapted to individual needs, carefully selecting appropriate drugs and doses. A substantial number of new drugs and novel drug classes in early clinical development have shown promising activity. Their introduction into clinical practice will most likely further improve treatment results. PMID:25063227

  7. Current and future systemic treatment options in metastatic pancreatic cancer

    PubMed Central

    Arslan, Cagatay

    2014-01-01

    Although pancreatic adenocarcinoma is the fourth leading cause of cancer death, only modest improvement has been observed in the past two decades, single agent gemcitabine has been the only standard treatment in patients with advanced disease. Recently newer agents such as nab-paclitaxel, nimotuzumab and regimens such as FOLFIRINOX have been shown to have promising activity being superior to gemcitabine as a single agent. With better understanding of tumour biology coupled with the improvements in targeted and immunotherapies, there is increasing expectation for better response rates and extended survival in pancreatic cancer. PMID:25083302

  8. Multistrain models predict sequential multidrug treatment strategies to result in less antimicrobial resistance than combination treatment.

    PubMed

    Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo; Græsbøll, Kaare; Toft, Nils; Matthews, Louise; Olsen, John Elmerdahl; Nielsen, Søren Saxmose

    2016-06-23

    Combination treatment is increasingly used to fight infections caused by bacteria resistant to two or more antimicrobials. While multiple studies have evaluated treatment strategies to minimize the emergence of resistant strains for single antimicrobial treatment, fewer studies have considered combination treatments. The current study modeled bacterial growth in the intestine of pigs after intramuscular combination treatment (i.e. using two antibiotics simultaneously) and sequential treatments (i.e. alternating between two antibiotics) in order to identify the factors that favor the sensitive fraction of the commensal flora. Growth parameters for competing bacterial strains were estimated from the combined in vitro pharmacodynamic effect of two antimicrobials using the relationship between concentration and net bacterial growth rate. Predictions of in vivo bacterial growth were generated by a mathematical model of the competitive growth of multiple strains of Escherichia coli. Simulation studies showed that sequential use of tetracycline and ampicillin reduced the level of double resistance, when compared to the combination treatment. The effect of the cycling frequency (how frequently antibiotics are alternated in a sequential treatment) of the two drugs was dependent upon the order in which the two drugs were used. Sequential treatment was more effective in preventing the growth of resistant strains when compared to the combination treatment. The cycling frequency did not play a role in suppressing the growth of resistant strains, but the specific order of the two antimicrobials did. Predictions made from the study could be used to redesign multidrug treatment strategies not only for intramuscular treatment in pigs, but also for other dosing routes.

  9. Endoscopic treatments for obesity: past, present and future.

    PubMed

    Gostout, Christopher J; Rajan, Elizabeth

    2005-03-01

    Obesity is recognized as a serious, chronic illness affecting all ages. The cause for obesity is multi-factorial, which makes successful management complex and challenging. Meaningful weight loss is frequently difficult to achieve, particularly when the goal is not merely to lose weight but to maintain this loss. The efficacy of future endoscopic approaches needs to be validated through well-designed controlled studies, and verification of safety is essential. Endoluminal therapies must have a sound physiologic basis for their development. The availability of specialized radionuclide imaging of gastric capacity and accommodation provide a useful tool in constructing interventions. Endotherapy is likely best suited for nonmorbid obese individuals with BMI ranging from 30 to 39 or as a budge to bariatric surgery. This specific BMI range has been targeted by the National Institutes of Health for emerging technologies. Presurgical weight loss to reduce surgical risk is another potential target group. Regardless of which endoscopic methods prevail, patients will continue to require a comprehensive, multi-modality management approach to this complex disease.

  10. Targeted treatment of pruritus - a look into the future

    PubMed Central

    Tey, H.L.; Yosipovitch, G

    2011-01-01

    Recent advances in pruritus research have elucidated mediators and neuronal pathways involved in itch transmission and this fast-emerging knowledge may possibly be translated into new therapies in the near future. In the skin and peripheral nerves, potential mediator and receptor therapeutic targets include the H4 histamine receptor, proteinase-activated receptor 2, serine proteases, Cathepsin S, peripheral mu- and kappa-opioid receptors, interleukin-31, transient receptor potential vanilloid 1 and 3, fatty acid amide hydrolase, nerve growth factor and its receptor, acetylcholine, and the Mas-related G-protein-coupled receptor. In the spinal cord, gastrin-related peptide and its receptor, as well as substance P and its receptor neurokinin receptor-1 serve as potential therapeutic targets. In the brain, reduction of itch perception and modulation of emotions may possibly be achieved through drugs acting on the anterior cingulate cortex. Clinically, management of pruritus should be instituted early and address the skin pathology, peripheral neuropathy, central sensitisation, and the cognito-affective aspects of the disease. PMID:21219293

  11. Future tendencies of climate indicators important for adaptation and mitigation strategies in forestry

    NASA Astrophysics Data System (ADS)

    Galos, Borbala; Hänsler, Andreas; Gulyas, Krisztina; Bidlo, Andras; Czimber, Kornel

    2014-05-01

    impact analyses and build an important basis of the future adaptation strategies in forestry, agriculture and water management. Funding: The research is supported by the TÁMOP-4.2.2.A-11/1/KONV-2012-0013 and TÁMOP-4.1.1.C-12/1/KONV-2012-0012 (ZENFE) joint EU-national research projects. Keywords: climate indices, climate change impacts, forestry, regional climate modelling

  12. Future therapeutic treatment of COPD: Struggle between oxidants and cytokines

    PubMed Central

    de Boer, Willem I; Yao, Hongwei; Rahman, Irfan

    2007-01-01

    Chronic obstructive pulmonary disease (COPD) is a global health problem. Being a progressive disease characterized by inflammation and predominantly caused by tobacco smoking, it deteriorates pulmonary and skeletal muscle functioning, and reduces physical behavior, societal participation and quality of life. During the last two decades studies were focused on the airway and systemic inflammation, oxidative stress, and airway and/or parenchymal remodeling. Macrophages, neutrophils and T cells are thought to be important key players, as well as structural cells like fibroblasts, epithelial, endothelial and smooth muscle cells. Mediators and proteins including cytokines, chemokines, growth factors, proteinases, and oxidants seem to be involved differentially in its pathogenesis. Current pharmacological treatments are directed to reducing airway inflammation, boosting the endogenous levels of anti-oxidants and relieving airway contraction and sputum production. Most agents were primarily used for treating asthma. But in contrast to asthma, these treatments are not very effective in COPD. As a result, novel more specifically acting interventional drugs with less side effects are being developed to treat chronic inflammatory diseases, including COPD. This review highlights studies on novel or potential drug antioxidants such as dietary antioxidants supplementation, N-acetyl-L-cysteine, N-acystelyn, endosteine, antioxidant enzyme mimetics, and anti-inflammatory agents like antagonists of cytokines, such as tumor necrosis factor (TNF)-α, CXCL8, and CCL2, and inhibitors of signal transduction proteins including phosphodiesterase 4, MAPK p38, Pl-3k, and NFκB. PMID:18229560

  13. Life After the George W. Bush Administration: A New US Strategy Towards China for Future Administrations

    DTIC Science & Technology

    2008-05-15

    grand strategy is required. Contemporary International Relations Theories Literary Nobel Prize winner Bertrand Russell wrote, “Love of power, like...strategy, a comprehensive look at current international relations theories and how these theories help provide a framework for grand strategy is...recommended strategy towards China. To provide a recommended strategy, a comprehensive look at current international relations theories and how these

  14. Descending thoracic aortic mural thrombus presentation and treatment strategies.

    PubMed

    Meyermann, Karol; Trani, Jose; Caputo, Francis J; Lombardi, Joseph V

    2017-09-01

    Thoracic aortic mural thrombus (TAMT) of the descending aorta is rare but can result in dramatic embolic events. Early treatment is therefore crucial; however, there is not a consensus on ideal initial treatment. A review of the literature using PubMed was conducted, and all relevant publications describing descending TAMT of the past 15 years were reviewed. Variables included for this analysis were presentation, initial treatment strategy employed, outcome measures of thrombus resolution or regression, recurrence of symptomatic emboli, and mortality. Seventy-four patients were included in this analysis. Women were significantly more likely to be described with descending TAMT. The majority (82.4%) of cases reported were diagnosed after an embolic event. Patients were equally likely to receive medical, open surgical, or endovascular therapy as the initial treatment modality. However, there is a trend within the past 5 years to report cases describing successful thoracic endovascular aortic repair for initial management. Of patients who initially underwent medical management, nine patients (34.6%) had persistent thrombus. Of the patients who initially underwent open surgical repair, six patients (31.6%) had persistent thrombus; of these patients, four underwent endovascular repair. Twenty-nine patients (39.2%) with descending TAMT initially underwent thoracic endovascular aortic repair. Twenty-seven (93.1%) had fully excluded thrombus at the time of the procedure, with no recurrence or evidence of repeated embolic phenomena at follow-up. Whereas mural thrombus of the thoracic aorta is uncommon, it must be considered in the differential diagnosis of embolic events. Although endovascular therapy may be a useful first-line option for TAMT with reports of positive outcomes in select literature, further study of this treatment option is required. Copyright © 2017. Published by Elsevier Inc.

  15. [Future methods of treatment in age related macular degeneration].

    PubMed

    Turlea, C

    2012-01-01

    In the present time the treatment of Age Related Macular Degeneration (ARMD) begins to develop. Many medical therapies are presently tested in the two types of ARMD, geographic atrophy and exudative ARMD. In atrophic ARMD, new drugs are aimed to spare photoreceptors and the retinal pigment epithelium, to prevent oxidative damage on the retina and to suppress the inflammation process. In exudative ARMD, new therapies are already in use and in progress, especially the anti-VEGF factors, and others try to improve visual prognosis in targeting other mechanism or cells involved in the angiogenesis process. This article reviews and summarizes the available data, presented in several scientific meetings, congresses or given directly by the companies involved.

  16. Treatment paradigms for cataplexy in narcolepsy: past, present, and future

    PubMed Central

    Swick, Todd J

    2015-01-01

    Cataplexy is defined as episodes of sudden loss of voluntary muscle tone triggered by emotions generally lasting <2 minutes. Cataplexy is most commonly associated with and considered pathognomonic for narcolepsy, a sleep disorder affecting ~0.05% of the general population. Knowledge of the pathophysiology of cataplexy has advanced through study of canine, murine, and human models. It is now generally considered that loss of signaling by hypothalamic hypocretin/orexin-producing neurons plays a key role in the development of cataplexy. Although the cause of hypocretin/orexin neuron loss in narcolepsy with cataplexy is unknown, an autoimmune etiology is widely hypothesized. Despite these advances, a literature review shows that treatment of cataplexy remains limited. Multiple classes of antidepressants have been commonly used off-label for cataplexy in narcolepsy and are suggested for this use in expert consensus guidelines based on traditional practice, case reports, and small trials. However, systematic research evidence supporting antidepressants for cataplexy is lacking. The single pharmacotherapy indicated for cataplexy and the guideline-recommended first-line treatment in Europe and the US is sodium oxybate, the sodium salt of gamma-hydroxybutyrate. Clinical trial evidence of its efficacy and safety in cataplexy is robust, and it is hypothesized that its therapeutic effects may occur through gamma-aminobutyric acid receptor type B-mediated effects at noradrenergic, dopaminergic, and thalamocortical neurons. Additional possible mechanisms for cataplexy therapy suggested by preliminary research include antagonism of the histamine H3 autoreceptor with pitolisant and intravenous immunoglobulin therapy for amelioration of the presumed autoimmune-mediated hypocretin/orexin cell loss. Further research and development of therapeutic approaches to cataplexy are needed. PMID:26715865

  17. Treatment paradigms for cataplexy in narcolepsy: past, present, and future.

    PubMed

    Swick, Todd J

    2015-01-01

    Cataplexy is defined as episodes of sudden loss of voluntary muscle tone triggered by emotions generally lasting <2 minutes. Cataplexy is most commonly associated with and considered pathognomonic for narcolepsy, a sleep disorder affecting ~0.05% of the general population. Knowledge of the pathophysiology of cataplexy has advanced through study of canine, murine, and human models. It is now generally considered that loss of signaling by hypothalamic hypocretin/orexin-producing neurons plays a key role in the development of cataplexy. Although the cause of hypocretin/orexin neuron loss in narcolepsy with cataplexy is unknown, an autoimmune etiology is widely hypothesized. Despite these advances, a literature review shows that treatment of cataplexy remains limited. Multiple classes of antidepressants have been commonly used off-label for cataplexy in narcolepsy and are suggested for this use in expert consensus guidelines based on traditional practice, case reports, and small trials. However, systematic research evidence supporting antidepressants for cataplexy is lacking. The single pharmacotherapy indicated for cataplexy and the guideline-recommended first-line treatment in Europe and the US is sodium oxybate, the sodium salt of gamma-hydroxybutyrate. Clinical trial evidence of its efficacy and safety in cataplexy is robust, and it is hypothesized that its therapeutic effects may occur through gamma-aminobutyric acid receptor type B-mediated effects at noradrenergic, dopaminergic, and thalamocortical neurons. Additional possible mechanisms for cataplexy therapy suggested by preliminary research include antagonism of the histamine H3 autoreceptor with pitolisant and intravenous immunoglobulin therapy for amelioration of the presumed autoimmune-mediated hypocretin/orexin cell loss. Further research and development of therapeutic approaches to cataplexy are needed.

  18. Pediatric gastroesophageal varices: treatment strategy and long-term results.

    PubMed

    Mitsunaga, Tetsuya; Yoshida, Hideo; Kouchi, Katsunori; Hishiki, Tomoro; Saito, Takeshi; Yamada, Shin-ichi; Sato, Yoshiharu; Terui, Keita; Nakata, Mitsuyuki; Takenouchi, Ayako; Ohnuma, Naomi

    2006-12-01

    There are various treatment strategies for gastroesophageal varices in children. We studied the therapeutic value of endoscopic variceal clipping (EVC) and ligation (EVL). Four hundred ninety-nine endoscopic examinations performed between 1991 and 2005 were retrospectively analyzed. F2 and F3 varices with red color signs on follow-up endoscopy were treated with prophylactic EVC. In variceal rupture cases, EVC and EVL were used in combination. Eighty-two prophylactic EVCs were done, and variceal progression was prevented in 89.9%. However, some patients had persistent red color signs and required frequent EVC. Ten emergent procedures were done for variceal rupture, and, in 4 cases, EVL was used to arrest massive variceal bleeding. Five patients developed bleeding during follow-up cause by rupture of gastric fundal varices, which probably had been aggravated by prior treatment for esophageal varices. The control of gastroesophageal varices by routine EVC was satisfactory. However, ruptures during follow-up suggested the importance of controlling gastric fundal varices. Endoscopic variceal ligation is a simple, effective, and safe treatment tool, particularly for ruptured varices. However, it is difficult to treat gastric fundal varices with EVL; this disadvantage of EVL can be overcome by the concomitant use of EVC.

  19. Bone marrow concentrate: a novel strategy for bone defect treatment.

    PubMed

    Jäger, Marcus; Jelinek, Eva M; Wess, Kai M; Scharfstädt, Axel; Jacobson, May; Kevy, Sherwin V; Krauspe, Rüdiger

    2009-01-01

    Although strong efforts have been made over the last decade to introduce stem cell and tissue engineering treatment strategies to the field of orthopaedics, only few clinical applications are currently available. The clinical outcomes of ten patients with volumetric bone deficiencies treated with mesenchymal stem cells and bone marrow aspirate are presented in this case series. Results were evaluated with radiographs. In addition to the in vivo data, we also presented in vitro data of BMC cultivated onto a porous collagen I scaffold and the technique of bone marrow aspiration via a commercially available system. Our results demonstrated that there is a rationale for a clinical application of BMC / bone aspirate in the treatment of osseous defects. The intraoperative harvest procedure is a safe method and does not significantly prolong the time of surgery. In addition, MSC isolated from the aspirate was able to adhere and proliferate onto a collagen scaffold in significant numbers after a 15 min incubation period. These cells were then able to allow osteogenic differentiation in vitro without any osteogenic stimuli. The local application of BMC / bone aspirate in the treatment of bone deficiencies may be a promising alternative to autogenous bone grafting and help reduce donor site morbidity.

  20. Recommendations for severe hypertriglyceridemia treatment, are there new strategies?

    PubMed

    Filippatos, Theodosios D; Elisaf, Moses S

    2014-01-01

    This review considers drug combinations and newer treatment strategies for patients with severe hypertriglyceridemia. Hypertriglyceridemia is associated with an atherogenic metabolic profile and in most studies with increased cardiovascular disease risk. Patients with severe hypertriglyceridemia also have increased incidence of pancreatitis. All types of severe hypertriglyceridemia are associated with a reduction in lipoprotein lipase activity. Patients with severe hypertriglyceridemia and abdominal pain or pancreatitis should be hospitalized and treated with hypolipidemic drugs and, if needed, with insulin/dextrose infusion or therapeutic apheresis. Fibrates are the first-line treatment in patients with severe hypertriglyceridemia. Omega-3 fatty acids and niacin are very useful drugs for patients with hypertriglyceridemia. Statins in high doses exhibit a significant hypotriglyceridemic activity. Drugs that interfere with chylomicron production such as orlistat are also useful for hypertriglyceridemic patients. In most patients with severe hypertriglyceridemia drug combinations are needed to maintain an acceptable triglyceride concentration. Gene therapy is under development for patients with known genetic abnormalities of triglyceride metabolism. Clinicians should be vigilant for the recognition and prompt treatment of patients with severe hypertriglyceridemia aimed to avoid the serious complication of pancreatitis and to reduce their cardiovascular risk.

  1. Thrombolysis in acute myocardial infarction: need for a change in strategy and future directions.

    PubMed

    Pitt, B

    1990-01-01

    The results of several major trials of i.v. thrombolysis in patients with acute myocardial infarction have demonstrated the efficacy of the treatment in reducing mortality. Streptokinase and rt-PA have been shown to be effective (APSAC = anisoylated plasminogen streptokinase activator complex; GISSI = Gruppo Italiano per lo Studio della Streptochinasi nell' Infarto miocardico, ASSET = Anglo Scandinavian study of early thrombolysis, rt-PA). This treatment is associated with the potential for cerebral and major bleeding, especially in elderly patients. The benefit of this treatment in patients with cardiogenic shock or hypotension (ISIS-2) is discussed. There is no convincing evidence that patients with ST-segment depression or those with an equivocal electrocardiogram had been benefited from i.v. thrombolysis. Further studies with i.v. thrombolysis and/or other strategies need to be explored. Overall the use of i.v. thrombolytic agents in combination with PTCA in patients with acute myocardial infarction have resulted in improvement in ventricular function and survival in patients eligible for this therapy. However, new techniques and therapeutic approaches to prevent reocclusion, to prevent reperfusion injury, to prevent restenosis after PTCA, to prevent atherosclerosis in the infarct and non-infarct related arteries, and to reduce the potential for ventricular arrhythmias and sudden death as well as the potential for mural thrombi and embolization after infarction are needed. The 1990's will see attempts to determine the optimum adjunctive therapy or "cocktail" of agents to be used with i.v. thrombolysis.

  2. 17 CFR 1.30 - Loans by futures commission merchants; treatment of proceeds.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Loans by futures commission merchants; treatment of proceeds. 1.30 Section 1.30 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION GENERAL REGULATIONS UNDER THE COMMODITY EXCHANGE ACT Customers' Money, Securities, and...

  3. Developing America's Shale Reserves - Water Strategies For A Sustainable Future (Invited)

    NASA Astrophysics Data System (ADS)

    Shephard, L. E.; Oshikanlu, T.

    2013-12-01

    The development of shale oil and gas reserves over the last several years has had a significant impact on securing America's energy future while making substantial contributions to our nation's economic prosperity. These developments have also raised serious concerns about potential detrimental impacts to our environment (i.e., land, air and water) with much media attention focused on the impacts to our nation's fresh water supply. These concerns are being discussed across the nation often with little or no distinction that the nature of the water issues vary depending on local circumstances (e.g., depth of aquifer and reservoir zone, water demand and availability, availability of discharge wells, regulatory framework, etc.) and regional shale reservoir development strategies (depth of wells, length of laterals, fluid-type used for fracturing, etc.). Growing concerns over long standing drought conditions in some areas and competing demands for water from other sectors (e.g., agriculture, domestic, etc.) add even greater uncertainty relative to fresh water. Water demands for gas and oil wells vary from region to region but nominally range from 10 to 15 acre feet of water (4 to 6 million gallons) for drilling and hydraulic fracturing applications. Flowback water from the hydraulic fracturing process varies and can range from 5 to 40 % of the water used for drilling and 'fracing'. Produced water can be substantial, leading to significant volumes of 'disposed water' where injection wells are available. A science-based systems approach to water lifecycle management that incorporates leading-edge technology development and considers economic and social impacts is critical for the long-term sustainable development of shale reserves. Various water recycling and reuse technologies are being deployed within select regions across the nation with each having limited success depending on region. The efficacy of reuse technology will vary based on produced water quantity and

  4. Gene delivery strategies for the treatment of mucopolysaccharidoses.

    PubMed

    Baldo, Guilherme; Giugliani, Roberto; Matte, Ursula

    2014-03-01

    Mucopolysaccharidosis (MPS) disorders are genetic diseases caused by deficiencies in the lysosomal enzymes responsible for the degradation of glycosaminoglycans. Current treatments are not able to correct all disease symptoms and are not available for all MPS types, which makes gene therapy especially relevant. Multiple gene therapy approaches have been tested for different types of MPS, and our aim in this study is to critically analyze each of them. In this review, we have included the major studies that describe the use of adeno-associated retroviral and lentiviral vectors, as well as relevant non-viral approaches for MPS disorders. Some protocols such as the use of adeno-associated vectors and lentiviral vectors are approaching the clinic for these disorders and, along with combined approaches, seem to be the future of gene therapy for MPS.

  5. Strategies for Reforestation under Uncertain Future Climates: Guidelines for Alberta, Canada

    PubMed Central

    Gray, Laura K.; Hamann, Andreas

    2011-01-01

    Background Commercial forestry programs normally use locally collected seed for reforestation under the assumption that tree populations are optimally adapted to local environments. However, in western Canada this assumption is no longer valid because of climate trends that have occurred over the last several decades. The objective of this study is to show how we can arrive at reforestation recommendations with alternative species and genotypes that are viable under a majority of climate change scenarios. Methodology/Principal Findings In a case study for commercially important tree species of Alberta, we use an ecosystem-based bioclimate envelope modeling approach for western North America to project habitat for locally adapted populations of tree species using multi-model climate projections for the 2020s, 2050s and 2080s. We find that genotypes of species that are adapted to drier climatic conditions will be the preferred planting stock over much of the boreal forest that is commercially managed. Interestingly, no alternative species that are currently not present in Alberta can be recommended with any confidence. Finally, we observe large uncertainties in projections of suitable habitat that make reforestation planning beyond the 2050s difficult for most species. Conclusion/Significance More than 50,000 hectares of forests are commercially planted every year in Alberta. Choosing alternative planting stock, suitable for expected future climates, could therefore offer an effective climate change adaptation strategy at little additional cost. Habitat projections for locally adapted tree populations under observed climate change conform well to projections for the 2020s, which suggests that it is a safe strategy to change current reforestation practices and adapt to new climatic realities through assisted migration prescriptions. PMID:21853061

  6. Strategies for reforestation under uncertain future climates: guidelines for Alberta, Canada.

    PubMed

    Gray, Laura K; Hamann, Andreas

    2011-01-01

    Commercial forestry programs normally use locally collected seed for reforestation under the assumption that tree populations are optimally adapted to local environments. However, in western Canada this assumption is no longer valid because of climate trends that have occurred over the last several decades. The objective of this study is to show how we can arrive at reforestation recommendations with alternative species and genotypes that are viable under a majority of climate change scenarios. In a case study for commercially important tree species of Alberta, we use an ecosystem-based bioclimate envelope modeling approach for western North America to project habitat for locally adapted populations of tree species using multi-model climate projections for the 2020s, 2050s and 2080s. We find that genotypes of species that are adapted to drier climatic conditions will be the preferred planting stock over much of the boreal forest that is commercially managed. Interestingly, no alternative species that are currently not present in Alberta can be recommended with any confidence. Finally, we observe large uncertainties in projections of suitable habitat that make reforestation planning beyond the 2050s difficult for most species. More than 50,000 hectares of forests are commercially planted every year in Alberta. Choosing alternative planting stock, suitable for expected future climates, could therefore offer an effective climate change adaptation strategy at little additional cost. Habitat projections for locally adapted tree populations under observed climate change conform well to projections for the 2020s, which suggests that it is a safe strategy to change current reforestation practices and adapt to new climatic realities through assisted migration prescriptions.

  7. Alcoholic neuropathy: possible mechanisms and future treatment possibilities

    PubMed Central

    Chopra, Kanwaljit; Tiwari, Vinod

    2012-01-01

    Chronic alcohol consumption produces painful peripheral neuropathy for which there is no reliable successful therapy, mainly due to lack of understanding of its pathobiology. Alcoholic neuropathy involves coasting caused by damage to nerves that results from long term excessive drinking of alcohol and is characterized by spontaneous burning pain, hyperalgesia and allodynia. The mechanism behind alcoholic neuropathy is not well understood, but several explanations have been proposed. These include activation of spinal cord microglia after chronic alcohol consumption, oxidative stress leading to free radical damage to nerves, activation of mGlu5 receptors in the spinal cord and activation of the sympathoadrenal and hypothalamo-pituitary-adrenal (HPA) axis. Nutritional deficiency (especially thiamine deficiency) and/or the direct toxic effect of alcohol or both have also been implicated in alcohol-induced neuropathic pain. Treatment is directed towards halting further damage to the peripheral nerves and restoring their normal functioning. This can be achieved by alcohol abstinence and a nutritionally balanced diet supplemented by all B vitamins. However, in the setting of ongoing alcohol use, vitamin supplementation alone has not been convincingly shown to be sufficient for improvement in most patients. The present review is focused around the multiple pathways involved in the development of peripheral neuropathy associated with chronic alcohol intake and the different therapeutic agents which may find a place in the therapeutic armamentarium for both prevention and management of alcoholic neuropathy. PMID:21988193

  8. Treatment of hereditary epidermolysis bullosa: updates and future prospects.

    PubMed

    Hsu, Chao-Kai; Wang, Sheng-Pei; Lee, Julia Yu-Yun; McGrath, John A

    2014-02-01

    Epidermolysis bullosa (EB) represents a group of inherited blistering skin diseases, some forms of which are associated with considerable morbidity and increased mortality. Notably, in recessive dystrophic EB there can be extensive muco-cutaneous fragility and disease complications such as scars, contractures, anemia, malnutrition, and malignancy. Currently, there is no effective therapy or cure for EB. Over the last decade, however, a number of important advances have been made that are bringing new treatments closer to the clinic, including gene therapy, protein replacement therapy, cell therapies [allogeneic fibroblasts, mesenchymal stromal cells (MSCs), bone marrow stem cell transplantation, culturing/grafting revertant mosaic keratinocytes], gene editing/engineering, and clinical application of inducible pluripotent stem cells. Although a cure for EB still remains elusive, recent data on animal models and initial human clinical trials have raised the expectations of patients, clinicians, and researchers that disease modification and improved quality of life are feasible goals. Furthermore, the lessons learned in treating EB are likely to have significant implications for improving the management of other genetic diseases.

  9. Are bio-absorbable stents the future of SFA treatment?

    PubMed

    Peeters, P; Keirse, K; Verbist, J; Deloose, K; Bosiers, M

    2010-02-01

    Several limitations inherent to the implantation of a metallic device, such as the occurrence of in-stent re-stenosis, in an arterial lumen intuitively explain the interest for developing bio-absorbable stents. Two main types of bio-absorbable stents currently exist: polymer stents and metallic stents. To date, no studies with bio-absorbable stents have been conducted in the superficial femoral artery (SFA). Because of their strut thickness and lack of radial force, polymer stents are no good candidates for endovascular use. Absorbable metal stents (AMS) do have the potential to perform well for artery treatment, although current evidence from in-human coronary and infrapopliteal studies yield unsatisfactory results. Drastic technological improvements are mandatory before AMS can be considered for every day practice. Yet, it is our belief that further development of other metal and non-metal bio-absorbable stents, with or without drug-coating, may lead to the creation of the ultimate SFA stent.

  10. Treatment of Nonalcoholic Steatohepatitis in Adults: Present and Future

    PubMed Central

    Gitto, S.; Vitale, G.; Villa, E.; Andreone, P.

    2015-01-01

    Nonalcoholic steatohepatitis has become one of the most common liver-related health problems. This condition has been linked to an unhealthy diet and weight gain, but it can also be observed in nonobese people. The standard of care is represented by the lifestyle intervention. However, because this approach has several limitations, such as a lack of compliance, the use of many drugs has been proposed. The first-line pharmacological choices are vitamin E and pioglitazone, both showing a positive effect on transaminases, fat accumulation, and inflammation. Nevertheless, vitamin E has no proven effect on fibrosis and on long-term morbidity and mortality and pioglitazone has a negative impact on weight. Other drugs have been studied such as metformin, ursodeoxycholic acid, statins, pentoxiphylline, and orlistat with only partially positive results. Among the emerging treatments, telmisartan is particularly interesting as it seems to have an impact on insulin resistance, liver steatosis, inflammation, and fibrosis. However, the pathogenesis of steatohepatitis is highly complex and is determined by different parallel hits; indeed, the association of different drugs that act on various levels has been suggested. In conclusion, lifestyle intervention should be optimised and the associations of different drugs should be tested in large studies with long-term outcomes. PMID:25866507

  11. Treatment of Rapidly Progressive Systemic Sclerosis: Current and Futures Perspectives

    PubMed Central

    Mendoza, Fabian A.; Mansoor, Maryah; Jimenez, Sergio A.

    2016-01-01

    Introduction Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by severe and often progressive cutaneous, pulmonary, cardiac and gastrointestinal tract fibrosis, cellular and humoral immunologic alterations, and pronounced fibroproliferative vasculopathy. There is no effective SSc disease modifying therapy. Patients with rapidly progressive SSc have poor prognosis with frequent disability and very high mortality. Areas Covered This paper reviews currently available therapeutic approaches for rapidly progressive SSc and discuss novel drugs under study for SSc disease modification. Expert Opinion The extent, severity, and rate of progression of SSc skin and internal organ involvement determines the optimal therapeutic interventions for SSc. Cyclophosphamide for progressive SSc-associated interstitial lung disease and mycophenolate for rapidly progressive cutaneous involvement have shown effectiveness. Methotrexate has been used for less severe skin progression and for patients unable to tolerate mycophenolate. Rituximab was shown to induce improvement in SSc-cutaneous and lung involvement. Autologous bone marrow transplantation is reserved for selected cases in whom poor survival risk outweighs the high mortality rate of the procedure. Novel agents capable of modulating fibrotic and inflammatory pathways involved in SSc pathogenesis, including tocilizumab, pirfenidone, tyrosine kinase inhibitors, lipid lysophosphatidic acid 1, and NOX4 inhibitors are currently under development for the treatment of rapidly progressive SSc. PMID:27812432

  12. Comparison of treatment strategies for space motion sickness

    NASA Technical Reports Server (NTRS)

    Davis, J. R.; Jennings, R. T.; Beck, B. G.

    1991-01-01

    Treatment strategies for space motion sickness were compared using the results of postflight oral debriefings. Standardized questionnaires were administered to all crewmembers immediately following Space Shuttle flights by NASA flight surgeons. Cases of space motion sickness were graded as mild, moderate, or severe based on published criteria, and medication effectiveness was judged based on subjective reports of symptom relief. Since October 1989, medication effectiveness is reported inflight through private medical conferences with the crew. A symptom matrix was analyzed for nineteen crewmembers treated with an oral combination of scopolomine and dextroamphetamine (scopdex) and fifteen crewmembers treated with promethazine delivered by intramuscular or suppository routes. Scopdex has been given preflight as prophylaxis for space motion sickness but analysis showed delayed symptom presentation in nine crewmembers or failed to prevent symptoms in seven.

  13. Comparison of treatment strategies for space motion sickness

    NASA Technical Reports Server (NTRS)

    Davis, J. R.; Jennings, R. T.; Beck, B. G.

    1991-01-01

    Treatment strategies for space motion sickness were compared using the results of postflight oral debriefings. Standardized questionnaires were administered to all crewmembers immediately following Space Shuttle flights by NASA flight surgeons. Cases of space motion sickness were graded as mild, moderate, or severe based on published criteria, and medication effectiveness was judged based on subjective reports of symptom relief. Since October 1989, medication effectiveness is reported inflight through private medical conferences with the crew. A symptom matrix was analyzed for nineteen crewmembers treated with an oral combination of scopolomine and dextroamphetamine (scopdex) and fifteen crewmembers treated with promethazine delivered by intramuscular or suppository routes. Scopdex has been given preflight as prophylaxis for space motion sickness but analysis showed delayed symptom presentation in nine crewmembers or failed to prevent symptoms in seven.

  14. A mathematical model to guide antibiotic treatment strategies.

    PubMed

    Sotto, Albert; Lavigne, Jean-Philippe

    2012-08-13

    Over the past few decades, the emergence of multidrug resistance (MDR) to antibiotics in bacteria has led to major difficulties in the management of infected patients. At present, there is a serious lack of development of new antibacterial agents. Mathematical models are one approach to understand how antibiotic usage patterns may be optimized. However, the classical approach to modeling the emergence of MDR relies on the simplifying assumption that resistance is acquired at a constant rate. In their model, Obolski and Hadany introduce the notion of horizontal gene transfer and stress-induced mutation, with antibiotics constituting an environmental stressor of particular relevance. Finally, from this complex mathematical model, the authors propose predictions for minimizing MDR in bacteria depending on strategies of antibiotic treatment. Please see related article: http://www.biomedcentral.com/1741-7015/10/89.

  15. Biomaterial Design Strategies for the Treatment of Spinal Cord Injuries

    PubMed Central

    Straley, Karin S.; Po Foo, Cheryl Wong

    2010-01-01

    Abstract The highly debilitating nature of spinal cord injuries has provided much inspiration for the design of novel biomaterials that can stimulate cellular regeneration and functional recovery. Many experts agree that the greatest hope for treatment of spinal cord injuries will involve a combinatorial approach that integrates biomaterial scaffolds, cell transplantation, and molecule delivery. This manuscript presents a comprehensive review of biomaterial-scaffold design strategies currently being applied to the development of nerve guidance channels and hydrogels that more effectively stimulate spinal cord tissue regeneration. To enhance the regenerative capacity of these two scaffold types, researchers are focusing on optimizing the mechanical properties, cell-adhesivity, biodegradability, electrical activity, and topography of synthetic and natural materials, and are developing mechanisms to use these scaffolds to deliver cells and biomolecules. Developing scaffolds that address several of these key design parameters will lead to more successful therapies for the regeneration of spinal cord tissue. PMID:19698073

  16. Immunotherapy: New Strategies for the Treatment of Gynecologic Malignancies

    PubMed Central

    Bourla, Ariel Bulua; Zamarin, Dmitriy

    2016-01-01

    Over the past decade, the ability of cancer cells to evade immune destruction has become recognized as one of the hallmarks of cancer. This understanding has paved the way for the development of novel therapeutic agents that can enhance activation of antitumor immune responses or reverse immunosuppressive mechanisms through which tumors escape immune-mediated rejection. The treatment of gynecologic cancers remains a therapeutic challenge, as these malignancies are often diagnosed in advanced stages, and many patients relapse despite appropriate management. Clinical trials have shown efficacy for various immunotherapeutic strategies, especially the use of tumor-targeting antibodies; enhancement of tumor antigen presentation, such as with vaccines and toll-like receptor agonists; and agents targeting immunosuppressive mechanisms, such as checkpoint blockade inhibitors. Emerging data on new and combination approaches currently under investigation provide a strong rationale for these approaches. PMID:26791846

  17. [Evaluation of treatment strategies in obstetrics and gynaecology].

    PubMed

    Mol, Ben Willem

    2013-01-01

    Randomised clinical trials are the preferred tool to assess the effectiveness of new treatment strategies and to compare the effectiveness of existing techniques. Since it is virtually impossible to complete studies with the required sample sizes in a single centre or even a few centres, from 2003 onwards 70 Dutch hospitals have since joined forces in the initiation and execution of large clinical studies. The consortia address pragmatic questions in the fields of obstetrics, gynaecology and reproductive medicine. The construction of a common infrastructure for ethical approval, recruitment of patients, data management and analysis is central to this collaboration. Research nurses and midwives play a key role in the recruitment of participants and the collection of data. In this article we consider if in view of the results obtained, funding from government and insurance companies and the participation of health care providers can continue to be as liberal as it has been up to now.

  18. Shift work disorder: clinical assessment and treatment strategies.

    PubMed

    Simon, Richard D

    2012-06-01

    Shift work disorder (SWD) occurs when individuals are unable to successfully synchronize their internal clocks with a work schedule that requires them to stay awake when it is dark and sleep when it is light. When assessing for SWD, clinicians should take a thorough sleep history and have the patient maintain a sleep diary. Clinicians should also be aware of conditions that commonly occur in conjunction with this illness, including sleep apnea, restless legs syndrome, depressive and anxiety disorders, and chronic fatigue. The primary goal of treatment for SWD is to reduce the rate of circadian misalignment by fostering better sleep when it is desired and improved alertness and functioning when appropriate. Nonpharmacologic strategies (eg, melatonin and light therapy) should be tried before considering medications to promote sleep and/or alertness. © Copyright 2012 Physicians Postgraduate Press, Inc.

  19. Treatment strategies in myocardial bridging: a case report.

    PubMed

    Dursun, Ihsan; Bahcivan, Muzaffer; Durna, Kenan; Ibrahimov, Firdovsi; Erk, Noker Han; Yasar, Erdogan; Sahin, Mahmut

    2006-01-01

    Myocardial bridging is one of the nonatherosclerotic causes of coronary artery disease and is characterized by muscles overlying the intramyocardial course of a major epicardial coronary artery segment, leading to systolic compression. Myocardial bridging is considered a benign condition in most cases, but has been associated with serious cardiac events such as myocardial infarction and sudden death. We discuss the case of a 63-year-old man who was admitted to our hospital with effort-induced angina, bradycardia, and left ventricular hypertrophy on electrocardiogram. On coronary angiography, we found significant myocardial bridging with total occlusion in the left anterior descending artery during systole. In patients with myocardial bridging, symptoms often manifest during exercise and with tachycardia. But it is interesting to note that our patient was bradycardic and became symptomatic with minimal effort. Thus, we thought that these emphasized its significance and affected treatment strategy.

  20. Introduction to Dynamic Treatment Strategies and Sequential Multiple Assignment Randomization

    PubMed Central

    Lavori, Philip W.; Dawson, Ree

    2014-01-01

    Background In June 2013 a one-day workshop on Dynamic Treatment Strategies (DTS) and Sequential Multiple Assignment Randomized Trials (SMART) was held at the University of Pennsylvania in Philadelphia, PA. These two linked topics have generated a great deal of interest as researchers have recognized the importance of comparing entire strategies for managing chronic disease. A number of articles emerged from that workshop. Purpose The purpose of this survey of the DTS/SMART methodology (which is taken from the introductory talk in the workshop) is to provide the reader of the collected articles presented in this volume with sufficient background to appreciate the more detailed discussions in the papers. Methods The way that the DTS arises naturally in clinical practice is described, along with its connection to the well-known difficulties of intepreting the analysis by intention-to-treat. The SMART methodology for comparing DTS is described, and the basics of estimation and inference presented. Results The DTS/SMART methodology can be a flexible and practical way to optimize ongoing clinical decision making, providing evidence (based on randomization) for comparative effectiveness. Limitations The DTS/SMART methodology is not a solution for unstandardized study protocols. Conclusions The DTS/SMART methodology has growing relevance to comparative effectiveness research and the needs of the learning healthcare system. PMID:24784487

  1. Impaired movement timing in neurological disorders: rehabilitation and treatment strategies

    PubMed Central

    Hove, Michael J.; Keller, Peter E.

    2014-01-01

    Timing abnormalities have been reported in many neurological disorders, including Parkinson’s disease (PD). In PD, motor-timing impairments are especially debilitating in gait. Despite impaired audiomotor synchronization, PD patients’ gait improves when they walk with an auditory metronome or with music. Building on that research, we make recommendations for optimizing sensory cues to improve the efficacy of rhythmic cuing in gait rehabilitation. Adaptive rhythmic metronomes (that synchronize with the patient’s walking) might be especially effective. In a recent study we showed that adaptive metronomes synchronized consistently with Parkinson patients’ footsteps without requiring attention; this improved stability and reinstated healthy gait dynamics. Other strategies could help optimize sensory cues for gait rehabilitation. Groove music strongly engages the motor system and induces movement; bass-frequency tones are associated with movement and provide strong timing cues. Thus, groove and bass-frequency pulses could deliver potent rhythmic cues. These strategies capitalize on the close neural connections between auditory and motor networks; and auditory cues are typically preferred. However, moving visual cues greatly improve visuomotor synchronization and could warrant examination in gait rehabilitation. Together, a treatment approach that employs groove, auditory, bass-frequency, and adaptive (GABA) cues could help optimize rhythmic sensory cues for treating motor and timing deficits. PMID:25773624

  2. Augmentation strategies for treatment-resistant depression: a literature review.

    PubMed

    Carvalho, A F; Cavalcante, J L; Castelo, M S; Lima, M C O

    2007-10-01

    The large majority of depressed patients fail to remit on the first antidepressant prescribed. These patients with residual symptoms have higher relapse rates and poorer outcomes than those who remit. Treatment-resistant depression (TRD) is a therapeutic challenge for the clinician. Augmentation pharmacotherapy refers to the addition of drugs that are not standard antidepressants in order to enhance the effect of a classical antidepressant drug. The aim of this paper was to review the available evidence on the various augmenting agents that have been tested for efficacy in TRD. Electronic databases and relevant textbooks were searched and the information retrieved was integrated in this review. Although augmentation strategies have been tested with various pharmacological agents, there are few controlled studies published. Lithium, triiodothyronine (T3), buspirone and pindolol have been most widely studied. Other agents include dopaminergic agents, atypical antipsychotics, psychostimulants, benzodiazepines/hypnotics, hormones and anticonvulsants. The augmentation therapy with the best evidence was the lithium-antidepressant combination, especially in patients not responding to tricyclic agents. However, good results have also been reported with augmentation strategies involving T3 and buspirone.

  3. Biomedical engineering strategies for peripheral nerve repair: surgical applications, state of the art, and future challenges.

    PubMed

    Pfister, Bryan J; Gordon, Tessa; Loverde, Joseph R; Kochar, Arshneel S; Mackinnon, Susan E; Cullen, D Kacy

    2011-01-01

    Damage to the peripheral nervous system is surprisingly common and occurs primarily from trauma or a complication of surgery. Although recovery of nerve function occurs in many mild injuries, outcomes are often unsatisfactory following severe trauma. Nerve repair and regeneration presents unique clinical challenges and opportunities, and substantial contributions can be made through the informed application of biomedical engineering strategies. This article reviews the clinical presentations and classification of nerve injuries, in addition to the state of the art for surgical decision-making and repair strategies. This discussion presents specific challenges that must be addressed to realistically improve the treatment of nerve injuries and promote widespread recovery. In particular, nerve defects a few centimeters in length use a sensory nerve autograft as the standard technique; however, this approach is limited by the availability of donor nerve and comorbidity associated with additional surgery. Moreover, we currently have an inadequate ability to noninvasively assess the degree of nerve injury and to track axonal regeneration. As a result, wait-and-see surgical decisions can lead to undesirable and less successful "delayed" repair procedures. In this fight for time, degeneration of the distal nerve support structure and target progresses, ultimately blunting complete functional recovery. Thus, the most pressing challenges in peripheral nerve repair include the development of tissue-engineered nerve grafts that match or exceed the performance of autografts, the ability to noninvasively assess nerve damage and track axonal regeneration, and approaches to maintain the efficacy of the distal pathway and targets during the regenerative process. Biomedical engineering strategies can address these issues to substantially contribute at both the basic and applied levels, improving surgical management and functional recovery following severe peripheral nerve injury.

  4. Novel Strategies in the Prevention and Treatment of Urinary Tract Infections

    PubMed Central

    Lüthje, Petra; Brauner, Annelie

    2016-01-01

    Urinary tract infections are one of the most common bacterial infections, especially in women and children, frequently treated with antibiotics. The alarming increase in antibiotic resistance is a global threat to future treatment of infections. Therefore, alternative strategies are urgently needed. The innate immune system plays a fundamental role in protecting the urinary tract from infections. Antimicrobial peptides form an important part of the innate immunity. They are produced by epithelial cells and neutrophils and defend the urinary tract against invading bacteria. Since efficient resistance mechanisms have not evolved among bacterial pathogens, much effort has been put into exploring the role of antimicrobial peptides and possibilities to utilize them in clinical practice. Here, we describe the impact of antimicrobial peptides in the urinary tract and ways to enhance the production by hormones like vitamin D and estrogen. We also discuss the potential of medicinal herbs to be used in the prophylaxis and the treatment of urinary tract infections. PMID:26828523

  5. Pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders.

    PubMed

    Ipser, J C; Carey, P; Dhansay, Y; Fakier, N; Seedat, S; Stein, D J

    2006-10-18

    (SMD) -0.87, 95% CI -1.37 to -0.36). There is no evidence of a difference between medication and placebo in total dropout rate, or in the number of dropouts due to adverse events. Medication augmentation can be an effective and well-tolerated short-term treatment strategy for non-responders to first-line pharmacotherapy of anxiety disorders. However, any conclusions must be tentative in view of methodological and clinical heterogeneity, and the fact that much of the relevant database is based on antipsychotic augmentation trials in OCD patients resistant to serotonin reuptake inhibitors (SRIs). Additional data are needed to address several areas, including the efficacy of augmentation over the longer-term, and the value of medication augmentation in comparison to other strategies (e.g. switching medication, adding psychotherapy).

  6. Monoaminergic and Histaminergic Strategies and Treatments in Brain Diseases

    PubMed Central

    Di Giovanni, Giuseppe; Svob Strac, Dubravka; Sole, Montse; Unzeta, Mercedes; Tipton, Keith F.; Mück-Šeler, Dorotea; Bolea, Irene; Della Corte, Laura; Nikolac Perkovic, Matea; Pivac, Nela; Smolders, Ilse J.; Stasiak, Anna; Fogel, Wieslawa A.; De Deurwaerdère, Philippe

    2016-01-01

    The monoaminergic systems are the target of several drugs for the treatment of mood, motor and cognitive disorders as well as neurological conditions. In most cases, advances have occurred through serendipity, except for Parkinson's disease where the pathophysiology led almost immediately to the introduction of dopamine restoring agents. Extensive neuropharmacological studies first showed that the primary target of antipsychotics, antidepressants, and anxiolytic drugs were specific components of the monoaminergic systems. Later, some dramatic side effects associated with older medicines were shown to disappear with new chemical compounds targeting the origin of the therapeutic benefit more specifically. The increased knowledge regarding the function and interaction of the monoaminergic systems in the brain resulting from in vivo neurochemical and neurophysiological studies indicated new monoaminergic targets that could achieve the efficacy of the older medicines with fewer side-effects. Yet, this accumulated knowledge regarding monoamines did not produce valuable strategies for diseases where no monoaminergic drug has been shown to be effective. Here, we emphasize the new therapeutic and monoaminergic-based strategies for the treatment of psychiatric diseases. We will consider three main groups of diseases, based on the evidence of monoamines involvement (schizophrenia, depression, obesity), the identification of monoamines in the diseases processes (Parkinson's disease, addiction) and the prospect of the involvement of monoaminergic mechanisms (epilepsy, Alzheimer's disease, stroke). In most cases, the clinically available monoaminergic drugs induce widespread modifications of amine tone or excitability through neurobiological networks and exemplify the overlap between therapeutic approaches to psychiatric and neurological conditions. More recent developments that have resulted in improved drug specificity and responses will be discussed in this review. PMID

  7. Innovative strategies for the treatment of thyroid cancer.

    PubMed

    Schmutzler, C; Koehrle, J

    2000-07-01

    Normally, thyroid cancer is a disease with a good prognosis, but about 30% of the tumours dedifferentiate and may finally develop into highly malignant anaplastic thyroid carcinomas with a mean survival time of less than 8 months. Due to the loss of thyroid-specific functions associated with dedifferentiation, these tumours are inaccessible to standard therapeutic procedures such as radioiodide therapy and thyroxine-mediated thyrotrophin suppression. Medullary thyroid carcinomas are also highly aggressive. Here, therapy is limited to surgery, and no alternative is left if patients do not respond to this standard procedure. Obviously, new approaches would be desirable. Several novel approaches are currently being tested for the treatment of thyroid cancer. Many of them utilise methods of gene therapy, but follow different strategies: (1) reintroduction of the tumour suppressor p53 into a background lacking functional p53; (2) suicide gene therapy with ganciclovir and a transduced gene for herpes simplex virus thymidine kinase controlled by the thyroglobulin promoter; (3) strengthening of the antitumour immune response by expression of an adenovirus-delivered interleukin-2 (IL-2) gene; (4) induction of an immune response by DNA vaccination against the tumour marker calcitonin; (5) transduction of the thyroid sodium/iodide transporter gene to make tissues that do not accumulate iodide treatable by radioiodide therapy; (6) blocking of the expression of the oncogene c-myc by antisense oligonucleotides. While these approaches are still tested in vitro or in animal models, first results from pilot studies concerning other novel treatment modalities are available: (7) radioimmunotherapy exploits the carcinoembryonic antigen expressed on medullary thyroid carcinomas to target a radiolabelled antibody to the tumour; and (8) retinoic acid is used for a redifferentiation therapy in the case of thyroid cancer. Hopefully, one or the other of these novel strategies may probably

  8. The History and Future of Treatment of Hypothyroidism.

    PubMed

    McAninch, Elizabeth A; Bianco, Antonio C

    2016-01-05

    Thyroid hormone replacement has been used for more than a century to treat hypothyroidism. Natural thyroid preparations (thyroid extract, desiccated thyroid, or thyroglobulin), which contain both thyroxine (T4) and triiodothyronine (T3), were the first pharmacologic treatments available and dominated the market for the better part of the 20th century. Dosages were adjusted to resolve symptoms and to normalize the basal metabolic rate and/or serum protein-bound iodine level, but thyrotoxic adverse effects were not uncommon. Two major developments in the 1970s led to a transition in clinical practice: 1) The development of the serum thyroid-stimulating hormone (TSH) radioimmunoassay led to the discovery that many patients were overtreated, resulting in a dramatic reduction in thyroid hormone replacement dosage, and 2) the identification of peripheral deiodinase-mediated T4-to-T3 conversion provided a physiologic means to justify l-thyroxine monotherapy, obviating concerns about inconsistencies with desiccated thyroid. Thereafter, l-thyroxine monotherapy at doses to normalize the serum TSH became the standard of care. Since then, a subgroup of thyroid hormone-treated patients with residual symptoms of hypothyroidism despite normalization of the serum TSH has been identified. This has brought into question the inability of l-thyroxine monotherapy to universally normalize serum T3 levels. New research suggests mechanisms for the inadequacies of l-thyroxine monotherapy and highlights the possible role for personalized medicine based on deiodinase polymorphisms. Understanding the historical events that affected clinical practice trends provides invaluable insight into formulation of an approach to help all patients achieve clinical and biochemical euthyroidism.

  9. The History and Future of Treatment of Hypothyroidism

    PubMed Central

    McAninch, Elizabeth A.; Bianco, Antonio C.

    2016-01-01

    Thyroid hormone replacement has been used for more than a century to treat hypothyroidism. Natural thyroid preparations (thyroid extract, desiccated thyroid, or thyroglobulin), which contain both thyroxine (T4) and triiodothyronine (T3), were the first pharmacologic treatments available and dominated the market for the better part of the 20th century. Dosages were adjusted to resolve symptoms and to normalize the basal metabolic rate and/or serum protein-bound iodine level, but thyrotoxic adverse effects were not uncommon. Two major developments in the 1970s led to a transition in clinical practice: 1) The development of the serum thyroid-stimulating hormone (TSH) radioimmunoassay led to the discovery that many patients were overtreated, resulting in a dramatic reduction in thyroid hormone replacement dosage, and 2) the identification of peripheral deiodinase-mediated T4-to-T3 conversion provided a physiologic means to justify l-thyroxine monotherapy, obviating concerns about inconsistencies with desiccated thyroid. Thereafter, l-thyroxine mono-therapy at doses to normalize the serum TSH became the standard of care. Since then, a subgroup of thyroid hormone–treated patients with residual symptoms of hypothyroidism despite normalization of the serum TSH has been identified. This has brought into question the inability of l-thyroxine monotherapy to universally normalize serum T3 levels. New research suggests mechanisms for the inadequacies of l-thyroxine monotherapy and highlights the possible role for personalized medicine based on deiodinase polymorphisms. Understanding the historical events that affected clinical practice trends provides invaluable insight into formulation of an approach to help all patients achieve clinical and biochemical euthyroidism. PMID:26747302

  10. Strategies in treatment of suicidality: identification of common and treatment-specific interventions in empirically supported treatment manuals.

    PubMed

    Weinberg, Igor; Ronningstam, Elsa; Goldblatt, Mark J; Schechter, Mark; Wheelis, Joan; Maltsberger, John T

    2010-06-01

    Many reports of treatments for suicidal patients claim effectiveness in reducing suicidal behavior but fail to demonstrate which treatment interventions, or combinations thereof, diminish suicidality. In this study, treatment manuals for empirically supported psychological treatments for suicidal patients were examined to identify which interventions they had in common and which interventions were treatment-specific. Empirically supported treatments for suicidality were identified through a literature search of PsychLit and MEDLINE for the years 1970-2007, employing the following search strategy: [suicide OR parasuicide] AND [therapy OR psychotherapy OR treatment] AND [random OR randomized]. After identifying the reports on randomized controlled studies that tested effectiveness of different treatments, the reference list of each report was searched for further studies. Only reports published in English were included. To ensure that rated manuals actually correspond to the delivered and tested treatments, we included only treatment interventions with explicit adherence rating and scoring and with adequate adherence ratings in the published studies. Five manualized treatments demonstrating efficacy in reducing suicide risk were identified and were independently evaluated by raters using a list of treatment interventions. The common interventions included a clear treatment framework; a defined strategy for managing suicide crises; close attention to affect; an active, participatory therapist style; and use of exploratory and change-oriented interventions. Some treatments encouraged a multimodal approach and identification of suicidality as an explicit target behavior, and some concentrated on the patient-therapist relationship. Emphasis on interpretation and supportive interventions varied. Not all methods encouraged systematic support for therapists. This study identified candidate interventions for possible effectiveness in reducing suicidality. These interventions

  11. Factors influencing the prescription of intensive combination treatment strategies for early rheumatoid arthritis.

    PubMed

    Meyfroidt, S; van Hulst, L; De Cock, D; Van der Elst, K; Joly, J; Westhovens, R; Hulscher, M; Verschueren, P

    2014-01-01

    Despite the availability and demonstrated effectiveness of intensive combination treatment strategies (ICTS) for early rheumatoid arthritis (RA), a discrepancy seems to exist between theoretical evidence and actual prescription in daily practice. The purpose of this study was to explore and identify the factors influencing the prescription of ICTS. This study involved rheumatologists and nurses participating in the Care for Rheumatoid Arthritis (CareRA) trial, a multicentre randomized controlled trial (RCT) comparing different ICTS for early RA with conventional disease-modifying anti-rheumatic drugs (DMARDs) plus step-down glucocorticoids (GCs). A qualitative study was carried out using individual semi-structured interviews. Each interview was recorded, transcribed literally, and analysed thematically. In addition, observations at outpatient clinics were used to clarify the interpretation of the results. We interviewed 26 rheumatologists and six nurses and observed five outpatient visits. Identified facilitators included available scientific evidence, personal faith in treatment strategy, staff support, and low treatment costs. Rheumatologists had no doubts about the value of methotrexate (MTX) but some questioned the value of combination strategy, others the effectiveness and/or the dosage of individual compounds. Additional barriers for prescribing ICTS included need for patient education, fear for patients' preconceptions, concerns about applicability to the individual patient, difficulties with breaking routine, interference with organizational structures and processes, time constraints, and lack of financial support. A heterogeneous set of factors highlights the complexity of prescribing ICTS for early RA in daily clinical practice. Future improvement strategies should stimulate the facilitators while at the same time addressing the barriers. The generalizability of these findings to other health care systems needs further examination.

  12. Hyperthermia in cancer treatment: current and future prospects.

    PubMed

    U, R; Noell, K T; Worde, B T; Woodward, K T; Fishburn, R I; Miller, L S; Herskovic, A M

    1982-03-01

    potentially significant impact on clinical cancer therapy, whether of curative or palliative intent, by moderate thermotherapy is evident. Technical advances to optimize such treatment methods including R & D for delivering a known localized quantity of heat to tumors in any location in the body are expected to progress rapidly. The methods with most promising potential for inducing local thermotherapy are those involving the use of electromagnetic waves, e.g., radiofrequency energy, microwave energy, and ultrasound energy.

  13. Targeting MIF in Cancer: Therapeutic Strategies, Current Developments, and Future Opportunities.

    PubMed

    O'Reilly, Ciaran; Doroudian, Mohammad; Mawhinney, Leona; Donnelly, Seamas C

    2016-05-01

    Strong evidence has been presented linking chronic inflammation to the onset and pathogenesis of cancer. The multifunctional pro-inflammatory protein macrophage migration inhibitory factor (MIF) occupies a central role in the inflammatory pathway and has been implicated in the tumorigenesis, angiogenesis, and metastasis of many cancer phenotypes. This review highlights the current state of the art, which presents MIF, and the second member of the MIF structural superfamily, D-DT (MIF2), as significant mediators in the inflammatory-cancer axis. Although the mechanism by which MIF asserts its biological activity has yet to be fully understood, it has become clear in recent years that for certain phenotypes of cancer, MIF represents a valid therapeutic target. Current research efforts have focused on small molecule approaches that target MIF's unique tautomerase active site and neutralization of MIF with anti-MIF antibodies. These approaches have yielded promising results in a number of preclinical murine cancer models and have helped to increase our understanding of MIF biological activity. More recently, MIF's involvement in a number of key protein-protein interactions, such as with CD74 and HSP90, has been highlighted and provides a novel platform for the development of anti-MIF chemotherapeutic strategies in the future.

  14. Biobanking of Human Mesenchymal Stem Cells: Future Strategy to Facilitate Clinical Applications.

    PubMed

    Yong, Kar Wey; Choi, Jane Ru; Wan Safwani, Wan Kamarul Zaman

    2016-01-01

    Human mesenchymal stem cells (hMSCs), a type of adult stem cells that hold great potential in clinical applications (e.g., regenerative medicine and cell-based therapy) due to their ability to differentiate into multiple types of specialized cells and secrete soluble factors which can initiate tissue repair and regulate immune response. hMSCs need to be expanded in vitro or cryopreserved to obtain sufficient cell numbers required for clinical applications. However, long-term in vitro culture-expanded hMSCs may raise some biosafety concerns (e.g., chromosomal abnormality and malignant transformation) and compromised functional properties, limiting their use in clinical applications. To avoid those adverse effects, it is essential to cryopreserve hMSCs at early passage and pool them for off-the-shelf use in clinical applications. However, the existing cryopreservation methods for hMSCs have some notable limitations. To address these limitations, several approaches have to be taken in order to produce healthy and efficacious cryopreserved hMSCs for clinical trials, which remains challenging to date. Therefore, a noteworthy amount of resources has been utilized in research in optimization of the cryopreservation methods, development of freezing devices, and formulation of cryopreservation media to ensure that hMSCs maintain their therapeutic characteristics without raising biosafety concerns following cryopreservation. Biobanking of hMSCs would be a crucial strategy to facilitate clinical applications in the future.

  15. The dieselization of America: An integrated strategy for future transportation fuels

    SciTech Connect

    Eberhardt, J.J.

    1997-12-31

    The Diesel Cycle engine has already established itself as the engine-of-choice for the heavy duty transport industry because of its fuel efficiency, durability, and reliability. In addition, it has also been shown to be capable of using alternative fuels, albeit at efficiencies lower than that achieved with petroleum-derived diesel fuel. Alternative fuel dedicated engines have not made significant penetration of the heavy duty truck market because truck fleet operators need a cost-competitive fuel and reliable supply and fueling infrastructure. In lieu of forcing diverse fuels from many diverse domestic feedstocks onto the end-users, the Office of Heavy Vehicle Technologies envisions that a future fuels strategy for the heavy duty transport sector is one where the diverse feedstocks are utilized to provide a single fuel specification (dispensed from the existing fueling infrastructure) that would run efficiently in a single high efficiency energy conversion device, the Diesel Cycle engine. In so doing, the US Commercial transport industry may gain a measure of security from the rapid fuel price increases by relying less on a single feedstock source to meet its increasing fuel requirements.

  16. A wedge strategy for mitigation of urban warming in future climate scenarios

    NASA Astrophysics Data System (ADS)

    Zhao, L.

    2016-12-01

    Heat stress is one of the most severe climate threats to the human society in a future warmer world. The situation is further compounded in urban areas by the urban heat island (UHI). Because the majority of the world's population is projected to live in cities, there is a pressing need to find effective solutions for the high temperature problem. It is now recognized that in addition to the traditional emphasis on preparedness to cope with heat stress, these solutions should include active modifications of urban land form to reduce urban temperatures. Here we use an urban climate model to investigate the effectiveness of these active methods in mitigating the urban heat, both individually and collectively. By adopting highly reflective roofs citywide, almost all the cities in the USA and in southern Canada are transformed into cold islands or "white oases" where the daytime surface temperatures are lower than those in the surrounding rural land. The average oasis effect is -3.4 ± 0.3 K (mean ± 1 standard error) for the period 2071-2100 under the RCP4.5 scenario. A UHI mitigation wedge strategy consisting of cool roof, street vegetation and reflective pavement has the potential to eliminate the daytime UHI plus the greenhouse gas induced warming.

  17. Future needs and strategies for coupled permafrost and terrestrial hydrology simulations

    NASA Astrophysics Data System (ADS)

    Painter, S. L.; Coon, E.; Jan, A.; Moulton, J. D.; Thornton, P. E.; Wilson, C. J.

    2016-12-01

    Permafrost degradation in a warming climate has the potential to adversely affect Arctic infrastructure and produce carbon and energy feedbacks to the atmosphere. The need to understand those potential impacts and feedbacks has prompted recent efforts to develop integrated surface/subsurface thermal hydrology simulation capability for permafrost-affected regions. We will summarize the current state and future needs for physically based permafrost thermal hydrology simulators. Four priority needs beyond the current state of the art have been identified: capability to represent dynamic topography caused by melting of massive ground ice, improved numerical performance of physically based simulators, approaches for representing effects of subgrid variability in regional to pan-Arctic scale simulations, and representation of thermal effects of vegetation changes. Strategies and ongoing efforts to implement the needed capability will also be described. This work was supported by the Next Generation Ecosystem Experiment (NGEE-Arctic) project, and the Interoperable Design of Extreme-scale Application Software (IDEAS) Project. NGEE-Arctic is supported by the Office of Biological and Environmental Research in the DOE Office of Science.

  18. The Future of Public Health Informatics: Alternative Scenarios and Recommended Strategies

    PubMed Central

    Edmunds, Margo; Thorpe, Lorna; Sepulveda, Martin; Bezold, Clem; Ross, David A.

    2014-01-01

    Background: In October 2013, the Public Health Informatics Institute (PHII) and Institute for Alternative Futures (IAF) convened a multidisciplinary group of experts to evaluate forces shaping public health informatics (PHI) in the United States, with the aim of identifying upcoming challenges and opportunities. The PHI workshop was funded by the Robert Wood Johnson Foundation as part of its larger strategic planning process for public health and primary care. Workshop Context: During the two-day workshop, nine experts from the public and private sectors analyzed and discussed the implications of four scenarios regarding the United States economy, health care system, information technology (IT) sector, and their potential impacts on public health in the next 10 years, by 2023. Workshop participants considered the potential role of the public health sector in addressing population health challenges in each scenario, and then identified specific informatics goals and strategies needed for the sector to succeed in this role. Recommendations and Conclusion: Participants developed recommendations for the public health informatics field and for public health overall in the coming decade. These included the need to rely more heavily on intersectoral collaborations across public and private sectors, to improve data infrastructure and workforce capacity at all levels of the public health enterprise, to expand the evidence base regarding effectiveness of informatics-based public health initiatives, and to communicate strategically with elected officials and other key stakeholders regarding the potential for informatics-based solutions to have an impact on population health. PMID:25848630

  19. The Past, Present, and Potential Future of Sodium Channel Block as an Atrial Fibrillation Suppressing Strategy.

    PubMed

    Aguilar, Martin; Nattel, Stanley

    2015-11-01

    Despite major advances in arrhythmia therapy, atrial fibrillation (AF) remains a challenge. A significant limitation in AF management is the lack of safe and effective drugs to restore and/or maintain sinus rhythm. The rational design of a new generation of AF-selective Na(+) channel blockers (NCBs) is emerging as a promising AF-suppressing strategy. Recent theoretical and experimental advances have generated insights into the mechanisms underlying AF maintenance and termination by antiarrhythmic drugs. Our understanding of antiarrhythmic drug-induced proarrhythmia has also grown in sophistication. These discoveries have created new possibilities in therapeutic targeting and renewed interest in improved NCB antiarrhythmic drugs. Recently described differences in atrial versus ventricular electrophysiology can be exploited in the prospective design of atrial-selective NCBs. Furthermore, state-dependent block has been shown to be an important modulator of NCB rate selectivity. Together, differential atrial-ventricular electrophysiological actions and state-dependent block form the backbone for the rational design of an AF-selective NCB. Synergistic combinations incorporating both NCB and block of K(+) currents may allow for further enhancement of AF selectivity. Future work on translating these basic research advances into the development of an optimized AF-selective NCB has the potential to provide safer and more effective pharmacotherapeutic options for AF, thereby fulfilling a major unmet clinical need.

  20. Breaking the Cycle: Future Faculty Begin Teaching with Learner-Centered Strategies after Professional Development

    PubMed Central

    Ebert-May, Diane; Derting, Terry L.; Henkel, Timothy P.; Middlemis Maher, Jessica; Momsen, Jennifer L.; Arnold, Bryan; Passmore, Heather A.

    2015-01-01

    The availability of reliable evidence for teaching practices after professional development is limited across science, technology, engineering, and mathematics disciplines, making the identification of professional development “best practices” and effective models for change difficult. We aimed to determine the extent to which postdoctoral fellows (i.e., future biology faculty) believed in and implemented evidence-based pedagogies after completion of a 2-yr professional development program, Faculty Institutes for Reforming Science Teaching (FIRST IV). Postdocs (PDs) attended a 2-yr training program during which they completed self-report assessments of their beliefs about teaching and gains in pedagogical knowledge and experience, and they provided copies of class assessments and video recordings of their teaching. The PDs reported greater use of learner-centered compared with teacher-centered strategies. These data were consistent with the results of expert reviews of teaching videos. The majority of PDs (86%) received video ratings that documented active engagement of students and implementation of learner-centered classrooms. Despite practice of higher-level cognition in class sessions, the items used by the PDs on their assessments of learning focused on lower-level cognitive skills. We attributed the high success of the FIRST IV program to our focus on inexperienced teachers, an iterative process of teaching practice and reflection, and development of and teaching a full course. PMID:26033870

  1. A wedge strategy for mitigation of urban warming in future climate scenarios

    NASA Astrophysics Data System (ADS)

    Zhao, Lei; Lee, Xuhui; Schultz, Natalie M.

    2017-07-01

    Heat stress is one of the most severe climate threats to human society in a future warmer world. The situation is further exacerbated in urban areas by urban heat islands (UHIs). Because the majority of world's population is projected to live in cities, there is a pressing need to find effective solutions for the heat stress problem. We use a climate model to investigate the effectiveness of various urban heat mitigation strategies: cool roofs, street vegetation, green roofs, and reflective pavement. Our results show that by adopting highly reflective roofs, almost all the cities in the United States and southern Canada are transformed into white oases - cold islands caused by cool roofs at midday, with an average oasis effect of -3.4 K in the summer for the period 2071-2100, which offsets approximately 80 % of the greenhouse gas (GHG) warming projected for the same period under the RCP4.5 scenario. A UHI mitigation wedge consisting of cool roofs, street vegetation, and reflective pavement has the potential to eliminate the daytime UHI plus the GHG warming.

  2. Breaking the cycle: future faculty begin teaching with learner-centered strategies after professional development.

    PubMed

    Ebert-May, Diane; Derting, Terry L; Henkel, Timothy P; Middlemis Maher, Jessica; Momsen, Jennifer L; Arnold, Bryan; Passmore, Heather A

    2015-01-01

    The availability of reliable evidence for teaching practices after professional development is limited across science, technology, engineering, and mathematics disciplines, making the identification of professional development "best practices" and effective models for change difficult. We aimed to determine the extent to which postdoctoral fellows (i.e., future biology faculty) believed in and implemented evidence-based pedagogies after completion of a 2-yr professional development program, Faculty Institutes for Reforming Science Teaching (FIRST IV). Postdocs (PDs) attended a 2-yr training program during which they completed self-report assessments of their beliefs about teaching and gains in pedagogical knowledge and experience, and they provided copies of class assessments and video recordings of their teaching. The PDs reported greater use of learner-centered compared with teacher-centered strategies. These data were consistent with the results of expert reviews of teaching videos. The majority of PDs (86%) received video ratings that documented active engagement of students and implementation of learner-centered classrooms. Despite practice of higher-level cognition in class sessions, the items used by the PDs on their assessments of learning focused on lower-level cognitive skills. We attributed the high success of the FIRST IV program to our focus on inexperienced teachers, an iterative process of teaching practice and reflection, and development of and teaching a full course.

  3. Genomics, microRNA, epigenetics, and proteomics for future diagnosis, treatment and monitoring response in upper GI cancers.

    PubMed

    Brücher, Björn L D M; Li, Yan; Schnabel, Philipp; Daumer, Martin; Wallace, Timothy J; Kube, Rainer; Zilberstein, Bruno; Steele, Scott; Voskuil, Jan L A; Jamall, Ijaz S

    2016-03-01

    One major objective for our evolving understanding in the treatment of cancers will be to address how a combination of diagnosis and treatment strategies can be used to integrate patient and tumor variables with an outcome-oriented approach. Such an approach, in a multimodal therapy setting, could identify those patients (1) who should undergo a defined treatment (personalized therapy) (2) in whom modifications of the multimodal therapy due to observed responses might lead to an improvement of the response and/or prognosis (individualized therapy), (3) who might not benefit from a particular toxic treatment regimen, and (4) who could be identified early on and thereby be spared the morbidity associated with such treatments. These strategies could lead in the direction of precision medicine and there is hope of integrating translational molecular data to improve cancer classifications. In order to achieve these goals, it is necessary to understand the key issues in different aspects of biotechnology to anticipate future directions of personalized and individualized diagnosis and multimodal treatment strategies. Providing an overview of translational data in cancers proved to be a challenge as different methods and techniques used to obtain molecular data are used and studies are based on different tumor entities with different tumor biology and prognoses as well as vastly different therapeutic approaches. The pros and cons of the available methodologies and the potential response data in genomics, microRNA, epigenetics and proteomics with a focus on upper gastrointestinal cancers are considered herein to allow for an understanding of where these technologies stand with respect to cancer diagnosis, prognosis and treatment.

  4. Strategy for the treatment of Helicobacter pylori infection.

    PubMed

    Shiota, Seiji; Yamaoka, Yoshio

    2014-01-01

    The eradication of Helicobacter pylori not only heals peptic ulcers but also prevents their recurrence and reduces the risk of development of gastric cancer and other H. pylori-associated disorders. H. pylori eradication heals gastritis and may prevent the spread of infection, reducing the future costs required for the treatment of subsequent H. pylori-associated diseases. There are various guidelines for the management of H. pylori infection worldwide, such as the guidelines of the American College of Gastroenterology, Maastricht IV, the Second Asia-Pacific Consensus Conference, and Japan. The Japanese health insurance system approved H. pylori eradication therapy for H. pylori-related chronic gastritis in 2013. Triple therapy regimens comprising 1 proton pump inhibitor and 2 antimicrobial agents such as amoxicillin, clarithromycin, metronidazole, levofloxacin, or tetracycline have been widely used to eradicate this bacterium. The rate of successful eradication has declined owing to the increased rate of drug resistance stemming from the wide usage of antibiotics. This issue is of particular relevance with regard to clarithromycin. In worldwide, clarithromycin-based triple therapy should be abandoned, as it is no longer effective. Quadruple therapy and sequential therapy are reasonable alternatives for initial therapy. First-line treatment should be recommended on the basis of an understanding of the local prevalence of H. pylori antimicrobial resistance.

  5. Lenalidomide for treatment of myelodysplastic syndromes: current status and future directions.

    PubMed

    Komrokji, Rami S; List, Alan F

    2010-04-01

    Lenalidomide was approved by the US Food and Drug Administration (FDA) for treatment of transfusion-dependent lower-risk myelodysplastic syndrome patients with deletion (del) (5q) alone or with additional karyotype abnormalities. The approval was based on high rates of prolonged transfusion independence and complete cytogenetic response in this subset. In lower-risk non-del(5q) patients, meaningful erythroid responses also were reported with a low frequency of cytogenetic improvement, although inferior to that observed in the del(5q) patients. There is now a better understanding of the mechanism of the karyotype-dependent drug action, explaining the disparate response rates and frequency of myelosuppression. In del(5q) patients, lenalidomide suppresses the clone by inhibiting the nuclear sequestration of the haplodeficient cell cycle regulatory protein cdc25c, thereby promoting selective G2 arrest and apoptosis. In non-del(5q) patients, lenalidomide enhances erythropoietin receptor signaling. Future directions include use of biologic and molecular markers as predictive tools to select patients and use of combination strategies to overcome resistance to lenalidomide in del(5q) patients or enhance erythropoiesis in non-del 5 patients. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  6. Various Strategies for Pain-Free Root Canal Treatment

    PubMed Central

    Parirokh, Masoud; V. Abbott, Paul

    2014-01-01

    Introduction: Achieving successful anesthesia and performing pain-free root canal treatment are important aims in dentistry. This is not always achievable and therefore, practitioners are constantly seeking newer techniques, equipments, and anesthetic solutions for this very purpose. The aim of this review is to introduce strategies to achieve profound anesthesia particularly in difficult cases. Materials and Methods: A review of the literature was performed by electronic and hand searching methods for anesthetic agents, techniques, and equipment. The highest level of evidence based investigations with rigorous methods and materials were selected for discussion. Results: Numerous studies investigated to pain management during root canal treatment; however, there is still no single technique that will predictably provide profound pulp anesthesia. One of the most challenging issues in endodontic practice is achieving a profound anesthesia for teeth with irreversible pulpitis especially in mandibular posterior region. Conclusion: According to most investigations, achieving a successful anesthesia is not always possible with a single technique and practitioners should be aware of all possible alternatives for profound anesthesia. PMID:24396370

  7. Current strategies for prevention, detection, and treatment of ovarian cancer.

    PubMed

    Shepherd, J E

    2000-01-01

    To review the prevalence, etiology, risk factors, diagnosis, and treatment of ovarian cancer. English-language journal articles retrieved from a MEDLINE search from 1990 to the present, and selected references retrieved from the bibliographies of those articles. Clinical trials and pertinent review articles that discussed the detection, prevention, and clinical management of ovarian cancer. Although relatively uncommon, ovarian cancer is the leading cause of mortality from gynecologic cancer. Because most ovarian cancers are not detected until the disease has metastasized beyond the ovary, the 5-year survival rate for all cases is only 50%. Pharmacists can educate women about strategies that can reduce ovarian cancer risk, especially the use of oral contraceptives. To aid in earlier detection, pharmacists also should be aware of the nonspecific symptoms that can be associated with the disease, and refer women with suggestive symptoms to their physicians for further evaluation. Treatment usually consists of hysterectomy with debulking surgery to remove as much tumor as possible, followed by chemotherapy, for which the current gold standard is cisplatin and paclitaxel. Pharmacist-provided education can help women reduce their risk of ovarian cancer. As integral members of the health care team, pharmacists also can optimize the efficacy and tolerability of chemotherapeutic regimens; assist with palliative care for nausea, vomiting, and pain; and serve as a resource for patient information and support.

  8. Current Research Therapeutic Strategies for Alzheimer's Disease Treatment

    PubMed Central

    Folch, Jaume; Petrov, Dmitry; Ettcheto, Miren; Abad, Sonia; Sánchez-López, Elena; García, M. Luisa; Olloquequi, Jordi; Beas-Zarate, Carlos; Auladell, Carme; Camins, Antoni

    2016-01-01

    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. PMID:26881137

  9. Current Research Therapeutic Strategies for Alzheimer's Disease Treatment.

    PubMed

    Folch, Jaume; Petrov, Dmitry; Ettcheto, Miren; Abad, Sonia; Sánchez-López, Elena; García, M Luisa; Olloquequi, Jordi; Beas-Zarate, Carlos; Auladell, Carme; Camins, Antoni

    2016-01-01

    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.

  10. Using Chemical Reaction Kinetics to Predict Optimal Antibiotic Treatment Strategies

    PubMed Central

    Abel zur Wiesch, Pia; Cohen, Ted

    2017-01-01

    Identifying optimal dosing of antibiotics has proven challenging—some antibiotics are most effective when they are administered periodically at high doses, while others work best when minimizing concentration fluctuations. Mechanistic explanations for why antibiotics differ in their optimal dosing are lacking, limiting our ability to predict optimal therapy and leading to long and costly experiments. We use mathematical models that describe both bacterial growth and intracellular antibiotic-target binding to investigate the effects of fluctuating antibiotic concentrations on individual bacterial cells and bacterial populations. We show that physicochemical parameters, e.g. the rate of drug transmembrane diffusion and the antibiotic-target complex half-life are sufficient to explain which treatment strategy is most effective. If the drug-target complex dissociates rapidly, the antibiotic must be kept constantly at a concentration that prevents bacterial replication. If antibiotics cross bacterial cell envelopes slowly to reach their target, there is a delay in the onset of action that may be reduced by increasing initial antibiotic concentration. Finally, slow drug-target dissociation and slow diffusion out of cells act to prolong antibiotic effects, thereby allowing for less frequent dosing. Our model can be used as a tool in the rational design of treatment for bacterial infections. It is easily adaptable to other biological systems, e.g. HIV, malaria and cancer, where the effects of physiological fluctuations of drug concentration are also poorly understood. PMID:28060813

  11. Using Chemical Reaction Kinetics to Predict Optimal Antibiotic Treatment Strategies.

    PubMed

    Abel Zur Wiesch, Pia; Clarelli, Fabrizio; Cohen, Ted

    2017-01-01

    Identifying optimal dosing of antibiotics has proven challenging-some antibiotics are most effective when they are administered periodically at high doses, while others work best when minimizing concentration fluctuations. Mechanistic explanations for why antibiotics differ in their optimal dosing are lacking, limiting our ability to predict optimal therapy and leading to long and costly experiments. We use mathematical models that describe both bacterial growth and intracellular antibiotic-target binding to investigate the effects of fluctuating antibiotic concentrations on individual bacterial cells and bacterial populations. We show that physicochemical parameters, e.g. the rate of drug transmembrane diffusion and the antibiotic-target complex half-life are sufficient to explain which treatment strategy is most effective. If the drug-target complex dissociates rapidly, the antibiotic must be kept constantly at a concentration that prevents bacterial replication. If antibiotics cross bacterial cell envelopes slowly to reach their target, there is a delay in the onset of action that may be reduced by increasing initial antibiotic concentration. Finally, slow drug-target dissociation and slow diffusion out of cells act to prolong antibiotic effects, thereby allowing for less frequent dosing. Our model can be used as a tool in the rational design of treatment for bacterial infections. It is easily adaptable to other biological systems, e.g. HIV, malaria and cancer, where the effects of physiological fluctuations of drug concentration are also poorly understood.

  12. Comparison of treatment strategies for Space Motion Sickness

    NASA Astrophysics Data System (ADS)

    Davis, J. R.; Jennings, R. T.; Beck, B. G.

    Treatment strategies for Space Motion Sickness (SMS) were compared using the results of postflight oral debriefings. Standardized questionnaires were administered to all crewmembers immediately following Space Shuttle flights by NASA flight surgeons. Cases of SMS were graded as mild, moderate, or severe based on published criteria, and medication effectiveness was judged based on subjective reports of symptom relief. Since October 1989, medication effectiveness is reported inflight through Private Medical Conferences with the crew. A symptom matrix was analyzed for 19 crewmembers treated with oral combination of scopolamine and dextroamphetamine (scopdex) and 15 crewmembers treated with promethazine delivered by intramuscular i.m. or suppository routes. Scopdex has been given preflight as prophylaxis for SMS, but analysis showed delayed symptom presentation in 9 crewmembers or failed to prevent symptoms in 7. Only 3 crewmembers who took scopdex had no symptoms inflight. Fourteen out of 15 crewmembers treated with i.m. promethazine and 6 of 8 treated with promethazine suppositories after symptom development had immediate (within 1-2h) symptom relief and required no additional medication. There were no cases of delayed symptom presentation in the crewmembers treated with promethazine. This response is in contrast to untreated crewmembers who typically have slow symptom resolution over 72-96h. We conclude that promethazine is an effective treatment of SMS symptoms inflight. NASA policy currently recommends treating crewmembers with SMS after symptom development, and no longer recommends prophylaxis with scopdex due to delayed symptom development and apparent variable absorption of oral medications during early flight days.

  13. A review of current treatment strategies for gestational diabetes mellitus

    PubMed Central

    Kelley, Kristi W; Carroll, Dana G; Meyer, Allison

    2015-01-01

    Approximately 90% of diabetes cases in pregnant women are considered gestational diabetes mellitus (GDM). It is well known that uncontrolled glucose results in poor pregnancy outcomes in both the mother and fetus. Worldwide there are many guidelines with recommendations for appropriate management strategies for GDM once lifestyle modifications have been instituted and failed to achieve control. The efficacy and particularly the safety of other treatment modalities for GDM has been the source of much debate in recent years. Studies that have demonstrated the safety and efficacy of both glyburide and metformin in the management of patients with GDM will be reviewed. There is a lack of evidence with other oral and injectable non-insulin agents to control blood glucose in GDM. The role of insulin will be discussed, with emphasis on insulin analogs. Ideal patient characteristics for each treatment modality will be reviewed. In addition, recommendations for postpartum screening of patients will be described as well as recommendations for use of agents to manage subsequent type 2 diabetes in patients who are breastfeeding. PMID:26213555

  14. Future Directions in the Treatment of Gastrointestinal and Pancreatic Neuroendocrine Tumors.

    PubMed

    Asmis, Timothy

    2016-07-01

    Recently, the landscape of the diagnosis and treatment of patients with well-differentiated gastrointestinal/pancreatic neuroendocrine tumors (previously referred to as carcinoid tumors) has changed dramatically. We will need to work with all of the stakeholders including clinicians, patients, regulatory agencies, and industry to best navigate future treatment and research. Future protocols will require us to define clinically relevant end points. In designing future clinical trials, we will need to determine which patients will be included in these studies. Future research will need to address the best way to image and follow patient's disease both in the clinic and on research studies. Timely access to new therapies will be the utmost importance to both current and future patients. We must work together to establish relevant clinical questions and to pursue collaborative research that promotes the health of our patients.

  15. Rabies Control and Treatment: From Prophylaxis to Strategies with Curative Potential

    PubMed Central

    Zhu, Shimao; Guo, Caiping

    2016-01-01

    Rabies is an acute, fatal, neurological disease that affects almost all kinds of mammals. Vaccination (using an inactivated rabies vaccine), combined with administration of rabies immune globulin, is the only approved, effective method for post-exposure prophylaxis against rabies in humans. In the search for novel rabies control and treatment strategies, live-attenuated viruses have recently emerged as a practical and promising approach for immunizing and controlling rabies. Unlike the conventional, inactivated rabies vaccine, live-attenuated viruses are genetically modified viruses that are able to replicate in an inoculated recipient without causing adverse effects, while still eliciting robust and effective immune responses against rabies virus infection. A number of viruses with an intrinsic capacity that could be used as putative candidates for live-attenuated rabies vaccine have been intensively evaluated for therapeutic purposes. Additional novel strategies, such as a monoclonal antibody-based approach, nucleic acid-based vaccines, or small interfering RNAs (siRNAs) interfering with virus replication, could further add to the arena of strategies to combat rabies. In this review, we highlight current advances in rabies therapy and discuss the role that they might have in the future of rabies treatment. Given the pronounced and complex impact of rabies on a patient, a combination of these novel modalities has the potential to achieve maximal anti-rabies efficacy, or may even have promising curative effects in the future. However, several hurdles regarding clinical safety considerations and public awareness should be overcome before these approaches can ultimately become clinically relevant therapies. PMID:27801824

  16. Rabies Control and Treatment: From Prophylaxis to Strategies with Curative Potential.

    PubMed

    Zhu, Shimao; Guo, Caiping

    2016-10-28

    Rabies is an acute, fatal, neurological disease that affects almost all kinds of mammals. Vaccination (using an inactivated rabies vaccine), combined with administration of rabies immune globulin, is the only approved, effective method for post-exposure prophylaxis against rabies in humans. In the search for novel rabies control and treatment strategies, live-attenuated viruses have recently emerged as a practical and promising approach for immunizing and controlling rabies. Unlike the conventional, inactivated rabies vaccine, live-attenuated viruses are genetically modified viruses that are able to replicate in an inoculated recipient without causing adverse effects, while still eliciting robust and effective immune responses against rabies virus infection. A number of viruses with an intrinsic capacity that could be used as putative candidates for live-attenuated rabies vaccine have been intensively evaluated for therapeutic purposes. Additional novel strategies, such as a monoclonal antibody-based approach, nucleic acid-based vaccines, or small interfering RNAs (siRNAs) interfering with virus replication, could further add to the arena of strategies to combat rabies. In this review, we highlight current advances in rabies therapy and discuss the role that they might have in the future of rabies treatment. Given the pronounced and complex impact of rabies on a patient, a combination of these novel modalities has the potential to achieve maximal anti-rabies efficacy, or may even have promising curative effects in the future. However, several hurdles regarding clinical safety considerations and public awareness should be overcome before these approaches can ultimately become clinically relevant therapies.

  17. Application of nitrogen sufficiency conversion strategy for microalgae-based ammonium-rich wastewater treatment.

    PubMed

    Wang, Jinghan; Zhou, Wenguang; Yang, Haizhen; Ruan, Roger

    2016-10-01

    Ammonium ([Formula: see text]-N)-rich wastewater, a main cause for eutrophication, can serve as a promising medium for fast microalgae cultivation with efficient [Formula: see text]-N removal. To achieve this goal, a well-controlled three-stage treatment process was developed. Two trophic modes (mixotrophy and heterotrophy) in Stage 1 and Stage 2, with two nitrogen availability conditions (N sufficient and N deprived) in Stage 2, and different [Formula: see text]-N concentrations in Stage 3 were compared to investigate the effects of nitrogen sufficiency conversion on indigenous strain UMN266 for [Formula: see text]-N removal. Results showed that mixotrophic cultures in the first two stages with N deprivation in Stage 2 was the optimum treatment strategy, and higher [Formula: see text]-N concentration in Stage 3 facilitated both microalgal growth and [Formula: see text]-N removal, with average and maximum biomass productivity of 55.3 and 161.0 mg L(-1) d(-1), and corresponding removal rates of 4.2 and 15.0 mg L(-1) d(-1), respectively, superior to previously published results. Observations of intracellular compositions confirmed the optimum treatment strategy, discovering excellent starch accumulating property of strain UMN266 as well. Combination of bioethanol production with the proposed three-stage process using various real wastewater streams at corresponding stages was suggested for future application.

  18. Current and emerging treatment strategies for Duchenne muscular dystrophy

    PubMed Central

    Mah, Jean K

    2016-01-01

    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

  19. Device-Aided Treatment Strategies in Advanced Parkinson's Disease.

    PubMed

    Timpka, Jonathan; Nitu, Bianca; Datieva, Veronika; Odin, Per; Antonini, Angelo

    2017-01-01

    With peroral levodopa treatment, a majority of patients develop motor fluctuations and dyskinesia already within a few years of therapy. Device-aided Parkinson (PD) therapies refer to deep brain stimulation (DBS), levodopa-carbidopa intestinal gel infusion (LCIG), and subcutaneous infusion of the dopamine agonist apomorphine and represent effective strategies counteracting motor fluctuations and dyskinesia. These three therapy options seem to be similarly effective in reducing "time with PD symptoms (off time)" by at least 60%-65%. The use of advanced therapy also leads to a significant reduction of dyskinesia. Recent studies also indicate that these therapies can improve a number of nonmotor symptoms in advanced PD. Altogether this results in an improved health-related quality of life in most treated patients. The side effects and complications are quite different between the three; for DBS, serious adverse events include intracranial bleeding and infection, LCIG complications relate to the infusion equipment and the establishment of the percutaneous endoscopic gastrostomy, while for apomorphine infusion the most common side effect is a formation of noduli (local inflammation) at the point of infusion. The device-aided therapies are all indicated for the treatment of motor fluctuations and/or dyskinesia when peroral/transdermal PD medications cannot be further optimized. However, the choice of device-aided therapy is made on basis of indications/contraindications, but also the patients' symptom profile and his/her personal preferences. Therefore, it is important these treatments are discussed early, well before motor and nonmotor symptoms have deteriorated excessively. © 2017 Elsevier Inc. All rights reserved.

  20. Coronary microvascular dysfunction, microvascular angina, and treatment strategies.

    PubMed

    Marinescu, Mark A; Löffler, Adrián I; Ouellette, Michelle; Smith, Lavone; Kramer, Christopher M; Bourque, Jamieson M

    2015-02-01

    Angina without coronary artery disease (CAD) has substantial morbidity and is present in 10% to 30% of patients undergoing angiography. Coronary microvascular dysfunction (CMD) is present in 50% to 65% of these patients. The optimal treatment of this cohort is undefined. We performed a systematic review to evaluate treatment strategies for objectively-defined CMD in the absence of CAD. We included studies assessing therapy in human subjects with angina and coronary flow reserve or myocardial perfusion reserve <2.5 by positron emission tomography, cardiac magnetic resonance imaging, dilution methods, or intracoronary Doppler in the absence of coronary artery stenosis ≥50% or structural heart disease. Only 8 papers met the strict inclusion criteria. The papers were heterogeneous, using different treatments, endpoints, and definitions of CMD. The small sample sizes severely limit the power of these studies, with an average of 11 patients per analysis. Studies evaluating sildenafil, quinapril, estrogen, and transcutaneous electrical nerve stimulation application demonstrated benefits in their respective endpoints. No benefit was found with L-arginine, doxazosin, pravastatin, and diltiazem. Our systematic review highlights that there is little data to support therapies for CMD. We assess the data meeting rigorous inclusion criteria and review the related but excluded published data. We additionally describe the next steps needed to address this research gap, including a standardized definition of CMD, routine assessment of CMD in studies of chest pain without obstructive CAD, and specific therapy assessment in the population with confirmed CMD. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.