20 CFR 404.527 - Additional methods for recovery of title II benefit overpayments.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Additional methods for recovery of title II... or Recovery of Overpayments, and Liability of a Certifying Officer § 404.527 Additional methods for recovery of title II benefit overpayments. (a) General. In addition to the methods specified in §§ 404.502...

20 CFR 404.527 - Additional methods for recovery of title II benefit overpayments.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Additional methods for recovery of title II... or Recovery of Overpayments, and Liability of a Certifying Officer § 404.527 Additional methods for recovery of title II benefit overpayments. (a) General. In addition to the methods specified in §§ 404.502...

20 CFR 404.527 - Additional methods for recovery of title II benefit overpayments.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Additional methods for recovery of title II... or Recovery of Overpayments, and Liability of a Certifying Officer § 404.527 Additional methods for recovery of title II benefit overpayments. (a) General. In addition to the methods specified in §§ 404.502...

20 CFR 404.527 - Additional methods for recovery of title II benefit overpayments.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Additional methods for recovery of title II... or Recovery of Overpayments, and Liability of a Certifying Officer § 404.527 Additional methods for recovery of title II benefit overpayments. (a) General. In addition to the methods specified in §§ 404.502...

Benefit-Risk Assessment, Communication, and Evaluation (BRACE) throughout the life cycle of therapeutic products: overall perspective and role of the pharmacoepidemiologist.

PubMed

Radawski, Christine; Morrato, Elaine; Hornbuckle, Kenneth; Bahri, Priya; Smith, Meredith; Juhaeri, Juhaeri; Mol, Peter; Levitan, Bennett; Huang, Han-Yao; Coplan, Paul; Li, Hu

2015-12-01

Optimizing a therapeutic product's benefit-risk profile is an on-going process throughout the product's life cycle. Different, yet related, benefit-risk assessment strategies and frameworks are being developed by various regulatory agencies, industry groups, and stakeholders. This paper summarizes current best practices and discusses the role of the pharmacoepidemiologist in these activities, taking a life-cycle approach to integrated Benefit-Risk Assessment, Communication, and Evaluation (BRACE). A review of the medical and regulatory literature was performed for the following steps involved in therapeutic benefit-risk optimization: benefit-risk evidence generation; data integration and analysis; decision making; regulatory and policy decision making; benefit-risk communication and risk minimization; and evaluation. Feedback from International Society for Pharmacoepidemiology members was solicited on the role of the pharmacoepidemiologist. The case example of natalizumab is provided to illustrate the cyclic nature of the benefit-risk optimization process. No single, globally adopted benefit-risk assessment process exists. The BRACE heuristic offers a way to clarify research needs and to promote best practices in a cyclic and integrated manner and highlight the critical importance of cross-disciplinary input. Its approach focuses on the integration of BRACE activities for risk minimization and optimization of the benefit-risk profile. The activities defined in the BRACE heuristic contribute to the optimization of the benefit-risk profile of therapeutic products in the clinical world at both the patient and population health level. With interdisciplinary collaboration, pharmacoepidemiologists are well suited for bringing in methodology expertise, relevant research, and public health perspectives into the BRACE process. Copyright © 2015 John Wiley & Sons, Ltd.

A Qualitative Study of the Perceived Health Benefits of a Therapeutic Riding Program for Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Stickney, Margaret Ann

2010-01-01

Therapeutic horseback riding can be recommended as a useful health promotion intervention for individuals with disabilities who face challenges to optimal health and wellness. This qualitative study examined the perceived benefits of a therapeutic riding program for children with autism spectrum disorders (ASD), with particular focus on aspects…

Breastfeeding peer support: are there additional benefits?

PubMed

Wade, Deborah; Haining, Shona; Day, Ann

2009-12-01

Anecdotal discussion among breastfeeding peer supporters and the infant-feeding co-ordinator suggested that breastfeeding peer support provided by breastfeeding peer supporters may offer benefits to breastfeeding women and their families other than increasing breastfeeding initiation and sustainability. The aim of this research was to determine whether there was evidence to support this. The research team used focus groups to obtain information from 16 local women who had received breastfeeding peer support from breastfeeding peer supporters. The key themes that emerged were--improved mental health, increased self-esteem or confidence, parenting skills, improved family diet, breastfeeding sustainability and poor hospital experience.The findings suggest that breastfeeding peer supporters supporting mothers to breastfeed, with the intention of increasing both breastfeeding rates and sustainability, may have additional benefits in several aspects of families' lives. Breastfeeding peer support may play an important role in helping to attain targets such as reducing obesity and postnatal depression.

20 CFR 416.590 - Are there additional methods for recovery of title XVI benefit overpayments?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Are there additional methods for recovery of title XVI benefit overpayments? 416.590 Section 416.590 Employees' Benefits SOCIAL SECURITY..., and Underpayments § 416.590 Are there additional methods for recovery of title XVI benefit...

20 CFR 416.590 - Are there additional methods for recovery of title XVI benefit overpayments?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Are there additional methods for recovery of title XVI benefit overpayments? 416.590 Section 416.590 Employees' Benefits SOCIAL SECURITY..., and Underpayments § 416.590 Are there additional methods for recovery of title XVI benefit...

20 CFR 416.590 - Are there additional methods for recovery of title XVI benefit overpayments?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Are there additional methods for recovery of title XVI benefit overpayments? 416.590 Section 416.590 Employees' Benefits SOCIAL SECURITY..., and Underpayments § 416.590 Are there additional methods for recovery of title XVI benefit...

20 CFR 416.590 - Are there additional methods for recovery of title XVI benefit overpayments?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Are there additional methods for recovery of title XVI benefit overpayments? 416.590 Section 416.590 Employees' Benefits SOCIAL SECURITY..., and Underpayments § 416.590 Are there additional methods for recovery of title XVI benefit...

Stem cell transplantation therapy for multifaceted therapeutic benefits after stroke.

PubMed

Wei, Ling; Wei, Zheng Z; Jiang, Michael Qize; Mohamad, Osama; Yu, Shan Ping

2017-10-01

One of the exciting advances in modern medicine and life science is cell-based neurovascular regeneration of damaged brain tissues and repair of neuronal structures. The progress in stem cell biology and creation of adult induced pluripotent stem (iPS) cells has significantly improved basic and pre-clinical research in disease mechanisms and generated enthusiasm for potential applications in the treatment of central nervous system (CNS) diseases including stroke. Endogenous neural stem cells and cultured stem cells are capable of self-renewal and give rise to virtually all types of cells essential for the makeup of neuronal structures. Meanwhile, stem cells and neural progenitor cells are well-known for their potential for trophic support after transplantation into the ischemic brain. Thus, stem cell-based therapies provide an attractive future for protecting and repairing damaged brain tissues after injury and in various disease states. Moreover, basic research on naïve and differentiated stem cells including iPS cells has markedly improved our understanding of cellular and molecular mechanisms of neurological disorders, and provides a platform for the discovery of novel drug targets. The latest advances indicate that combinatorial approaches using cell based therapy with additional treatments such as protective reagents, preconditioning strategies and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the characteristics of cell therapy in different ischemic models and the application of stem cells and progenitor cells as regenerative medicine for the treatment of stroke. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multifaceted Therapeutic Benefits of Factors Derived From Dental Pulp Stem Cells for Mouse Liver Fibrosis.

PubMed

Hirata, Marina; Ishigami, Masatoshi; Matsushita, Yoshihiro; Ito, Takanori; Hattori, Hisashi; Hibi, Hideharu; Goto, Hidemi; Ueda, Minoru; Yamamoto, Akihito

2016-10-01

: Chronic liver injury from various causes often results in liver fibrosis (LF). Although the liver possesses endogenous tissue-repairing activities, these can be overcome by sustained inflammation and excessive fibrotic scar formation. Advanced LF leads to irreversible cirrhosis and subsequent liver failure and/or hepatic cancer. Here, using the mouse carbon tetrachloride (CCl 4 )-induced LF model, we showed that a single intravenous administration of stem cells derived from human exfoliated deciduous teeth (SHEDs) or of SHED-derived serum-free conditioned medium (SHED-CM) resulted in fibrotic scar resolution. SHED-CM suppressed the gene expression of proinflammatory mediators, such as TNF-α, IL-1β, and iNOS, and eliminated activated hepatic stellate cells by inducing their apoptosis, but protected parenchymal hepatocytes from undergoing apoptosis. In addition, SHED-CM induced tissue-repairing macrophages that expressed high levels of the profibrinolytic factor, matrix metalloproteinase 13. Furthermore, SHED-CM suppressed the CCl 4 -induced apoptosis of primary cultured hepatocytes. SHED-CM contained a high level of hepatocyte growth factor (HGF). Notably, HGF-depleted SHED-CM (dHGF-CM) did not suppress the proinflammatory response or resolve fibrotic scarring. Furthermore, SHED-CM, but not dHGF-CM, inhibited CCl 4 -induced hepatocyte apoptosis. These results suggest that HGF plays a central role in the SHED-CM-mediated resolution of LF. Taken together, our findings suggest that SHED-CM provides multifaceted therapeutic benefits for the treatment of LF. This study demonstrated that a single intravenous administration of stem cells from human exfoliated deciduous teeth (SHEDs) or of the serum-free conditioned medium (CM) derived from SHEDs markedly improved mouse liver fibrosis (LF). SHED-CM suppressed chronic inflammation, eliminated activated hepatic stellate cells by inducing their apoptosis, protected hepatocytes from undergoing apoptosis, and induced

Costs, Benefits, and Adoption of Additive Manufacturing: A Supply Chain Perspective.

PubMed

Thomas, Douglas

2016-07-01

There are three primary aspects to the economics of additive manufacturing: measuring the value of goods produced, measuring the costs and benefits of using the technology, and estimating the adoption and diffusion of the technology. This paper provides an updated estimate of the value of goods produced. It then reviews the literature on additive manufacturing costs and identifies those instances in the literature where this technology is cost effective. The paper then goes on to propose an approach for examining and understanding the societal costs and benefits of this technology both from a monetary viewpoint and a resource consumption viewpoint. The final section discusses the trends in the adoption of additive manufacturing. Globally, there is an estimated $667 million in value added produced using additive manufacturing, which equates to 0.01 % of total global manufacturing value added. US value added is estimated as $241 million. Current research on additive manufacturing costs reveals that it is cost effective for manufacturing small batches with continued centralized production; however, with increased automation distributed production may become cost effective. Due to the complexities of measuring additive manufacturing costs and data limitations, current studies are limited in their scope. Many of the current studies examine the production of single parts and those that examine assemblies tend not to examine supply chain effects such as inventory and transportation costs along with decreased risk to supply disruption. The additive manufacturing system and the material costs constitute a significant portion of an additive manufactured product; however, these costs are declining over time. The current trends in costs and benefits have resulted in this technology representing 0.02 % of the relevant manufacturing industries in the US; however, as the costs of additive manufacturing systems decrease, this technology may become widely adopted and change the

Costs, Benefits, and Adoption of Additive Manufacturing: A Supply Chain Perspective

PubMed Central

Thomas, Douglas

2017-01-01

There are three primary aspects to the economics of additive manufacturing: measuring the value of goods produced, measuring the costs and benefits of using the technology, and estimating the adoption and diffusion of the technology. This paper provides an updated estimate of the value of goods produced. It then reviews the literature on additive manufacturing costs and identifies those instances in the literature where this technology is cost effective. The paper then goes on to propose an approach for examining and understanding the societal costs and benefits of this technology both from a monetary viewpoint and a resource consumption viewpoint. The final section discusses the trends in the adoption of additive manufacturing. Globally, there is an estimated $667 million in value added produced using additive manufacturing, which equates to 0.01 % of total global manufacturing value added. US value added is estimated as $241 million. Current research on additive manufacturing costs reveals that it is cost effective for manufacturing small batches with continued centralized production; however, with increased automation distributed production may become cost effective. Due to the complexities of measuring additive manufacturing costs and data limitations, current studies are limited in their scope. Many of the current studies examine the production of single parts and those that examine assemblies tend not to examine supply chain effects such as inventory and transportation costs along with decreased risk to supply disruption. The additive manufacturing system and the material costs constitute a significant portion of an additive manufactured product; however, these costs are declining over time. The current trends in costs and benefits have resulted in this technology representing 0.02 % of the relevant manufacturing industries in the US; however, as the costs of additive manufacturing systems decrease, this technology may become widely adopted and change the

Karaoke for quads: a new application of an old recreation with potential therapeutic benefits for people with disabilities.

PubMed

Batavia, A I; Batavia, M

2003-03-18

Karaoke is a recreational activity whereby individuals sing into a microphone along with the melodies and lyrics provided both visually and auditorily by a machine. The potential therapeutic benefits of karaoke are explored in terms of increased respiratory strength, endurance, control, and capacity, as well as emotional and physical release for people with disabilities. Although many individuals with disabilities could benefit from this activity, it is likely to be particularly beneficial to people with compromised respiratory systems, such as persons with high-level quadriplegia (tetraplegia). This article examines theoretical considerations and proposes a research agenda. Empirical research would be valuable to confirm the potential benefits of karaoke for people with disabilities.

Additive Benefits of Twice Forest Bathing Trips in Elderly Patients with Chronic Heart Failure.

PubMed

Mao, Gen Xiang; Cao, Yong Bao; Yang, Yan; Chen, Zhuo Mei; Dong, Jian Hua; Chen, Sha Sha; Wu, Qing; Lyu, Xiao Ling; Jia, Bing Bing; Yan, Jing; Wang, Guo Fu

2018-02-01

Chronic heart failure (CHF), a clinical syndrome resulting from the consequences of various cardiovascular diseases (CVDs), is increasingly becoming a global cause of morbidity and mortality. We had earlier demonstrated that a 4-day forest bathing trip can provide an adjunctive therapeutic influence on patients with CHF. To further investigate the duration of the impact and the optimal frequency of forest bathing trips in patients with CHF, we recruited those subjects who had experienced the first forest bathing trip again after 4 weeks and randomly categorized them into two groups, namely, the urban control group (city) and the forest bathing group (forest). After a second 4-day forest bathing trip, we observed a steady decline in the brain natriuretic peptide levels, a biomarker of heart failure, and an attenuated inflammatory response as well as oxidative stress. Thus, this exploratory study demonstrated the additive benefits of twice forest bathing trips in elderly patients with CHF, which could further pave the way for analyzing the effects of such interventions in CVDs. Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

The therapeutic benefits of gravity in space and on earth.

PubMed

Kourtidou-Papadeli, C; Papadelis, C L; Vernikos, J; Bamidis, P D; Hitoglou-Antoniadou, M; Perantoni, E; Vlachogiannis, E

2008-08-01

The traditional scientific approach of investigating the role of a variable on a living organism is to remove it or the ability of the organism to sense it. Gravity is no exception. Access to space has made it possible for us to begin the exploration of how gravity has influenced our evolution, our genetic make-up and our physiology. Identifying the thresholds at which each body system perceives, how much, how often, how long the gravity stimulus is needed and in which direction should it be presented for maximum effectiveness, is fundamental knowledge required for using artificial gravity as a therapeutic or maintenance countermeasure treatment in exploration missions. Here on earth, although surrounded by gravity we are negligent in using gravity as it was intended, to maintain the level of health that is appropriate to living in 1G. These, changes in lifestyle or pathologies caused by various types of injury can benefit as well from artificial gravity in much the same way as we are now considering for astronauts in space.

20 CFR 30.912 - Can a covered Part E employee receive benefits for additional impairment following an award of...

Code of Federal Regulations, 2010 CFR

2010-04-01

... benefits for additional impairment following an award of such benefits by OWCP? 30.912 Section 30.912... OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000, AS AMENDED Impairment Benefits Under Part E of EEOICPA Ratable Impairments § 30.912 Can a covered Part E employee receive benefits for additional impairment...

20 CFR 10.332 - What additional medical information will OWCP require to support continuing payment of benefits?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false What additional medical information will OWCP require to support continuing payment of benefits? 10.332 Section 10.332 Employees' Benefits OFFICE OF... COMPENSATION UNDER THE FEDERAL EMPLOYEES' COMPENSATION ACT, AS AMENDED Medical and Related Benefits Medical...

20 CFR 408.808 - What happens to your SVB payments if you begin receiving additional benefit income?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false What happens to your SVB payments if you begin receiving additional benefit income? 408.808 Section 408.808 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Suspensions and Terminations Suspension § 408...

20 CFR 408.808 - What happens to your SVB payments if you begin receiving additional benefit income?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false What happens to your SVB payments if you begin receiving additional benefit income? 408.808 Section 408.808 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Suspensions and Terminations Suspension § 408...

20 CFR 408.808 - What happens to your SVB payments if you begin receiving additional benefit income?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What happens to your SVB payments if you begin receiving additional benefit income? 408.808 Section 408.808 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Suspensions and Terminations Suspension § 408...

20 CFR 408.808 - What happens to your SVB payments if you begin receiving additional benefit income?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false What happens to your SVB payments if you begin receiving additional benefit income? 408.808 Section 408.808 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Suspensions and Terminations Suspension § 408...

20 CFR 408.808 - What happens to your SVB payments if you begin receiving additional benefit income?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false What happens to your SVB payments if you begin receiving additional benefit income? 408.808 Section 408.808 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Suspensions and Terminations Suspension § 408...

Melatonin: Pharmacology, Functions and Therapeutic Benefits

PubMed Central

Tordjman, Sylvie; Chokron, Sylvie; Delorme, Richard; Charrier, Annaëlle; Bellissant, Eric; Jaafari, Nemat; Fougerou, Claire

2017-01-01

Abstract: Background: Melatonin synchronizes central but also peripheral oscillators (fetal adrenal gland, pancreas, liver, kidney, heart, lung, fat, gut, etc.), allowing temporal organization of biological functions through circadian rhythms (24-hour cycles) in relation to periodic environmental changes and therefore adaptation of the individual to his/her internal and external environment. Measures of melatonin are considered the best peripheral indices of human circadian timing based on an internal 24-hour clock. Methods: First, the pharmacology of melatonin (biosynthesis and circadian rhythms, pharmacokinetics and mechanisms of action) is described, allowing a better understanding of the short and long term effects of melatonin following its immediate or prolonged release. Then, research related to the physiological effects of melatonin is reviewed. Results: The physiological effects of melatonin are various and include detoxification of free radicals and antioxidant actions, bone formation and protection, reproduction, and cardiovascular, immune or body mass regulation. Also, protective and therapeutic effects of melatonin are reported, especially with regard to brain or gastrointestinal protection, psychiatric disorders, cardiovascular diseases and oncostatic effects. Conclusion: This review highlights the high number and diversity of major melatonin effects and opens important perspectives for measuring melatonin as a biomarker (biomarker of early identification of certain disorders and also biomarker of their follow-up) and using melatonin with clinical preventive and therapeutic applications in newborns, children and adults based on its physiological regulatory effects. PMID:28503116

Evaluation of Therapeutics for Advanced-Stage Heart Failure and Other Severely-Debilitating or Life-Threatening Diseases.

PubMed

Prescott, J S; Andrews, P A; Baker, R W; Bogdanffy, M S; Fields, F O; Keller, D A; Lapadula, D M; Mahoney, N M; Paul, D E; Platz, S J; Reese, D M; Stoch, S A; DeGeorge, J J

2017-08-01

Severely-debilitating or life-threatening (SDLT) diseases include conditions in which life expectancy is short or quality of life is greatly diminished despite available therapies. As such, the medical context for SDLT diseases is comparable to advanced cancer and the benefit vs. risk assessment and development of SDLT disease therapeutics should be similar to that of advanced cancer therapeutics. A streamlined development approach would allow patients with SDLT conditions earlier access to therapeutics and increase the speed of progression through development. In addition, this will likely increase the SDLT disease therapeutic pipeline, directly benefiting patients and reducing the economic and societal burden of SDLT conditions. Using advanced-stage heart failure (HF) as an example that illustrates the concepts applicable to other SDLT indications, this article proposes a streamlined development paradigm for SDLT disease therapeutics and recommends development of aligned global regulatory guidance. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Therapeutic Benefit of Smoked Cannabis in Randomized Placebo-Controlled Studies.

PubMed

Bowen, Lynneice L; McRae-Clark, Aimee L

2018-01-01

The medicinal use of marijuana has been legalized in 28 states, with a wide range of specificity for approved medical conditions. Even with the emergence of non-combustion-based delivery systems, 90% of marijuana users in 2014 used smoked marijuana. This review summarizes the data available on the use of smoked marijuana for medical purposes. A literature search was performed to retrieve randomized controlled trials exploring the efficacy of smoked cannabis for treatment of a medical condition. Studies with the primary end point listed as the effect of smoked cannabis on a disease-specific characteristic were included. Open-label studies and studies using other administration methods were excluded. Seven studies met these criteria and were included in this review. Cannabis did not outperform placebo on experimentally evoked pain or the timed walk test. Clear evidence indicates that smoked cannabis reduces intraocular pressure, but the effect is too brief (less than 4 hrs) to be of therapeutic benefit for this chronic disorder. Consistent evidence also showed that smoked marijuana, even at lower concentrations of tetrahydrocannabinol, increased total daily calorie intake and number of eating occasions. Neither of the studies with quality of life as secondary outcome measures revealed statistically significantly improved outcomes with cannabis use. © 2017 Pharmacotherapy Publications, Inc.

Study on the Therapeutic Benefit on Lactoferrin in Patients with Colorectal Cancer Receiving Chemotherapy

PubMed Central

Moastafa, Tarek M.; El-Sissy, Alaa El-Din Elsayed; El-Saeed, Gehan K.; Koura, Mai Salah El-Din

2014-01-01

A double-blinded parallel randomized controlled clinical trial was conducted on two groups of colorectal cancer patients to study the therapeutic benefit of orally administered bovine lactoferrin (bLF) on colorectal cancer patients having age ranges from 20 to 71 years and who received 5-fluorouracil and leucovorin calcium. Test group (15 patients) received oral bLF 250 mg/day beside chemotherapy for three months. Control group (15 patients) received chemotherapy only. Serum lactoferrin (LF), serum glutathione-s-transferase enzyme (GST), interferon gamma (INF-γ), tumor marker carcinoembryonic antigen (CEA), renal function tests, hepatic function tests, and complete blood count were measured for both groups before and at the end of the trial. Although, there was a significant effect of oral bLF (250 mg/day) that indicated a significant improvement in mean percent of change of all parameters 3 months after treatment, there was no significant difference between results of patients in the test group and patients in the control group after treatment. This result suggests that oral bLF has significant therapeutic effect on colorectal cancer patients. Our study suggests that daily administration of bLF showed a clinically beneficial effect to colorectal cancer patients with better disease prognosis but that needs further looking into. PMID:27350986

Study on the Therapeutic Benefit on Lactoferrin in Patients with Colorectal Cancer Receiving Chemotherapy.

PubMed

Moastafa, Tarek M; El-Sissy, Alaa El-Din Elsayed; El-Saeed, Gehan K; Koura, Mai Salah El-Din

2014-01-01

A double-blinded parallel randomized controlled clinical trial was conducted on two groups of colorectal cancer patients to study the therapeutic benefit of orally administered bovine lactoferrin (bLF) on colorectal cancer patients having age ranges from 20 to 71 years and who received 5-fluorouracil and leucovorin calcium. Test group (15 patients) received oral bLF 250 mg/day beside chemotherapy for three months. Control group (15 patients) received chemotherapy only. Serum lactoferrin (LF), serum glutathione-s-transferase enzyme (GST), interferon gamma (INF-γ), tumor marker carcinoembryonic antigen (CEA), renal function tests, hepatic function tests, and complete blood count were measured for both groups before and at the end of the trial. Although, there was a significant effect of oral bLF (250 mg/day) that indicated a significant improvement in mean percent of change of all parameters 3 months after treatment, there was no significant difference between results of patients in the test group and patients in the control group after treatment. This result suggests that oral bLF has significant therapeutic effect on colorectal cancer patients. Our study suggests that daily administration of bLF showed a clinically beneficial effect to colorectal cancer patients with better disease prognosis but that needs further looking into.

[Involvement of scientific societies in early benefit assessment: Simulated participation or valuable additional input?

PubMed

Bleß, Hans-Holger; Seidlitz, Cornelia; Ohlmeier, Christoph; de Millas, Christoph

2018-02-01

The German framework of early benefit assessment (EBA) of drugs also provides for the participation of scientific medical societies. The aim of their inclusion is to assure that care providers can critically assess all aspects of the EBA and provide insights into relevant aspects regarding the provision of care. This study systematically reviews the frequency of participation of the scientific medical societies (FGs) and the Drug Commission of the German Medical Association (AkdÄ) within the scope of the EBA. In addition, the positioning of AkdÄ/FG is compared to the Institute for Quality and Efficiency in Health Care (IQWiG) and the Federal Joint Committee (G-BA) with a focus on antidiabetic drugs and cancer drugs. A literature analysis was performed based on the comprehensive documentation of benefit assessments published by G-BA. All proceedings of antidiabetic drugs and cancer drugs were included, for which a decision was published by August 6, 2015. In addition, statements of FGs or AkdÄ were identified by an exploratory literature review and included in the analysis. The statements considered were assessed with regard to three categories: (1) additional benefit, (2) appropriate comparator (ZVT) and (3) suitability of the endpoints. For each procedure and category, it was assessed whether there was agreement or disagreement between IGWiG/G-BA and AkdÄ/FGs statements. Regarding the additional benefit, a deviating position was further differentiated according to the level of additional benefit (higher/lower). Afterwards, the proportion of favorable and unfavorable positions was calculated, stratified by FGs and AkdÄ and, separately, for proceedings of antidiabetics and cancer drugs. The literature review revealed 41 proceedings of cancer drugs and 21 proceedings of antidiabetic drugs which were included in the analyses. Statements by AkdÄ/FGs were identified in 90 % of the proceedings for antidiabetic drugs and in 98 % of the proceedings for cancer drugs

Therapeutic Engagement as a Predictor of Retention in Adolescent Therapeutic Community Treatment

ERIC Educational Resources Information Center

Abdel-Salam, Sami; Gunter, Whitney D.

2014-01-01

The adolescent drug problem places a huge toll on society and a heavy burden on the criminal justice system. Research regarding the benefits of therapeutic community (TC) treatment for adolescents has shown it to be effective. Despite the ability of therapeutic communities to lower drug relapse and reduce criminality, a great deal remains unknown…

Therapeutic Mastoidectomy in the Management of Noncholesteatomatous Chronic Otitis Media: Literature Review and Cost Analysis.

PubMed

Trinidade, Aaron; Page, Joshua C; Dornhoffer, John L

2016-12-01

Despite evidence that therapeutic mastoidectomy does not improve outcomes in noncholesteatomatous chronic otitis media, it remains widely performed. An up-to-date systematic review is undertaken and conclusions drawn regarding the best evidence-based practice of its management. PubMed, Google Scholar, Medline Embase, Cochrane, and Web of Science. A combination of the following words was used: chronic otitis media, chronic suppurative otitis media, COM, CSOM, mastoidectomy, tympanoplasty, atelectasis, retraction, tympanic perforation, and therapeutic. From 1742 studies, 7 were selected for full analysis with respect to the benefit of mastoidectomy in the management of active and inactive mucosal chronic otitis media. Most were retrospective studies, with 1 prospective randomized controlled trial available. Overall, there was no evidence to support routine mastoidectomy in conjunction with tympanoplasty in chronic otitis media. For ears with sclerotic mastoids, the evidence suggested that there may be some benefit as a staged procedure. Two studies were analyzed for the benefit of mastoidectomy in addition to tympanoplasty for the management of the atelectatic ear (inactive squamous chronic otitis media). The conclusion was also that mastoidectomy added no benefit. Examination of the available literature supports the notion that therapeutic mastoidectomy does not lend any additional benefit to the management of noncholesteatomatous chronic otitis media. This has implications for patient care, both clinically and financially. Further research, ideally in the form of a prospective, multi-institutional, geographically wide, ethnically diverse, randomized controlled trial, is needed to further support this notion. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Risks, benefits, complications and harms: neglected factors in the current debate on non-therapeutic circumcision.

PubMed

Darby, Robert

2015-03-01

Much of the contemporary debate about the propriety of non-therapeutic circumcision of male infants and boys revolves around the question of risks vs. With its headline conclusion that the benefits outweigh the risks, the current circumcision policy of the American Academy of Pediatrics [AAP] (released 2012) is a typical instance of this line of thought. Since the AAP states that it cannot assess the true incidence of complications, however, critics have pointed out that this conclusion is unwarranted. In this paper it is argued that the AAP's conclusion is untenable not only for empirical reasons related to lack of data, but also for logical and conceptual reasons: the concept of risk employed-risk of surgical complications-is too narrow to be useful in the circumcision debate. Complications are not the only harms of circumcision: the AAP and other parties debating the pros and cons of circumcision should conceptualize their analysis more broadly as risk of harm vs. prospect of benefit, thereby factoring in the value of the foreskin to the individual and the physical and ethical harms of removing it from a non-consenting child.

Neurosteroids in Schizophrenia: Pathogenic and Therapeutic Implications

PubMed Central

Cai, HuaLin; Cao, Ting; Zhou, Xiang; Yao, Jeffrey K.

2018-01-01

Neurosteroids are a group of important endogenous molecules affecting many neural functions in the brain. Increasing evidence suggests a possible role of these neurosteroids in the pathology and symptomatology of schizophrenia (SZ) and other mental disorders. The aim of this review is to summarize the current knowledge about the neural functions of neurosteroids in the brain, and to evaluate the role of the key neurosteroids as candidate modulators in the etiology and therapeutics of SZ. The present paper provides a brief introduction of neurosteroid metabolism and distribution, followed by a discussion of the mechanisms underlying neurosteroid actions in the brain. The content regarding the modulation of the GABAA receptor is elaborated, given the considerable knowledge of its interactions with other neurotransmitter and neuroprotective systems, as well as its ameliorating effects on stress that may play a role in the SZ pathophysiology. In addition, several preclinical and clinical studies suggested a therapeutic benefit of neurosteroids in SZ patients, even though the presence of altered neurosteroid pathways in the circulating blood and/or brain remains debatable. Following treatment of antipsychotic drugs in SZ, therapeutic benefits have also been linked to the regulation of neurosteroid signaling. Specifically, the neurosteroids such as pregnenolone and dehydroepiandrosterone affect a broad spectrum of behavioral functions through their unique molecular characteristics and may represent innovative therapeutic targets for SZ. Future investigations in larger cohorts with long-term follow-ups will be required to ascertain the neuropsychopharmacological role of this yet unexploited class of neurosteroid agents. PMID:29568275

Therapeutic benefit of Salmonella attributed to LPS and TNF-α is exhaustible and dictated by tumor susceptibility

PubMed Central

Kocijancic, Dino; Leschner, Sara; Felgner, Sebastian; Komoll, Ronja-Melinda; Frahm, Michael; Pawar, Vinay; Weiss, Siegfried

2017-01-01

The potential of bacteria-mediated tumor therapy (BMTT) is highlighted by more than a century of investigation. Attenuated Salmonella has prevailed as promising therapeutic agents. For BMTT - categorized as an immune therapy - the exact contribution of particular immune reactions to the therapeutic effect remains ambiguous. In addition, one could argue for or against the requirement of bacterial viability and tumor targeting. Herein we evaluate the isolated therapeutic efficacy of purified LPS and TNF-α, which together account for a dominant immunogenic pathway of gram negative bacteria like Salmonella. We show that therapeutic efficacy against CT26 tumors does not require bacterial viability. Analogous to viable Salmonella SL7207, tumor regression by a specific CD8+ T cell response can be induced by purified LPS or recombinant TNF-α (rTNF-α). Conversely, therapeutic effects against RenCa tumors were abrogated upon bacterial avitalization and limited using isolated adjuvants. This argues for an alternative mechanistic explanation for SL7207 against RenCa that depends on viability and persistence. Unable to boost bacterial therapies by co-injection of rTNF-α suggested therapeutic effects along this axis are exhausted by the intrinsic adjuvanticity of bacteria alone. However, the importance of TNF-α for BMTT was highlighted by its support of tumor invasion and colonization in concert with lower infective doses of Salmonella. In consideration, bacterial therapeutic effectiveness along the axis of LPS and TNF-α appears limited, and does not offer the necessary plasticity for different tumors. This emphasizes a need for recombinant strengthening and vehicular exploitation to accommodate potency, plasticity and distinctiveness in BMTT. PMID:28445131

Dispositional Optimism and Therapeutic Expectations in Early Phase Oncology Trials

PubMed Central

Jansen, Lynn A.; Mahadevan, Daruka; Appelbaum, Paul S.; Klein, William MP; Weinstein, Neil D.; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P.

2016-01-01

Purpose Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early phase oncology trials. Optimism, however, is not a unitary construct – it can also be defined as a general disposition, or what is called dispositional optimism. We assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. We also assessed how dispositional optimism related to unrealistic optimism. Methods Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Results Dispositional optimism was significantly associated with higher expectations for personal therapeutic benefit (Spearman r=0.333, p<0.0001), but was not associated with the therapeutic misconception. (Spearman r=−0.075, p=0.329). Dispositional optimism was weakly associated with unrealistic optimism (Spearman r=0.215, p=0.005). In multivariate analysis, both dispositional optimism (p=0.02) and unrealistic optimism (p<0.0001) were independently associated with high expectations for personal therapeutic benefit. Unrealistic optimism (p=.0001), but not dispositional optimism, was independently associated with the therapeutic misconception. Conclusion High expectations for therapeutic benefit among patient-subjects in early phase oncology trials should not be assumed to result from misunderstanding of specific information about the trials. Our data reveal that these expectations are associated with either a dispositionally positive outlook on life or biased expectations about specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early phase oncology research. PMID:26882017

Ethical Perspectives on RNA Interference Therapeutics

PubMed Central

Ebbesen, Mette; Jensen, Thomas G.; Andersen, Svend; Pedersen, Finn Skou

2008-01-01

RNA interference is a mechanism for controlling normal gene expression which has recently begun to be employed as a potential therapeutic agent for a wide range of disorders, including cancer, infectious diseases and metabolic disorders. Clinical trials with RNA interference have begun. However, challenges such as off-target effects, toxicity and safe delivery methods have to be overcome before RNA interference can be considered as a conventional drug. So, if RNA interference is to be used therapeutically, we should perform a risk-benefit analysis. It is ethically relevant to perform a risk-benefit analysis since ethical obligations about not inflicting harm and promoting good are generally accepted. But the ethical issues in RNA interference therapeutics not only include a risk-benefit analysis, but also considerations about respecting the autonomy of the patient and considerations about justice with regard to the inclusion criteria for participation in clinical trials and health care allocation. RNA interference is considered a new and promising therapeutic approach, but the ethical issues of this method have not been greatly discussed, so this article analyses these issues using the bioethical theory of principles of the American bioethicists, Tom L. Beauchamp and James F. Childress. PMID:18612370

Oxindole: A chemical prism carrying plethora of therapeutic benefits.

PubMed

Kaur, Maninder; Singh, Manjinder; Chadha, Navriti; Silakari, Om

2016-11-10

Oxindole has emerged as a valuable scaffold in medicinal chemistry possessing diverse range of pharmacological activities. Its value has further been increased by its natural occurrence as alkaloids in variety of plants. It was first extracted from the cat claw's plant Uncaria tomentosa found in the Amazon rainforest and other tropical areas of South and Central America. Traditionally as well as present emerging therapeutic potential of oxindole nucleus has captured the interest of medicinal chemists to synthesize novel oxindole derivatives. In the present review the authors have integrated its chemistry and synthetic strategies developed after 1945. Also the information of naturally occurring oxindole alkaloids has been incorporated. The detailed pharmacological activities including anti-cancer, anti-HIV, antidiabetic, antibacterial, antioxidant, kinase inhibitory, AChE inhibitory, anti-leishmanial, β3 adrenergic receptor agonistic, phosphatase inhibitory, analgesic, spermicidal, vasopressin antagonists, progesterone antagonists, neuroprotection, and NMDA blocker activities of oxindole derivatives alongwith their SAR has also been discussed in detail. Additionally, information regarding the oxindole derivatives in clinical trials has been incorporated. Thus, this review will provide insights for the synthetic as well as medicinal chemist for the designing and synthesis of novel oxindole derivatives with novel improved range of pharmacological implications. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Nuclear delivery of a therapeutic peptide by long circulating pH-sensitive liposomes: benefits over classical vesicles.

PubMed

Ducat, E; Deprez, J; Gillet, A; Noël, A; Evrard, B; Peulen, O; Piel, G

2011-11-28

The purpose of this study is to propose a suitable vector combining increased circulation lifetime and intracellular delivery capacities for a therapeutic peptide. Long circulating classical liposomes [SPC:CHOL:PEG-750-DSPE (47:47:6 molar% ratio)] or pH-sensitive stealth liposomes [DOPE:CHEMS:CHOL:PEG(750)-DSPE (43:21:30:6 molar% ratio)] were used to deliver a therapeutic peptide to its nuclear site of action. The benefit of using stealth pH-sensitive liposomes was investigated and formulations were compared to classical liposomes in terms of size, shape, charge, encapsulation efficiency, stability and, most importantly, in terms of cellular uptake. Confocal microscopy and flow cytometry were used to evaluate the intracellular fate of liposomes themselves and of their hydrophilic encapsulated material. Cellular uptake of peptide-loaded liposomes was also investigated in three cell lines: Hs578t human epithelial cells from breast carcinoma, MDA-MB-231 human breast carcinoma cells and WI-26 human diploid lung fibroblast cells. The difference between formulations in terms of peptide delivery from the endosome to the cytoplasm and even to the nucleus was investigated as a function of time. Characterization studies showed that both formulations possess acceptable size, shape and encapsulation efficiency but cellular uptake studies showed the important benefit of the pH-sensitive formulation over the classical one, in spite of liposome PEGylation. Indeed, stealth pH-sensitive liposomes were able to deliver hydrophilic materials strongly to the cytoplasm. Most importantly, when encapsulated in pH-sensitive stealth liposomes, the peptide was able to reach the nucleus of tumorigenic and non tumorigenic breast cancer cells. Copyright © 2011 Elsevier B.V. All rights reserved.

Dispositional optimism and therapeutic expectations in early-phase oncology trials.

PubMed

Jansen, Lynn A; Mahadevan, Daruka; Appelbaum, Paul S; Klein, William M P; Weinstein, Neil D; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P

2016-04-15

Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early-phase oncology trials. However, optimism is not a unitary construct; it also can be defined as a general disposition, or what is called dispositional optimism. The authors assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. The authors also assessed how dispositional optimism related to unrealistic optimism. Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Dispositional optimism was found to be significantly associated with higher expectations for personal therapeutic benefit (Spearman rank correlation coefficient [r], 0.333; P<.0001), but was not associated with the therapeutic misconception (Spearman r, -0.075; P = .329). Dispositional optimism was found to be weakly associated with unrealistic optimism (Spearman r, 0.215; P = .005). On multivariate analysis, both dispositional optimism (P = .02) and unrealistic optimism (P<.0001) were found to be independently associated with high expectations for personal therapeutic benefit. Unrealistic optimism (P = .0001), but not dispositional optimism, was found to be independently associated with the therapeutic misconception. High expectations for therapeutic benefit among patient-subjects in early-phase oncology trials should not be assumed to result from misunderstanding of specific information regarding the trials. The data from the current study indicate that these expectations are associated with either a dispositionally positive outlook on life or biased expectations concerning specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have

Therapeutic efficacy of a therapeutic cooking group from the patients' perspective.

PubMed

Hill, Kimberly H; O'Brien, Kimberly A; Yurt, Roger W

2007-01-01

The purpose of this study was to evaluate the therapeutic efficacy of the cooking group from the burn survivors' perspective. By incorporating concepts of kitchen skills, energy conservation, and desensitization techniques, the cooking group can assist patients with the functional use of their hands, standing tolerance, return to former vocational activities, and socialization with other patients. A questionnaire was developed based on commonly expressed benefits of cooking group. Areas of interest included decreasing anxiety in the kitchen, distraction from their burns, socializing with other burn survivors, and the physical benefits of participating in the group. The results of this study indicate that participants regard the therapeutic cooking group as a valuable treatment modality that effectively combines functional activities with socialization to decrease burn related anxiety and increase motion in a supportive environment for patients with burns.

Hypotheses about the psychological benefits of horses.

PubMed

Kendall, Elizabeth; Maujean, Annick; Pepping, Christopher A; Wright, John J

2014-01-01

In the last few decades, therapeutic horse-riding has become recognized as a progressive form of therapy, particularly for people with disabilities. Although there is a substantial amount of literature that supports the physical benefit of therapeutic riding, only anecdotal evidence exists in relation to its psychological benefits. The purpose of this article is to develop hypotheses about the mechanisms by which therapeutic riding might have a beneficial psychological effect. These hypotheses can then be tested, leading to a more detailed knowledge base. PsychINFO, MEDLINE, PROQUEST, Scopus, Web of Science, and CINAHL. Data sources were searched for studies that (a) were related to the psychological effects of therapeutic horse-riding, (b) focused exclusively on therapeutic horse-riding, (c) described, explicitly or implicitly, the mechanism by which therapeutic riding had a beneficial psychological effect. Studies were limited to those published between 2008 and 2012. Data were extracted by two authors independently. Thirty articles met the inclusion criteria. Three potential hypotheses emerged from the literature, namely, (1) the psychological benefits of therapeutic riding are actually unrelated to the horse, (2) the horse provides a particularly positive context within which psychological gains are facilitated, and (3) the horse itself has specific therapeutic qualities that bring about unique changes not otherwise likely to occur. The challenge for researchers in this area is to design studies that adequately test these competing hypotheses. Copyright © 2014 Elsevier Inc. All rights reserved.

[Requirements for drug approval and additional benefits assessment: Regulatory aspects and experiences].

PubMed

Broich, K; Löbker, W; Schulte, A; Beinlich, P; Müller, T

2016-04-01

The early assessment of benefits of newly approved drugs with novel active substances or new applications, which came into force on 1 January 2011 still represents a challenge to all parties involved. This article highlights the definitions, regulatory requirements and interaction between drug marketing approval and early assessment of benefits in Germany. The constellation of an extensively harmonized European and even international drug authorization process with a predominantly national regulation of drug reimbursement situation inevitably causes friction, which could be markedly reduced through early joint advisory discussions during the planning phase for pivotal clinical trials. During the year 2015 the Federal Institute for Drugs and Medical Devices (BfArM) carried out 300 scientific advice procedures of which 34 were concerned with applications in the field of indications for the central nervous system (CNS). In comparison 98 advisory meetings were held by the Federal Joint Committee (G-BA) of which the BfArM provided advice in 12 instances and in 2 cases on CNS indications. Study design, endpoints and appropriate comparative therapies are the key issues in exchanges and discussions between the BfArM, the G‑BA and applicants. Under these aspects the BfArM and G‑BA promote an early and consistent involvement in early advice procedures regarding the prerequisites for drug approval and assessment of additional benefits.

Issues in formulary management: therapeutic interchange. The value, cost, and quality of therapeutic interchange.

PubMed

Mahoney, C D

1992-10-01

Therapeutic interchange is a process of substituting a prescribed medication with one that offers therapeutic and cost benefits. The practice not only provides short-term savings but also is associated with decreases in lengths of stay in hospitals and total hospital drug expenses. There may be medicolegal implications when FDA-approved indications differ for interchanged drugs. The potential for liability is decreased when a standard of care is met, but since standards can change, guidelines should be reviewed regularly. High-tech, high-cost drugs are sometimes appropriate for therapeutic interchange. Pharmacy and therapeutics committees should assure best value by considering indirect expenses, quality, and therapeutic outcome, as well as product cost. Therapeutic interchange programs enable pharmacy managers to neutralize or at least slow the rate of drug cost increases, ensuring appropriate utilization of resources and more favorable patient outcomes.

[Weighing use and safety of therapeutic agents and feed additives (author's transl)].

PubMed

van der Wal, P

1982-02-01

(1) The pros and cons of using feed additives and therapeutic agents may be successfully weighed in the light of carefully considered consumer requirements. (2) The socio-economic interests of the producer and the welfare of the animal will also determine the response of the production apparatus to consumer requirements. (3) Consumption of the current amounts of products of animal origin and maintenance of price and quality will only be feasible in the event of rational large-scale production in which constituents used in nutrition, prophylaxis and therapeutics are highly important factors. (4) Using these ingredients should be preceded by accurate evaluation of their use and safety. Testing facilities, conduct of studies and reporting should be such as to make the results nationally and internationally acceptable to all those concerned. (5) In deciding whether feed constituents are acceptable in view of the established use and safety, compliance will have to be sought with those standards which are accepted in other fields of society. Measures which result in raising the price of food without actually helping to reduce the risks to the safety of man, animals and environment, are likely to be rejected by any well-informed consumer who is aware of the facts. (6) For accurate weighing of use and safety at a national level, possibilities are hardly adequate in Europe. Decisions reached within the framework of the European Community, also tuned to U.S.A.- conditions are rightly encouraged. A centrally managed professionally staffed and equipped test system in the European Community would appear to be indispensable.

Therapeutic cancer vaccines

PubMed Central

Melief, Cornelis J.M.; van Hall, Thorbald; Arens, Ramon; Ossendorp, Ferry; van der Burg, Sjoerd H.

2015-01-01

The clinical benefit of therapeutic cancer vaccines has been established. Whereas regression of lesions was shown for premalignant lesions caused by HPV, clinical benefit in cancer patients was mostly noted as prolonged survival. Suboptimal vaccine design and an immunosuppressive cancer microenvironment are the root causes of the lack of cancer eradication. Effective cancer vaccines deliver concentrated antigen to both HLA class I and II molecules of DCs, promoting both CD4 and CD8 T cell responses. Optimal vaccine platforms include DNA and RNA vaccines and synthetic long peptides. Antigens of choice include mutant sequences, selected cancer testis antigens, and viral antigens. Drugs or physical treatments can mitigate the immunosuppressive cancer microenvironment and include chemotherapeutics, radiation, indoleamine 2,3-dioxygenase (IDO) inhibitors, inhibitors of T cell checkpoints, agonists of selected TNF receptor family members, and inhibitors of undesirable cytokines. The specificity of therapeutic vaccination combined with such immunomodulation offers an attractive avenue for the development of future cancer therapies. PMID:26214521

An Investigation of the Additive Benefits of Parent Dialogic Reading Techniques in Older Preschool Children

ERIC Educational Resources Information Center

Switalski, Sarah O'Neill

2012-01-01

This study examined the additive benefit of parent dialogic reading techniques in older, high-risk preschool children using multiple baseline design across participants, a single subject research design, as was as well as pre-test and post-test measures. Five preschoolers age-eligible to begin kindergarten the following school year participated.…

Cardiovascular pleiotropic actions of DPP-4 inhibitors: a step at the cutting edge in understanding their additional therapeutic potentials.

PubMed

Balakumar, Pitchai; Dhanaraj, Sokkalingam A

2013-09-01

Dipeptidyl peptidase 4 (DPP-4) is a serine protease enzyme expressed widely in many tissues, including the cardiovascular system. The incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the small intestine into the vasculature during a meal, and these incretins have a potential to release insulin from pancreatic beta cells of islets of Langerhans, affording a glucose-lowering action. However, both incretins are hurriedly degraded by the DPP-4. Inhibitors of DPP-4, therefore, enhance the bioavailability of GLP-1 and GIP, and thus have been approved for better glycemic management in patients afflicted with type 2 diabetes mellitus (T2DM). Five different DPP-4 inhibitors, often called as 'gliptins', namely sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin have been approved hitherto for clinical use. These drugs are used along with diet and exercise to lower blood sugar in diabetic subjects. T2DM is intricately related with an increased risk of cardiovascular disease. Growing body of evidence suggests that gliptins, in addition to their persuasive anti-diabetic action, have a beneficial pleiotropic action on the heart and vessels. In view of the fact of cardiovascular disease susceptibility of patients afflicted with T2DM, gliptins might offer additional therapeutic benefits in treating diabetic cardiovascular complications. Exploring further the cardiovascular pleiotropic potentials of gliptins might open a panorama in impeccably employing these agents for the dual management of T2DM and T2DM-associated perilous cardiovascular complications. This review will shed lights on the newly identified beneficial pleiotropic actions of gliptins on the cardiovascular system. Copyright © 2013 Elsevier Inc. All rights reserved.

Improving therapeutic outcomes in autism spectrum disorders: Enhancing social communication and sensory processing through the use of interactive robots.

PubMed

Sartorato, Felippe; Przybylowski, Leon; Sarko, Diana K

2017-07-01

For children with autism spectrum disorders (ASDs), social robots are increasingly utilized as therapeutic tools in order to enhance social skills and communication. Robots have been shown to generate a number of social and behavioral benefits in children with ASD including heightened engagement, increased attention, and decreased social anxiety. Although social robots appear to be effective social reinforcement tools in assistive therapies, the perceptual mechanism underlying these benefits remains unknown. To date, social robot studies have primarily relied on expertise in fields such as engineering and clinical psychology, with measures of social robot efficacy principally limited to qualitative observational assessments of children's interactions with robots. In this review, we examine a range of socially interactive robots that currently have the most widespread use as well as the utility of these robots and their therapeutic effects. In addition, given that social interactions rely on audiovisual communication, we discuss how enhanced sensory processing and integration of robotic social cues may underlie the perceptual and behavioral benefits that social robots confer. Although overall multisensory processing (including audiovisual integration) is impaired in individuals with ASD, social robot interactions may provide therapeutic benefits by allowing audiovisual social cues to be experienced through a simplified version of a human interaction. By applying systems neuroscience tools to identify, analyze, and extend the multisensory perceptual substrates that may underlie the therapeutic benefits of social robots, future studies have the potential to strengthen the clinical utility of social robots for individuals with ASD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preventing diabetic foot disease: lessons from the Medicare therapeutic shoe demonstration.

PubMed Central

Wooldridge, J; Bergeron, J; Thornton, C

1996-01-01

OBJECTIVES. Every year about 38,000 elderly people with diabetes have a lower extremity amputation. Therapeutic shoes are prescribed by clinicians specializing in foot care to prevent foot ulcerations and amputations among at-risk patients with diabetes. Medicare ran a 3-year demonstration of a therapeutic-shoe benefit for beneficiaries with diabetes. Medicare added the benefit nationwide in May 1993. METHODS. This paper describes the benefit and its implementation in the demonstration based on demonstration records, a patient survey, and discussions with clinicians and shoe suppliers before and during the demonstration. RESULTS. During the demonstration, far fewer beneficiaries applied for the therapeutic shoes than were eligible for them. The paper discusses reasons for the low beneficiary application rate and the associated low participation rate among physicians treating patients with diabetes. CONCLUSIONS. The benefit is unlikely to be used any more in the national program than in the demonstration unless physicians are educated in the role therapeutic shoes can play in diabetic foot disease, they prescribe the shoes for their patients, and they increase their patients' awareness of the shoes' value. PMID:8669516

An antidote approach to reduce risk and broaden utility of antibody-based therapeutics.

PubMed

Portnoff, Alyse D; Gao, Cuihua; Borrok, M Jack; Gao, Xizhe; Gao, Changshou; Rainey, G Jonah

2017-05-19

Antibody therapeutics offer effective treatment options for a broad range of diseases. One of the greatest benefits of antibody therapeutics is their extraordinarily long serum half-life, allowing infrequent dosing with long-lasting effects. A characteristic of antibodies that drives long half-life is the ability to interact with the recycling receptor, FcRn, in a pH-dependent manner. The benefit of long half-life, however, carries with it liabilities. Although the positive effects of antibody therapeutics are long-lasting, any acute adverse events or chronic negative impacts, such as immunosuppression in the face of an infection, are also long-lasting. Therefore, we sought to develop antibodies with a chemical handle that alone would enjoy the long half-life of normal antibodies but, upon addition of a small-molecule antidote, would interact with the chemical handle and inhibit the antibody recycling mechanism, thus leading to rapid degradation and shortened half-life in vivo Here we present a proof of concept study where we identify sites to incorporate a non-natural amino acid that can be chemically modified to modulate FcRn interaction in vitro and antibody half-life in vivo This is an important first step in developing safer therapeutics, and the next step will be development of technology that can perform the modifying chemistry in vivo . © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The benefit of therapeutic medial branch blocks after cervical operations.

PubMed

Klessinger, Stephan

2010-01-01

Persistent neck pain is a common problem after surgery of the cervical spine. No therapy recommendation exists for these patients. The objective of this study was to determine if a therapeutic medial branch block is a rational treatment for patients with postoperative neck pain after cervical spine operations. Retrospective practice audit. Review of charts of all patients who underwent cervical spine operations for degenerative reasons during a time period of 3 years. Patients with persistent postsurgical pain were treated with therapeutic medial branch blocks (local anesthetic and steroid). A positive treatment response was defined if at least 80% reduction of pain could be achieved or if the patient was sufficiently satisfied with the relief. All patients with a minimum follow up time of 6 months were included. Of the 312 operations performed, 128 were artificial disc operations, 125 were stand alone cages, and 59 were fusions with cage and plate. Persistent neck pain occurred in 33.3% of the patients. There was no difference between the patients with neck pain and the whole group of patients. More than half of the patients with neck pain--52.9%--were treated successfully with therapeutic medial branch blocks. Since no further treatment was necessary, the initial treatment was considered successful. Nearly a third--32.2%--of the patients were initially treated successfully, but their pain recurred and further diagnostics and treatments were necessary. In this group of patients, significantly more with double level operations were found (P = 0.003). Patients not responding to the medial branch block were 14.9%. This audit is retrospective and observational, and therefore does not represent a high level of evidence. However, to our knowledge, since this information has not been previously reported and no recommendation for the treatment of post-operative zygapophysial joint pain exists, it appears to be the best available research upon which to recommend treatment

[Nuclear transfer and therapeutic cloning].

PubMed

Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

2005-03-01

Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

Integration of PKPD relationships into benefit-risk analysis.

PubMed

Bellanti, Francesco; van Wijk, Rob C; Danhof, Meindert; Della Pasqua, Oscar

2015-11-01

Despite the continuous endeavour to achieve high standards in medical care through effectiveness measures, a quantitative framework for the assessment of the benefit-risk balance of new medicines is lacking prior to regulatory approval. The aim of this short review is to summarise the approaches currently available for benefit-risk assessment. In addition, we propose the use of pharmacokinetic-pharmacodynamic (PKPD) modelling as the pharmacological basis for evidence synthesis and evaluation of novel therapeutic agents. A comprehensive literature search has been performed using MESH terms in PubMed, in which articles describing benefit-risk assessment and modelling and simulation were identified. In parallel, a critical review of multi-criteria decision analysis (MCDA) is presented as a tool for characterising a drug's safety and efficacy profile. A definition of benefits and risks has been proposed by the European Medicines Agency (EMA), in which qualitative and quantitative elements are included. However, in spite of the value of MCDA as a quantitative method, decisions about benefit-risk balance continue to rely on subjective expert opinion. By contrast, a model-informed approach offers the opportunity for a more comprehensive evaluation of benefit-risk balance before extensive evidence is generated in clinical practice. Benefit-risk balance should be an integral part of the risk management plan and as such considered before marketing authorisation. Modelling and simulation can be incorporated into MCDA to support the evidence synthesis as well evidence generation taking into account the underlying correlations between favourable and unfavourable effects. In addition, it represents a valuable tool for the optimization of protocol design in effectiveness trials. © 2015 The British Pharmacological Society.

Therapeutic benefits in grid irradiation on Tomotherapy for bulky, radiation-resistant tumors.

PubMed

Narayanasamy, Ganesh; Zhang, Xin; Meigooni, Ali; Paudel, Nava; Morrill, Steven; Maraboyina, Sanjay; Peacock, Loverd; Penagaricano, Jose

2017-08-01

Spatially fractionated radiation therapy (SFRT or grid therapy) has proven to be effective in management of bulky tumors. The aim of this project is to study the therapeutic ratio (TR) of helical Tomotherapy (HT)-based grid therapy using linear-quadratic cell survival model. HT-based grid (or HT-GRID) plan was generated using a patient-specific virtual grid pattern of high-dose cylindrical regions using MLCs. TR was defined as the ratio of normal tissue surviving fraction (SF) under HT-GRID irradiation to an open debulking field of an equivalent dose that result in the same tumor cell SF. TR was estimated from DVH data on ten HT-GRID patient plans with deep seated, bulky tumor. Dependence of the TR values on radiosensitivity of the tumor cells and prescription dose was analyzed. The mean ± standard deviation (SD) of TR was 4.0 ± 0.7 (range: 3.1-5.5) for the 10 patients with single fraction maximum dose of 20 Gy to GTV assuming a tumor cell SF at 2 Gy (SF2 t ) value of 0·5. In addition, the mean ± SD of TR values for SF2 t values of 0.3 and 0.7 were found to be 1 ± 0.1 and 18.0 ± 5.1, respectively. Reducing the prescription dose to 15 and 10 Gy lowered the respective TR values to 2.0 ± 0.2 and 1.2 ± 0.04 for a SF2 t value of 0.5. HT-GRID therapy demonstrates a significant therapeutic advantage over uniform dose from an open field irradiation for the same tumor cell kill. TR increases with the radioresistance of the tumor cells and with prescription dose.

[A therapeutic education tool in paediatric dentistry].

PubMed

Marquillier, Thomas; Trentesaux, Thomas; Catteau, Céline; Delfosse, Caroline

Therapeutic education for children is developing in the treatment of dental caries. The Elmy pathway, a pedagogical game aiming to improve children's oral health skills, has been designed. The qualitative assessment of this tool seems to confirm its benefit for use in therapeutic education sessions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

[Health security--GMOs in therapeutics].

PubMed

Trouvin, J-H

2003-03-01

The recent progress in human therapeutics has been made possible thanks to molecular biology and its use in producing proteins having the same sequence and structure as that of human proteins. The use of GMOs allows production of proteins with high added value in therapeutics, which are of satisfactory quality. GMOs may also be directly administered to patients as gene therapy vectors. However, the use of GMOs in therapeutics must take into consideration some risks, particularly those of microbiological contamination, of neo-antigenicity as well as environmental risks with regard to the way of use of the GMO. Nevertheless, those risks are taken in due consideration in the development of these new medicinal products; solutions have been found to allow their use in therapeutics with a very positive benefit/risk ratio. Medicinal products from biotechnology have enabled considerable therapeutic progress without compromising health security.

Benefit assessment in Germany: implications for price discounts.

PubMed

Theidel, Ulrike; von der Schulenburg, J-Matthias Graf

2016-12-01

The AMNOG regulation, introduced in 2011 in Germany, changed the game for new drugs. Now, the industry is required to submit a dossier to the GBA (the central decision body in the German sickness fund system) to show additional benefit. After granting the magnitude of the additional benefit by the GBA, the manufacturer is entitled to negotiate the reimbursement price with the GKV-SV (National Association of Statutory Health Insurance Funds). The reimbursement price is defined as a discount on the drug price at launch. As the price or discount negotiations between the manufacturers and the GKV-SV takes place behind closed doors, the factors influencing the results of the negotiation are not known. The aim of this evaluation is to identify factors influencing the results of the AMNOG price negotiation process. The analysis was based on a dataset containing detailed information on all assessments until the end of 2015. A descriptive analysis was followed by an econometric analysis of various potential factors (benefit rating, size of target population, deviating from appropriate comparative therapy and incorporation of HRQoL-data). Until December 2015, manufacturers and the GKV-SV finalized 96 negotiations in 193 therapeutic areas, based on assessment conducted by the GBA. The GBA has granted an additional benefit to 100/193 drug innovations. Negotiated discount was significantly higher for those drugs without additional benefit (p = 0.030) and non-orphan drugs (p = 0.015). Smaller population size, no deviation from recommended appropriate comparative therapy and the incorporation of HRQoL-data were associated with a lower discount on the price at launch. However, neither a uni- nor the multivariate linear regression showed enough power to predict the final discount. Although the AMNOG regulation implemented binding and strict rules for the benefit assessment itself, the outcome of the discount negotiations are still unpredictable. Obviously, negotiation

A laboratory study of the perceived benefit of additional noise attenuation by houses

NASA Technical Reports Server (NTRS)

Flindell, I. H.

1983-01-01

Two Experiments were conducted to investigate the perceived benefit of additional house attenuation against aircraft flyover noise. First, subjects made annoyance judgments in a simulated living room while an operative window with real and dummy storm windows was manipulated in full view of those subjects. Second, subjects made annoyance judgments in an anechoic audiometric test chamber of frequency shaped noise signals having spectra closely matched to those of the aircraft flyover noises reproduced in the first experiment. These stimuli represented the aircraft flyover noises in levels and spectra but without the situational and visual cues present in the simulated living room. Perceptual constancy theory implies that annoyance tends to remain constant despite reductions in noise level caused by additional attenuation of which the subjects are fully aware. This theory was supported when account was taken for a reported annoyance overestimation for certain spectra and for a simulated condition cue overreaction.

Pharmacogenomics in the assessment of therapeutic risks versus benefits: inside the United States Food and Drug Administration.

PubMed

Zineh, Issam; Pacanowski, Michael A

2011-08-01

Pharmacogenomics is the study of how genetic variations influence responses to drugs, diagnostics, or biologic agents. The field of pharmacogenomics has significant potential to enhance drug development and aid in making regulatory decisions. The United States Food and Drug Administration (FDA) has supported pharmacogenomics for nearly a decade by providing regulatory advice and reviewing applications, with the intent of discovering and applying genetic determinants of treatment effects. The FDA will continue to develop policies and processes centered on genomics and individualized therapeutics to guide rational drug development. It will also continue to inform the public of clinically relevant pharmacogenomic issues through various mechanisms of communication, such as drug labeling. In this review, we provide a perspective on several pharmacogenomic activities at the FDA. In addition, we attempt to clarify what we believe are several misperceptions regarding the FDA's pharmacogenomic initiatives. We hope this perspective provides a window into some ways in which the FDA is enabling individualized therapeutics through its mission-critical activities.

Therapeutic cloning research and ethical oversight.

PubMed

Spriggs, M

2003-08-01

Cloning Trevor, a story about therapeutic cloning research, appeared in the June issue of The Atlantic Monthly. The story gives a human face to the people whom therapeutic cloning could benefit. It presents an argument for government funding and it puts the usual calls for a moratorium on embryonic stem cell research to allow for more debate, in a less favourable light. The story also highlights some problems with ethical oversight.

[Therapeutic hypothermia for severe traumatic brain injury].

PubMed

Bouzat, P; Francony, G; Oddo, M; Payen, J-F

2013-11-01

Therapeutic hypothermia (TH) is considered a standard of care in the post-resuscitation phase of cardiac arrest. In experimental models of traumatic brain injury (TBI), TH was found to have neuroprotective properties. However, TH failed to demonstrate beneficial effects on neurological outcome in patients with TBI. The absence of benefits of TH uniformly applied in TBI patients should not question the use of TH as a second-tier therapy to treat elevated intracranial pressure. The management of all the practical aspects of TH is a key factor to avoid side effects and to optimize the potential benefit of TH in the treatment of intracranial hypertension. Induction of TH can be achieved with external surface cooling or with intra-vascular devices. The therapeutic target should be set at a 35°C using brain temperature as reference, and should be maintained at least during 48 hours and ideally over the entire period of elevated intracranial pressure. The control of the rewarming phase is crucial to avoid temperature overshooting and should not exceed 1°C/day. Besides its use in the management of intracranial hypertension, therapeutic cooling is also essential to treat hyperthermia in brain-injured patients. In this review, we will discuss the benefit-risk balance and practical aspects of therapeutic temperature management in TBI patients. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Therapeutic Recombinant Monoclonal Antibodies

ERIC Educational Resources Information Center

Bakhtiar, Ray

2012-01-01

During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

Overview of Therapeutic Ultrasound Applications and Safety Considerations

PubMed Central

Miller, Douglas; Smith, Nadine; Bailey, Michael; Czarnota, Gregory; Hynynen, Kullervo; Makin, Inder

2013-01-01

Summary Applications of ultrasound in medicine for therapeutic purposes have been an accepted and beneficial use of ultrasonic biological effects for many years. Low power ultrasound of about 1 MHz frequency has been widely applied since the 1950s for physical therapy in conditions such as tendinitis or bursitis. In the 1980s, high pressure-amplitude shockwaves came into use for mechanically resolving kidney stones, and “lithotripsy” rapidly replaced surgery as the most frequent treatment choice. The use of ultrasonic energy for therapy continues to expand, and approved applications now include uterine fibroid ablation, cataract removal (phacoemulsification), surgical tissue cutting and hemostasis, transdermal drug delivery, and bone fracture healing, among others. Undesirable bioeffects can occur including burns for thermal-based therapies and significant hemorrhage for mechanical-based therapies (e. g. lithotripsy). In all these therapeutic applications for bioeffects of ultrasound, standardization, ultrasound dosimetry, benefits assurance and side-effects risk minimization must be carefully considered in order to insure an optimal benefit to risk ratio for the patient. Therapeutic ultrasound typically has well-defined benefits and risks, and therefore presents a tractable safety problem to the clinician. However, safety information can be scattered, confusing or subject to commercial conflict of interest. Of paramount importance for managing this problem is the communication of practical safety information by authoritative groups, such as the AIUM, to the medical ultrasound community. In this overview, the Bioeffects Committee outlines the wide range of therapeutic ultrasound methods, which are in clinical use or under study, and provides general guidance for assuring therapeutic ultrasound safety. PMID:22441920

Potential benefits of chewing gum for the delivery of oral therapeutics and its possible role in oral healthcare.

PubMed

Wessel, Stefan W; van der Mei, Henny C; Maitra, Amarnath; Dodds, Michael W J; Busscher, Henk J

2016-10-01

Over the years, chewing gum has developed from a candy towards an oral health-promoting nutraceutical. This review summarizes evidence for the oral health benefits of chewing gum, emphasizing identification of active ingredients in gum that facilitate prevention and removal of oral biofilm. Chewing of sugar-free gum yields oral health benefits that include clearance of food debris, reduction in oral dryness, increase of biofilm pH and remineralization of enamel. These basic effects of chewing gum are attributed to increased mastication and salivation. Active ingredients incorporated in chewing gums aim to expand these effects to inhibition of extrinsic tooth stain and calculus formation, enhanced enamel remineralization, reduction of the numbers of bacteria in saliva and amount of oral biofilm, neutralization of biofilm pH, and reduction of volatile sulfur compounds. Evidence for oral-health benefits of chewing gum additives is hard to obtain due to their relatively low concentrations and rapid wash-out. Clinical effects of gum additives are overshadowed by effects of increased mastication and salivation due to the chewing of gum and require daily chewing of gum for prolonged periods of time. Future studies on active ingredients should focus on specifically targeting pathogenic bacteria, whilst leaving the healthy microbiome unaffected.

[Assessing the added benefit of new ophthalmic drugs : Which additional insights can be extracted from the early benefit assessment?

PubMed

Appelrath, M; Glaeske, G

2017-12-01

Until now six ophthalmic agents have undergone the German early benefit assessment according to § 35a Social Security Code (SGB) V in a total of eleven indications. Only one agent (ocriplasmin) was recognized by the Federal Joint Committee as having an added benefit based on submitted study data for a subpopulation (indication of a considerable added benefit, limited for 5 years) and another agent, idebenone, received an added benefit due to its orphan drug designation (proof of a not quantifiable added benefit, limited for 2 years). All remaining agents (aflibercept, bromfenac, nepafenac and tafluprost/timolol) were not recognized as having an added benefit. The analysis showed that there was a lack of suitable evidence. Some reasons for the inappropriateness of the conducted trials for the usage in the early benefit assessment are the comparative therapy, the patient population included or the dosage regimens. For two agents (bromfenac and nepafenac) the pharmaceutical company did not even submit a value dossier. The examples from ophthalmology illustrate the methodological and procedural shortcomings of the assessment process and that results of an early benefit assessment should be interpreted with caution.

The use of contact lenses in low vision rehabilitation: optical and therapeutic applications.

PubMed

Vincent, Stephen J

2017-09-01

Ocular pathology that manifests at an early age has the potential to alter the vision-dependent emmetropisation mechanism, which co-ordinates ocular growth throughout childhood. The disruption of this feedback mechanism in children with congenital or early-onset visual impairment often results in the development of significant ametropia, including high levels of spherical refractive error, astigmatism and anisometropia. This review examines the use of contact lenses as a refractive correction, low vision aid and therapeutic intervention in the rehabilitation of patients with bilateral, irreversible visual loss due to congenital ocular disease. The advantages and disadvantages of the use of contact lenses for increased magnification (telescopes and microscopes) or field expansion (reverse telescopes) are discussed, along with the benefits and practical considerations for the correction of pathological high myopia. The historical and present use of therapeutic tinted contact lenses to reduce photosensitivity and nystagmus in achromatopsia, albinism and aniridia are also presented, including clinical considerations for the contact lens practitioner. In addition to the known optical benefits in comparison to spectacles for high levels of ametropia (an improved field of view for myopes and fewer inherent oblique aberrations), contact lenses may be of significant psycho-social benefit for patients with low vision, due to enhanced cosmesis and reduced conspicuity and potential related effects of improved self-esteem and peer acceptance. The contact lens correction of patients with congenital vision impairment can be challenging for both practitioner and patient but should be considered as a potential optical or therapeutic solution in modern low vision rehabilitation. © 2017 Optometry Australia.

Inhalation delivery of protein therapeutics.

PubMed

Kane, Colleen; O'Neil, Karyn; Conk, Michelle; Picha, Kristen

2013-04-01

Inhaled therapeutics are used routinely to treat a variety of pulmonary diseases including asthma, COPD and cystic fibrosis. In addition, biological therapies represent the fastest growing segment of approved pharmaceuticals. However, despite the increased availability of biological therapies, nearly all inhaled therapeutics are small molecule drugs with only a single inhaled protein therapeutic approved. There remains a significant unmet need for therapeutics in pulmonary diseases, and biological therapies with potential to alter disease progression represent a significant opportunity to treat these challenging diseases. This review provides a background into efforts to develop inhaled biological therapies and highlights some of the associated challenges. In addition, we speculate on the ideal properties of a biologic therapy for inhaled delivery.

Hypothermia after cardiac arrest: expanding the therapeutic scope.

PubMed

Bernard, Stephen

2009-07-01

Therapeutic hypothermia for 12 to 24 hrs following resuscitation from out-of-hospital cardiac arrest is now recommended by the American Heart Association for the treatment of neurological injury when the initial cardiac rhythm is ventricular fibrillation. However, the role of therapeutic hypothermia is uncertain when the initial cardiac rhythm is asystole or pulseless electrical activity, or when the cardiac arrest is primarily due to a noncardiac cause, such as asphyxia or drug overdose. Given that survival rate in these latter conditions is very low, it is unlikely that clinical trials will be undertaken to test the efficacy of therapeutic hypothermia in this setting because of the very large sample size that would be required to detect a significant difference in outcomes. Therefore, in patients with anoxic brain injury after nonventricular fibrillation cardiac arrest, clinicians will need to balance the possible benefit of therapeutic hypothermia with the possible side effects of this therapy. Given that the side effects of therapeutic hypothermia are generally easily managed in the critical care setting, and there is benefit for anoxic brain injury demonstrated in laboratory studies, consideration may be given to treat comatose post-cardiac arrest patients with therapeutic hypothermia in this setting. Because the induction of therapeutic hypothermia has become more feasible with the development of simple intravenous cooling techniques and specialized equipment for improved temperature control in the critical care unit, it is expected that therapeutic hypothermia will become more widely used in the management of anoxic neurological injury whatever the presenting cardiac rhythm.

Gardening as a therapeutic intervention in mental health.

PubMed

Page, Mathew

This article describes why one low-secure unit chose to initiate a horticultural therapy project and organise it as a 'workers' cooperative'. The therapeutic benefits of gardening are explored, particularly focusing on the social benefits. The article also discusses the issue of hope, which is an intrinsic requirement in gardening.

Image Guidance in Stem Cell Therapeutics: Unfolding the Blindfold.

PubMed

Bukhari, Amirali B; Dutta, Shruti; De, Abhijit

2015-01-01

Stem cell therapeutics is the future of regenerative medicine in the modern world. Many studies have been instigated with the hope of translating the outcome for the treatment of several disease conditions ranging from heart and neuronal disease to malignancies as grave as cancers. Stem cell therapeutics undoubtedly holds great promise on the front of regenerative medicine, however, the correct distribution and homing of these stem cells to the host site remained blinded until the recent advances in the discipline of molecular imaging. Herein, we discuss the various imaging guidance applied for determination of the proper delivery of various types of stem cell used as therapeutics for various maladies. Additionally, we scrutinize the use of several indirect labeling mechanisms for efficient tagging of the reporter entity for image guidance. Further, the promise of improving patient healthcare has led to the initiation of several clinical trials worldwide. However, in number of the cases, the benefits arrive with a price heavy enough to pose a serious health risk, one such being formation of teratomas. Thus numerous challenges and methodological obstacles must be overcome before their eloquent clinical impact can be realized. Therefore, we also discuss several clinical trials that have taken into consideration the various imaging guided protocols to monitor correct delivery and understand the distribution of therapeutic stem cells in real time.

Dance is more than therapy: Qualitative analysis on therapeutic dancing classes for Parkinson's.

PubMed

Rocha, Priscila A; Slade, Susan C; McClelland, Jodie; Morris, Meg E

2017-10-01

To understand the benefits and limitations of therapeutic dancing classes for people with Parkinson's disease (PD) and how best to design and implement classes. A stakeholder forum explored the opinions of 18 allied health clinicians, dance instructors, people with PD and caregivers. Data were thematically analysed and interpreted within a grounded theory framework. Four main themes were identified: (1) the need to consider the stage of disease progression when designing classes; (2) recognition that dance is more than just therapy; (3) the benefits of carefully selecting music to move by; (4) ways to design classes that are both feasible and engaging. These themes give rise to the theory that dancing classes can provide more than just therapeutic benefits. Dance affords creative expression and enables people to immerse themselves in the art-form, rather than focussing on the disease. The results highlight the benefits of enabling individuals with PD to be able to express themselves in a supportive environment that does not see them solely through the lens of Parkinson's. The feasibility of dance programs can be increased by educating dancing teachers about PD and the unique needs of people living with this condition. Well-structured dance classes can promote social-connectedness and joy, in addition to facilitating movement to music and physical activity. Consumers advised that careful planning of the classes and tailoring them to participant needs optimizes outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Therapeutic Potential of Anti-Inflammatory Exerkines in the Treatment of Atherosclerosis

PubMed Central

Yu, Megan; Tsai, Sheng-Feng; Kuo, Yu-Min

2017-01-01

Although many cardiovascular (CVD) medications, such as antithrombotics, statins, and antihypertensives, have been identified to treat atherosclerosis, at most, many of these therapeutic agents only delay its progression. A growing body of evidence suggests physical exercise could be implemented as a non-pharmacologic treatment due to its pro-metabolic, multisystemic, and anti-inflammatory benefits. Specifically, it has been discovered that certain anti-inflammatory peptides, metabolites, and RNA species (collectively termed “exerkines”) are released in response to exercise that could facilitate these benefits and could serve as potential therapeutic targets for atherosclerosis. However, much of the relationship between exercise and these exerkines remains unanswered, and there are several challenges in the discovery and validation of these exerkines. This review primarily highlights major anti-inflammatory exerkines that could serve as potential therapeutic targets for atherosclerosis. To provide some context and comparison for the therapeutic potential of exerkines, the anti-inflammatory, multisystemic benefits of exercise, the basic mechanisms of atherosclerosis, and the limited efficacies of current anti-inflammatory therapeutics for atherosclerosis are briefly summarized. Finally, key challenges and future directions for exploiting these exerkines in the treatment of atherosclerosis are discussed. PMID:28608819

Health Benefits of Fiber Fermentation.

PubMed

Dahl, Wendy J; Agro, Nicole C; Eliasson, Åsa M; Mialki, Kaley L; Olivera, Joseph D; Rusch, Carley T; Young, Carly N

2017-02-01

Although fiber is well recognized for its effect on laxation, increasing evidence supports the role of fiber in the prevention and treatment of chronic disease. The aim of this review is to provide an overview of the health benefits of fiber and its fermentation, and describe how the products of fermentation may influence disease risk and treatment. Higher fiber intakes are associated with decreased risk of cardiovascular disease, type 2 diabetes, and some forms of cancer. Fiber may also have a role in lowering blood pressure and in preventing obesity by limiting weight gain. Fiber is effective in managing blood glucose in type 2 diabetes, useful for weight loss, and may provide therapeutic adjunctive roles in kidney and liver disease. In addition, higher fiber diets are not contraindicated in inflammatory bowel disease or irritable bowel syndrome and may provide some benefit. Common to the associations with disease reduction is fermentation of fiber and its potential to modulate microbiota and its activities and inflammation, specifically the production of anti-inflammatory short chain fatty acids, primarily from saccharolytic fermentation, versus the deleterious products of proteolytic activity. Because fiber intake is inversely associated with all-cause mortality, mechanisms by which fiber may reduce chronic disease risk and provide therapeutic benefit to those with chronic disease need further elucidation and large, randomized controlled trials are needed to confirm causality.Teaching Points• Strong evidence supports the association between higher fiber diets and reduced risk of cardiovascular disease, type 2 diabetes, and some forms of cancer.• Higher fiber intakes are associated with lower body weight and body mass index, and some types of fiber may facilitate weight loss.• Fiber is recommended as an adjunctive medical nutritional therapy for type 2 diabetes, chronic kidney disease, and certain liver diseases.• Fermentation and the resulting shifts in

Silk-elastin-like protein biomaterials for the controlled delivery of therapeutics.

PubMed

Huang, Wenwen; Rollett, Alexandra; Kaplan, David L

2015-05-01

Genetically engineered biomaterials are useful for controlled delivery owing to their rational design, tunable structure-function, biocompatibility, degradability and target specificity. Silk-elastin-like proteins (SELPs), a family of genetically engineered recombinant protein polymers, possess these properties. Additionally, given the benefits of combining semi-crystalline silk-blocks and elastomeric elastin-blocks, SELPs possess multi-stimuli-responsive properties and tunability, thereby becoming promising candidates for targeted cancer therapeutics delivery and controlled gene release. An overview of SELP biomaterials for drug delivery and gene release is provided. Biosynthetic strategies used for SELP production, fundamental physicochemical properties and self-assembly mechanisms are discussed. The review focuses on sequence-structure-function relationships, stimuli-responsive features and current and potential drug delivery applications. The tunable material properties allow SELPs to be pursued as promising biomaterials for nanocarriers and injectable drug release systems. Current applications of SELPs have focused on thermally-triggered biomaterial formats for the delivery of therapeutics, based on local hyperthermia in tumors or infections. Other prominent controlled release applications of SELPs as injectable hydrogels for gene release have also been pursued. Further biomedical applications that utilize other stimuli to trigger the reversible material responses of SELPs for targeted delivery, including pH, ionic strength, redox, enzymatic stimuli and electric field, are in progress. Exploiting these additional stimuli-responsive features will provide a broader range of functional biomaterials for controlled therapeutics release and tissue regeneration.

The therapeutic potential of cannabinoids for movement disorders.

PubMed

Kluger, Benzi; Triolo, Piera; Jones, Wallace; Jankovic, Joseph

2015-03-01

There is growing interest in the therapeutic potential of marijuana (cannabis) and cannabinoid-based chemicals within the medical community and, particularly, for neurological conditions. This interest is driven both by changes in the legal status of cannabis in many areas and increasing research into the roles of endocannabinoids within the central nervous system and their potential as symptomatic and/or neuroprotective therapies. We review basic science as well as preclinical and clinical studies on the therapeutic potential of cannabinoids specifically as it relates to movement disorders. The pharmacology of cannabis is complex, with over 60 neuroactive chemicals identified to date. The endocannabinoid system modulates neurotransmission involved in motor function, particularly within the basal ganglia. Preclinical research in animal models of several movement disorders have shown variable evidence for symptomatic benefits, but more consistently suggest potential neuroprotective effects in several animal models of Parkinson's (PD) and Huntington's disease (HD). Clinical observations and clinical trials of cannabinoid-based therapies suggests a possible benefit of cannabinoids for tics and probably no benefit for tremor in multiple sclerosis or dyskinesias or motor symptoms in PD. Data are insufficient to draw conclusions regarding HD, dystonia, or ataxia and nonexistent for myoclonus or RLS. Despite the widespread publicity about the medical benefits of cannabinoids, further preclinical and clinical research is needed to better characterize the pharmacological, physiological, and therapeutic effects of this class of drugs in movement disorders. © 2015 International Parkinson and Movement Disorder Society.

The Therapeutic Potential of Cannabinoids for Movement Disorders

PubMed Central

Kluger, Benzi; Triolo, Piera; Jones, Wallace; Jankovic, Joseph

2014-01-01

Background There is growing interest in the therapeutic potential of marijuana (cannabis) and cannabinoid-based chemicals within the medical community and particularly for neurologic conditions. This interest is driven both by changes in the legal status of cannabis in many areas and increasing research into the roles of endocannabinoids within the central nervous system and their potential as symptomatic and/or neuroprotective therapies. We review basic science, preclinical and clinical studies on the therapeutic potential of cannabinoids specifically as it relates to movement disorders. Results The pharmacology of cannabis is complex with over 60 neuroactive chemicals identified to date. The endocannabinoid system modulates neurotransmission involved in motor function, particularly within the basal ganglia. Preclinical research in animal models of several movement disorders have shown variable evidence for symptomatic benefits but more consistently suggest potential neuroprotective effects in several animal models of Parkinson’s (PD) and Huntington’s disease (HD). Clinical observations and clinical trials of cannabinoid-based therapies suggests a possible benefit of cannabinoids for tics and probably no benefit for tremor in multiple sclerosis or dyskinesias or motor symptoms in PD. Data are insufficient to draw conclusions regarding HD, dystonia or ataxia and nonexistent for myoclonus or restless legs syndrome. Conclusions Despite the widespread publicity about the medical benefits of cannabinoids, further preclinical and clinical research is needed to better characterize the pharmacological, physiological and therapeutic effects of this class of drugs in movement disorders. PMID:25649017

Maintenance of cytosolic calcium is crucial to extend l-arginine therapeutic benefits during continuous dosing.

PubMed

Mohan, Srinidi; Harding, Lisa

2016-10-01

The therapeutic benefits associated with short-term l-arginine supplementation are lost during continuous dosing. AMP-activated protein kinase (AMPK) functional modulation has been correlated with l-arginine therapeutic effectiveness, and with tolerance development during continuous supplementation. However, the metabolic link that is responsible for AMPK functional modulation during continuous l-arginine exposure is currently not known. To explore this, we incubated HUVECs for 7 days with 100 μmol/L l-arginine, in the presence or absence of other agents; and monitored their effects for eNOS function, and on tolerance sparing effects (viz, cellular glucose accumulation, and oxidative stress). HUVEC co-incubation with 100 μmol/L l-arginine and ≤1200 mg/mL calcium (Ca 2+ ) for 7 days avoided tolerance development, with an at least 1-fold increase in the eNOS and AMPK functional activity; and an 1-fold increase in overall cellular glucose uptake. The overall cellular cytosolic Ca 2+ was below 200 nmol/L, with no change in cellular glucose and superoxide/peroxynitrite (O 2 •- /ONOO - ) level from control. However, tolerance sparing effects of at least 70% decrease in eNOS and AMPK functional response, with an 1-fold reduction in glucose uptake, and at least 2-fold increase in O 2 •- /ONOO - were observed in cells exposed for 7 days to 100 μmol/L l-arginine at Ca 2+ co-incubation concentration of >1200 mg/mL. The >1200 mg/mL Ca2+ co-incubation condition, also improved the overall cellular Ca 2+ to >200 nmol/L. Similar tolerance response was observed in cells co-treated with 100 μmol/L l-arginine and ≤1200 mg/mL Ca 2+ in the presence of Ca 2+ influx inhibitor (20 μmol/L 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetra acetic acid), or eNOS activity inhibitor (30 μmol/L l-N G -nitroarginine methyl ester). No tolerance response was seen in cells incubated for 7 days with 100 μmol/L l-arginine and ≤1200 mg/mL Ca 2+ ; even in the presence of the inhibitor for

A Benefit-Risk Analysis Approach to Capture Regulatory Decision-Making: Non-Small Cell Lung Cancer.

PubMed

Raju, G K; Gurumurthi, K; Domike, R; Kazandjian, D; Blumenthal, G; Pazdur, R; Woodcock, J

2016-12-01

Drug regulators around the world make decisions about drug approvability based on qualitative benefit-risk analyses. There is much interest in quantifying regulatory approaches to benefit and risk. In this work the use of a quantitative benefit-risk analysis was applied to regulatory decision-making about new drugs to treat advanced non-small cell lung cancer (NSCLC). Benefits and risks associated with 20 US Food and Drug Administration (FDA) decisions associated with a set of candidate treatments submitted between 2003 and 2015 were analyzed. For benefit analysis, the median overall survival (OS) was used where available. When not available, OS was estimated based on overall response rate (ORR) or progression-free survival (PFS). Risks were analyzed based on magnitude (or severity) of harm and likelihood of occurrence. Additionally, a sensitivity analysis was explored to demonstrate analysis of systematic uncertainty. FDA approval decision outcomes considered were found to be consistent with the benefit-risk logic. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Therapeutic horse back riding of a spinal cord injured veteran: a case study.

PubMed

Asselin, Glennys; Penning, Julius H; Ramanujam, Savithri; Neri, Rebecca; Ward, Constance

2012-01-01

To determine an incomplete spinal cord injured veteran's experience following participation in a therapeutic horseback riding program. Following the establishment of a nationwide therapeutic riding program for America's wounded service veterans in 2007, a Certified Rehabilitation Registered Nurse from the Michael E. DeBakey Veteran Affairs Medical Center worked with an incomplete spinal cord injured veteran who participated in the Horses for Heroes program. This program resulted in many benefits for the veteran, including an increase in balance, muscle strength, and self-esteem. A physical, psychological, and psychosocial benefit of therapeutic horseback riding is shown to have positive results for the spinal cord injured. Therapeutic riding is an emerging field where the horse is used as a tool for physical therapy, emotional growth, and learning. Veterans returning from the Iraq/Afghanistan war with traumatic brain injuries, blast injuries, depression, traumatic amputations, and spinal cord injuries may benefit from this nurse-assisted therapy involving the horse. © 2012 Association of Rehabilitation Nurses.

Prospective, comparative cohort studies and their contribution to the benefit assessments of therapeutic options: heart failure treatment with and without Hawthorn special extract WS 1442.

PubMed

Habs, M

2004-08-01

In addition to testing a drug for its efficacy, pharmacological quality and safety, current policies are increasingly demanding evaluations of the therapeutic benefits provided by a drug in general practice with "non-selected" patients and increasingly restrictive economic considerations. One of the trials which addresses this task is the WISO cohort study (Efficacy and socio-economic relevance of treatment of chronic heart failure stage NYHA II with Crataegus extract WS 1442). It compares two different therapeutic strategies in the treatment of heart failure stage NYHA II, i.e. a conventional medication and a therapy which also includes hawthorn special extract WS 1442 (Crataegutt novo 450) in addition to chemical-synthetic drugs. In contrast to clinical trials, the patients in cohort studies are expressly not randomised and the physician in charge independently chooses the administered treatment. This comparative, non-interventional observation provides well-founded evidence of the "real-world effectiveness" of the tested preparation. 952 patients with heart failure (NYHA II) were enrolled in the study by 217 general practitioners. 588 patients received Crataegus special extract WS 1442 (Crataegutt novo 450) either as an add-on therapy or as a monotherapy (Crataegus cohort) and 364 patients received therapy without hawthorn (comparative cohort). These two groups had the same indication (heart failure NYHA II) but were significantly different regarding gender, age and concomitant cardiovascular disease. Basically, in view of the free choice of therapy made by the physician in charge, such differences are to be expected in comparative observational studies. A sufficient degree of patient comparability was provided by means of the matched-pairs technique, which replaced the randomisation procedure normally used in clinical studies. After 2 years, 130 patient pairs generated by this technique could be included in the interim assessment. The clinical symptoms with

Early investigational tubulin inhibitors as novel cancer therapeutics.

PubMed

Nepali, Kunal; Ojha, Ritu; Lee, Hsueh-Yun; Liou, Jing-Ping

2016-08-01

Microtubules represent one of the most logical and strategic molecular targets amongst the current targets for chemotherapy, alongside DNA. In the past decade, tubulin inhibitors as cancer therapeutics have been an area of focus due to the improved understanding and biological relevance of microtubules in cellular functions. Fueled by the objective of developing novel chemotherapeutics and with the aim of establishing the benefits of tubulin inhibition, several clinical trials have been conducted with others ongoing. At present, the antitubulin development pipeline contains an armful of agents under clinical investigation. This review focuses on novel tubulin inhibitors as cancer therapeutics. The article covers the agents which have completed the phase II studies along with the agents demonstrating promising results in phase I studies. Countless clinical trials evaluating the efficacy, safety and pharmacokinetics of novel tubulin inhibitors highlights the scientific efforts being paid to establish their candidature as cancer therapeutics. Colchicine binding site inhibitors as vascular disrupting agents (VDAs) and new taxanes appear to be the most likely agents for future clinical interest. Numerous agents have demonstrated clinical benefits in terms of efficacy and survival in phase I and II studies. However conclusive benefits can only be ascertained on the basis of phase III studies.

Update in therapeutic strategies for Parkinson's disease.

PubMed

Kulisevsky, Jaime; Oliveira, Lais; Fox, Susan H

2018-05-08

To review recent advances in therapeutics for motor and nonmotor symptoms of Parkinson's disease. Neuroprotection remains a large area of investigation with preliminary safety data on alpha synuclein immunotherapy and glucagon-like peptide-1 agonists. Novel Monoamine Oxidase B and Caetchol-O-methyltransferase-inhibitors for motor fluctuations have shown benefit and are recently approved for clinical use. Long-acting amantadine has also been approved to reduce dyskinesia. Alternative delivery strategies (sublingual, inhaled) dopaminergics may prove useful for rapid reversal of Parkinson's disease motor symptoms. Advanced therapies (surgery and infusional therapies) continue to be useful in subgroups of patients for motor complications with improved safety and also benefit on some nonmotor symptoms, including neuropsychiatric issues. Specific therapeutics for cognition, swallowing, sleep, and mood disorders had moderate to limited benefits. Exercise-based therapy appears beneficial at all stages of Parkinson's disease. The motor symptoms of Parkinson's disease can be reasonably treated and managed. However, therapies to slow or prevent disease progression remain a focus of research. Despite increased studies, treating nonmotor symptoms remains a challenge and an ongoing priority.

Communication about the Risks and Benefits of Phase I Pediatric Oncology Trials

PubMed Central

Hazen, Rebecca A.; Zyzanski, Stephen; Baker, Justin; Drotar, Dennis; Kodish, Eric

2015-01-01

Introduction Phase 1 pediatric oncology trials offer only a small chance of direct benefit and may have significant risks and an impact on quality of life. To date, research has not examined discussions of risks and benefits during informed consent conferences for phase 1 pediatric oncology trials. The objective of the current study was to examine clinician and family communication about risks, benefits, and quality of life during informed consent conferences for phase 1 pediatric oncology trials. Methods Participants included clinician investigators, parents, and children recruited from 6 sites conducting phase 1 pediatric oncology trials. Eighty-five informed consent conferences were observed and audiotaped. Trained coders assessed discussions of risks, benefits, and quality of life. Types of risks discussed were coded (e.g., unanticipated risks, digestive system risks, death). Types of benefits were categorized as therapeutic (e.g. discussion of how participation may or may not directly benefit child), psychological, bridge to future trial, and altruism. Results Risks and benefits were discussed in 95% and 88% of informed consent conferences, respectively. Therapeutic benefit was the most frequently discussed benefit. The impact of trial participation on quality of life was discussed in the majority (88%) of informed consent conferences. Conclusion Therapeutic benefit, risks, and quality of life were frequently discussed. The range of information discussed during informed consent conferences suggests the need for considering a staged process of informed consent for phase 1 pediatric oncology trials. PMID:25638751

Therapeutic Uses of Music with Older Adults. Second Edition

ERIC Educational Resources Information Center

Clair, Alicia Ann; Memmott, Jenny

2008-01-01

In this comprehensively updated second edition, written by Alicia Ann Clair and Jenny Memmott the extraordinary benefits of music therapy for older adults are detailed. "Therapeutic Uses of Music with Older Adults" not only examines these benefits but also clarifies the reasons that music is beneficial. This important book shows both informal and…

Therapeutic Modalities in Diabetic Nephropathy: Future Approaches*

PubMed Central

Reeves, William Brian; Rawal, Bishal B.; Abdel-Rahman, Emaad M.; Awad, Alaa S.

2012-01-01

Diabetes mellitus is the leading cause of end stage renal disease and is responsible for more than 40% of all cases in the United States. Several therapeutic interventions for the treatment of diabetic nephropathy have been developed and implemented over the past few decades with some degree of success. However, the renal protection provided by these therapeutic modalities is incomplete. More effective approaches are therefore urgently needed. Recently, several novel therapeutic strategies have been explored in treating DN patients including Islet cell transplant, Aldose reductase inhibitors, Sulodexide (GAC), Protein Kinase C (PKC) inhibitors, Connective tissue growth factor (CTGF) inhibitors, Transforming growth factor-beta (TGF-β) inhibitors and bardoxolone. The benefits and risks of these agents are still under investigation. This review aims to summarize the utility of these novel therapeutic approaches. PMID:23293752

Revisiting the Dialogue on the Transition from Coteaching to Inservice Teaching: New Frameworks, Additional Benefits and Emergent Issues

ERIC Educational Resources Information Center

Wassell, Beth; LaVan, Sarah Kate

2009-01-01

In this rejoinder, we respond to the major points made by Gallo-Fox (this forum), Beers (this forum), Carambo and Stickney (this forum), and Murphy, Carlisle and Beggs (this forum). We focus primarily on the benefits and considerations that stem from employing additional theoretical frameworks for analyzing research in coteaching. We also address…

Therapeutic appropriation: a new concept in the ethics of clinical research.

PubMed

McDougall, Rosalind; Martin, Dominique; Gillam, Lynn; Hallowell, Nina; Brookes, Alison; Guillemin, Marilys

2016-12-01

Ethical concerns about therapeutic misconception have been raised since the early 1980s. This concept was originally described as research participants' assumptions that decisions relating to research interventions are made on the basis of their individual therapeutic needs. The term has since been used to refer to a range of 'misunderstandings' that research participants may have. In this paper, we describe a new concept-therapeutic appropriation Therapeutic appropriation occurs when patients, or clinicians, actively reframe research participation as an opportunity to enhance patients' clinical care, while simultaneously acknowledging the generalised research aims. To illustrate the concept of therapeutic appropriation, we draw on data from an interview study which we conducted to investigate the experiences of patients and general practitioners involved in clinical trials in primary care. We argue that therapeutic appropriation has two key elements: comprehension that the research project is not necessarily aiming to benefit participants and the deliberate use of incidental features of the research for personal therapeutic benefit of various kinds. We conclude that therapeutic appropriation is a useful concept that refines understanding of potential ethical problems in clinical research, and points to strategies to address them. 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/.

Therapeutic Effects of Brief Hospitalization

PubMed Central

LIEBERMAN, PAUL B.; VON REHN, SUSAN; DICKIE, ELLEN; ELLIOTT, BINETTE; EGERTER, ELISE

1992-01-01

Correlational data in this study suggest that a strong therapeutic alliance is associated with improvement during brief hospitalization. Two measures of alliance were used: patient-staff agreement on treatment goals and patient expectations of benefit from treatment. Greater patient-staff agreement at admission was associated with symptomatic improvement, independent of medication use; less use of immature defense mechanisms at discharge; and reduced risk of precipitous discharge. For a given level of symptoms, greater agreement was associated with lower doses of antipsychotics but higher doses of minor tranquilizers and antidepressants. Perception of the ward was associated with patients’ expectation of benefit. PMID:22700056

Benefits of sensory garden and horticultural activities in dementia care: a modified scoping review.

PubMed

Gonzalez, Marianne T; Kirkevold, Marit

2014-10-01

To provide a review on the benefits associated with the use of sensory gardens and horticultural activities in dementia care. Maintaining quality of life is important in dementia care. Sensory gardens and horticultural activities are increasingly used in dementia care, yet their benefits are uncertain. A modified scoping review with descriptive analysis of selected empirical studies. Systematic searches in Amed, CINAHL, MEDLINE, ISI Web of Science, Embase and Scopus were used. Search terms were the free-text concepts 'healing garden', 'horticultural therapy', 'restorative garden' and 'wander garden' which were combined with dementia and Alzheimer. Sixteen studies were included with included participants ranging from eight to 129 participants. Research designs were case studies (n = 2), survey (n = 1), intervention studies with pretest/post-test design (n = 11) and randomised controlled studies (n = 2). Of these 16 studies, eight examined the benefits of sensory gardens, seven examined horticultural therapy or therapeutic horticulture and one examined the use of plants indoors. This study offers a review of the research addressing benefits of sensory gardens, therapeutic horticulture, horticultural therapy and other purposeful use of plants in dementia care. The reported findings are mainly on issues related to behaviour, affect and well-being. The findings are in general mutually supportive, however, with some contradictory findings. In addition, sleep pattern, well-being and functional level seem to improve. These types of nonpharmacological interventions may improve well-being and affect and reduce the occurrence of disruptive behaviour. Additionally, the use of psychotropic drugs, incidents of serious falls, sleep and sleep pattern also seem to improve. To further improve the use of the existing or planned gardens, an educational programme for staff that also includes skill training is recommended. © 2013 John Wiley & Sons Ltd.

Restoration of central nervous system alpha-N-acetylglucosaminidase activity and therapeutic benefits in mucopolysaccharidosis IIIB mice by a single intracisternal recombinant adeno-associated viral type 2 vector delivery.

PubMed

Fu, Haiyan; DiRosario, Julianne; Kang, Lu; Muenzer, Joseph; McCarty, Douglas M

2010-07-01

Finding efficient central nervous system (CNS) delivery approaches has been the major challenge facing therapeutic development for treating diseases with global neurological manifestation, such as mucopolysaccharidosis (MPS) IIIB, a lysosomal storage disease, caused by autosomal recessive defect of alpha-N-acetylglucosaminidase (NaGlu). Previously, we developed an approach, intracisternal (i.c.) injection, to deliver recombinant adeno-associated viral (rAAV) vector to the CNS of mice, leading to a widespread periventricular distribution of transduction. In the present study, we delivered rAAV2 vector expressing human NaGlu into the CNS of MPS IIIB mice by an i.c. injection approach, to test its therapeutic efficacy and feasibility for treating the neurological manifestation of the disease. We demonstrated significant functional neurological benefits of a single i.c. vector infusion in adult MPS IIIB mice. The treatment slowed the disease progression by mediating widespread recombinant NaGlu expression in the CNS, resulting in the reduction of brain lysosomal storage pathology, significantly improved cognitive function and prolonged survival. However, persisting motor function deficits suggested that pathology in areas outside the CNS contributes to the MPS IIIB behavioral phenotype. The therapeutic benefit of i.c. rAAV2 delivery was dose-dependent and could be attribute solely to the CNS transduction because the procedure did not lead to detectable transduction in somatic tissues. A single IC rAAV2 gene delivery is functionally beneficial for treating the CNS disease of MPS IIIB in mice. It is immediately clinically translatable, with the potential of improving the quality of life for patients with MPS IIIB.

Therapeutic intraspinal microstimulation improves forelimb function after cervical contusion injury

NASA Astrophysics Data System (ADS)

Kasten, M. R.; Sunshine, M. D.; Secrist, E. S.; Horner, P. J.; Moritz, C. T.

2013-08-01

Objective. Intraspinal microstimulation (ISMS) is a promising method for activating the spinal cord distal to an injury. The objectives of this study were to examine the ability of chronically implanted stimulating wires within the cervical spinal cord to (1) directly produce forelimb movements, and (2) assess whether ISMS stimulation could improve subsequent volitional control of paretic extremities following injury. Approach. We developed a technique for implanting intraspinal stimulating electrodes within the cervical spinal cord segments C6-T1 of Long-Evans rats. Beginning 4 weeks after a severe cervical contusion injury at C4-C5, animals in the treatment condition received therapeutic ISMS 7 hours/day, 5 days/week for the following 12 weeks. Main results. Over 12 weeks of therapeutic ISMS, stimulus-evoked forelimb movements were relatively stable. We also explored whether therapeutic ISMS promoted recovery of forelimb reaching movements. Animals receiving daily therapeutic ISMS performed significantly better than unstimulated animals during behavioural tests conducted without stimulation. Quantitative video analysis of forelimb movements showed that stimulated animals performed better in the movements reinforced by stimulation, including extending the elbow to advance the forelimb and opening the digits. While threshold current to elicit forelimb movement gradually increased over time, no differences were observed between chronically stimulated and unstimulated electrodes suggesting that no additional tissue damage was produced by the electrical stimulation. Significance. The results indicate that therapeutic intraspinal stimulation delivered via chronic microwire implants within the cervical spinal cord confers benefits extending beyond the period of stimulation, suggesting future strategies for neural devices to promote sustained recovery after injury.

Therapeutic intraspinal microstimulation improves forelimb function after cervical contusion injury

PubMed Central

Kasten, M.R.; Sunshine, M.D.; Secrist, E.S.; Horner, P.J.; Moritz, C.T.

2013-01-01

Objective Intraspinal microstimulation (ISMS) is a promising method for activating the spinal cord distal to an injury. The objectives of this study were to examine the ability of chronically implanted stimulating wires within the cervical spinal cord to (1) directly produce forelimb movements, and (2) assess whether ISMS stimulation improved subsequent volitional control of paretic extremities following injury. Approach We developed a technique for implanting intraspinal stimulating electrodes within the cervical spinal cord segments C6-T1 of Long-Evans rats. Beginning 4 weeks after a severe cervical contusion injury at C4–C5, animals in the treatment condition received therapeutic ISMS 7 hours/day, 5 days/week for the following 12 weeks. Main Results Over 12 weeks of therapeutic ISMS, stimulus-evoked forelimb movements were relatively stable. We also explored whether therapeutic ISMS promotes recovery of forelimb reaching movements. Animals receiving daily therapeutic ISMS performed significantly better than unstimulated animals during behavioral tests conducted without stimulation. Quantitative video analysis of forelimb movements showed that stimulated animals performed better in the movements reinforced by stimulation, including extending the elbow to advance the forelimb and opening the digits. While threshold current to elicit forelimb movement gradually increased over time, no differences were observed between chronically stimulated and unstimulated electrodes suggesting that no additional tissue damage was produced by the electrical stimulation. Significance The results indicate that therapeutic intraspinal stimulation delivered via chronic microwire implants within the cervical spinal cord confers benefits extending beyond the period of stimulation, suggesting future strategies for neural devices to promote sustained recovery after injury. PMID:23715242

How Exercise Can Benefit Older Patients. A Practical Approach.

ERIC Educational Resources Information Center

Barry, Henry C.; And Others

1993-01-01

Physical activity has preventive and therapeutic benefits for the frail elderly. Physicians must educate patients about exercise benefits. Walking, flexibility, and strength training can prevent muscle weakness and impaired gait and balance. Changes in functional capacity can create greater independence in daily living. Physical activity also…

[Therapeutic mediation tools for the benefit of the child and teenager].

PubMed

Rocaboy, Claudette

2016-01-01

Therapeutic mediation is a tool adapted to teenagers with a chronic disease such as diabetes. Psychodrama, dramatherapy and photolanguage in particular, enable them to express themselves more freely through both speech and body, thanks to the enjoyment they get from the game, the reassurance provided by the group, the structured setting and the spontaneity they allow. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The benefit of using additional hydrological information from earth observations and reanalysis data on water allocation decisions in irrigation districts

NASA Astrophysics Data System (ADS)

Kaune, Alexander; López, Patricia; Werner, Micha; de Fraiture, Charlotte

2017-04-01

Hydrological information on water availability and demand is vital for sound water allocation decisions in irrigation districts, particularly in times of water scarcity. However, sub-optimal water allocation decisions are often taken with incomplete hydrological information, which may lead to agricultural production loss. In this study we evaluate the benefit of additional hydrological information from earth observations and reanalysis data in supporting decisions in irrigation districts. Current water allocation decisions were emulated through heuristic operational rules for water scarce and water abundant conditions in the selected irrigation districts. The Dynamic Water Balance Model based on the Budyko framework was forced with precipitation datasets from interpolated ground measurements, remote sensing and reanalysis data, to determine the water availability for irrigation. Irrigation demands were estimated based on estimates of potential evapotranspiration and coefficient for crops grown, adjusted with the interpolated precipitation data. Decisions made using both current and additional hydrological information were evaluated through the rate at which sub-optimal decisions were made. The decisions made using an amended set of decision rules that benefit from additional information on demand in the districts were also evaluated. Results show that sub-optimal decisions can be reduced in the planning phase through improved estimates of water availability. Where there are reliable observations of water availability through gauging stations, the benefit of the improved precipitation data is found in the improved estimates of demand, equally leading to a reduction of sub-optimal decisions.

Stromal cells in breast cancer as a potential therapeutic target

PubMed Central

Dykes, Samantha S.; Hughes, Veronica S.; Wiggins, Jennifer M.; Fasanya, Henrietta O.; Tanaka, Mai; Siemann, Dietmar

2018-01-01

Breast cancer in the United States is the second most commonly diagnosed cancer in women. About 1 in 8 women will develop invasive breast cancer over the course of her lifetime and breast cancer remains the second leading cause of cancer-related death. In pursuit of novel therapeutic strategies, researchers have examined the tumor microenvironment as a potential anti-cancer target. In addition to neoplastic cells, the tumor microenvironment is composed of several critical normal cell types, including fibroblasts, vascular and lymph endothelial cells, osteoclasts, adipocytes, and immune cells. These cells have important roles in healthy tissue stasis, which frequently are altered in tumors. Indeed, tumor-associated stromal cells often contribute to tumorigenesis, tumor progression, and metastasis. Consequently, these host cells may serve as a possible target in anti-tumor and anti-metastatic therapeutic strategies. Targeting the tumor associated host cells offers the benefit that such cells do not mutate and develop resistance in response to treatment, a major cause of failure in cancer therapeutics targeting neoplastic cells. This review discusses the role of host cells in the tumor microenvironment during tumorigenesis, progression, and metastasis, and provides an overview of recent developments in targeting these cell populations to enhance cancer therapy efficacy.

[Patients' intervention in a therapeutic education program dedicated to systemic lupus: definitions, setting and benefits].

PubMed

Hervier, B; Magar, Y; Allab, F; Richard, K; Neves, Y; Danjou, S; Amoura, Z; Ayçaguer, S

2015-10-01

Though recommended, participation of patients with specific expertise in therapeutic education programs (TEP) is rare. This work reports the experience of a national reference centre for rare systemic diseases. Involvement of "expert patients" (EP) has been planned from the development of a TEP dedicated to systemic lupus: patients' roles and required expertise have been defined and linked to the pedagogical tools. Such patients have been recruited during individual interviews and called to participate to specific pedagogical training. EP intervention have been evaluated by questionnaire to EP and health care providers. Three EP's functions have been identified: sharing experiences, giving "tips and tricks" and promoting dialogue. EP's interventions has been organised into a hierarchy (from sharing to co-animation). Among 298 patients enrolled in the TEP, 25 (8.4%) have been identified as possible EP. Eight of them (32%) benefited from a specific training of 12 hours. Among these patients, two (25%) regularly participate to the education sessions. For EP as well as for health care providers, EP's intervention seems beneficial (visual scale scores of 7.5 and 9.5, respectively). Though difficult to organise, EP's intervention in TEP dedicated to rare systemic diseases seems useful and would earn to be increase. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Charcoal addition to soils in NE England: a carbon sink with environmental co-benefits?

PubMed

Bell, M J; Worrall, F

2011-04-01

Interest in the application of biochar (charcoal produced during the pyrolysis of biomass) to agricultural land is increasing across the world, recognised as a potential way to capture and store atmospheric carbon. Its interest is heightened by its potential co-benefits for soil quality and fertility. The majority of research has however been undertaken in tropical rather than temperate regions. This study assessed the potential for lump-wood charcoal addition (as a substitute for biochar) to soil types which are typically under arable and forest land-use in North East England. The study was undertaken over a 28 week period and found: i) No significant difference in net ecosystem respiration (NER) between soils containing charcoal and those without, other than in week 1 of the trial. ii) A significantly higher dissolved organic carbon (DOC) flux from soils containing large amounts of charcoal than from those untreated, when planted with ryegrass. iii) That when increased respiration or DOC loss did occur, neither was sufficiently large to alter the carbon sink benefits of charcoal application. iv) That charcoal incorporation resulted in a significantly lower nitrate flux in soil leachate from mineral soils. v) That charcoal incorporation caused significant increases in soil pH, from 6.98 to 7.22 on bare arable soils when 87,500 kg charcoal/ha was applied. Consideration of both the carbon sink and environmental benefits observed here suggests that charcoal application to temperate soils typical of North East England should be considered as a method of carbon sequestration. Before large scale land application is encouraged, further large scale trials should be undertaken to confirm the positive results of this research. Copyright © 2011 Elsevier B.V. All rights reserved.

Impact of a pharmacist-driven warfarin management protocol on achieving therapeutic International Normalized Ratios.

PubMed

Downing, Amanda; Mortimer, Molly; Hiers, Jill

2016-03-01

Warfarin is a high alert medication and a challenge to dose and monitor. Pharmacist-driven warfarin management has been shown to decrease the time international normalized ratio (INR) is out of range, which may reduce undesired outcomes. The purpose of this study is to assess the effect of the implementation of a pharmacist-driven warfarin management protocol on the achievement of therapeutic INRs. A warfarin management protocol was developed using evidence based literature and similar protocols from other institutions. Pharmacists utilized the protocol to provide patient specific warfarin dosing upon provider referral. To evaluate the protocol's impact, a retrospective chart review pre- and post-implementation was completed for admitted patients receiving warfarin. Three hundred twenty-seven charts were reviewed for pre- and post-implementation data. INRs within therapeutic range increased from 27.8% before protocol implementation to 38.5% after implementation. There was also a reduction in subtherapeutic INRs (55.3% pre to 39% post) and supratherapeutic INRs 5 or above (3.7% pre to 2.6% post). Supratherapeutic INRs between 3 and 5 did increase from 13.2% before protocol implementation to 19.9% in the pharmacist managed group. In addition to reducing the time to achievement of therapeutic INRs by 0.5 days, implementation of the protocol resulted in an increased the number of patients with at least one therapeutic INR during admission (35% pre to 40% post). The implementation of a pharmacist-driven warfarin dosing protocol increased therapeutic INRs, and decreased the time to therapeutic range, as well as the proportion of subtherapeutic INRs and supratherapeutic INRs 5 or greater. Additional benefits of the protocol include documentation of Joint Commission National Patient Safety Goal compliance, promotion of interdisciplinary collaboration and increased continuity of care. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights

Therapeutic Duplicates in a Cohort of Hospitalized Elderly Patients: Results from the REPOSI Study.

PubMed

Pasina, Luca; Astuto, Sarah; Cortesi, Laura; Tettamanti, Mauro; Franchi, Carlotta; Marengoni, Alessandra; Mannucci, Pier Mannuccio; Nobili, Alessandro

2016-09-01

Explicit criteria for potentially inappropriate prescriptions in the elderly are recommended to avoid prescriptions of duplicate drug classes and to optimize monotherapy within a single drug class before a new agent is considered. Duplicate drug class prescription (or therapeutic duplicates) puts the patient at increased risk of adverse drug reactions with no additional therapeutic benefits. To our knowledge, the prevalence of elderly inpatients receiving therapeutic duplicates has never been studied. Our objective was to assess the prevalence of therapeutic duplicates at admission, discharge, and 3-month follow-up of hospitalized elderly patients. This cross-sectional prospective study was conducted in 97 Italian internal medicine and geriatric wards. Therapeutic duplicates were defined as at least two drugs of the same therapeutic class prescribed simultaneously to a patient. A patient's drug therapy at admission relates to prescriptions from general practitioners, whereas prescriptions at discharge are those from hospital internists or geriatricians. The study sample comprised 5821 admitted and 4983 discharged patients. In all, 143 therapeutic duplicates were found at admission and 170 at discharge. The prevalence of patients exposed to at least one therapeutic duplicate rose significantly from hospital admission (2.5 %) to discharge (3.4 %; p = 0.0032). Psychotropic drugs and drugs for peptic ulcer or gastroesophageal reflux disease were the most frequently involved. A total of 86.8 % of patients discharged with at least one therapeutic duplicate were still receiving them at 3-month follow-up. Hospitalization and drugs prescribed by internists and geriatricians are both factors associated with a small but definite increase in overall therapeutic duplicates in elderly patients admitted to internal medicine and geriatric wards. More attention should be paid to the indications for each drug prescribed, because therapeutic duplicates are not supported by evidence

College and Community Partnerships: Extending the Benefits of Therapeutic Recreation to Veterans

ERIC Educational Resources Information Center

Fuchs, Steven J.; Cannella, Lee grace; Pisano, Susan

2014-01-01

In fall 2010, St. Joseph's College initiated a partnership between the college, Northport VA Medical Center, and Long Island State Veterans Home that provides a therapeutic platform for the integration of the three communities through sustainable and mutually beneficial curricular and co-curricular service and experiential learning programs. In…

The 2016 HIGh Heels: Health effects And psychosexual BenefITS (HIGH HABITS) study: systematic review of reviews and additional primary studies.

PubMed

Barnish, Max; Morgan, Heather May; Barnish, Jean

2017-08-01

High-heeled shoes (high heels) are frequently worn by many women and form an important part of female gender identity. Issues of explicit and implicit compulsion to wear high heels have been noted. Previous studies and reviews have provided evidence that high heels are detrimental to health. However, the evidence base remains fragmented and no review has covered both the epidemiological and biomechanical literature. In addition, no review has considered the psychosexual benefits that offer essential context in understanding the public health challenge of high heels. We searched seven major bibliographic databases up to November 2016, in addition to supplementary searches. We initially identified all review articles of any design that assessed either the psychosexual benefits or negative musculoskeletal health effects of high heels, the latter looking at both the epidemiological and biomechanical perspectives. We additionally considered additional primary studies on areas that had not been reviewed before or in which a marked lack of evidence had been noted. Data were extracted onto standardised forms. Proportionate second review was conducted. A total of 506 unique records were identified, 27 full-text publications were screened and 20 publications (7 reviews and 13 additional studies) were included in our evidence synthesis. The most up-to-date epidemiological review provides clear evidence of an association between high heel wear and hallux valgus, musculoskeletal pain and first-party injury. The body of biomechanical reviews provides clear evidence of changes indicative of increased risk of these outcomes, as well as osteoarthritis, which is not yet evidenced by epidemiological studies. There were no reviews on psychosexual benefits, but all five identified original studies provided evidence of increased attractiveness and/or an impact on men's behaviour associated with high heel wear. With regard to second-party injury, evidence is limited to one descriptive

Curcumin Nanomedicine: A Road to Cancer Therapeutics

PubMed Central

Yallapu, Murali M.; Jaggi, Meena; Chauhan, Subhash C.

2013-01-01

Cancer is the second leading cause of death in the United States. Conventional therapies cause widespread systemic toxicity and lead to serious side effects which prohibit their long term use. Additionally, in many circumstances tumor resistance and recurrence is commonly observed. Therefore, there is an urgent need to identify suitable anticancer therapies that are highly precise with minimal side effects. Curcumin is a natural polyphenol molecule derived from the Curcuma longa plant which exhibits anticancer, chemo-preventive, chemo- and radio-sensitization properties. Curcumin’s widespread availability, safety, low cost and multiple cancer fighting functions justify its development as a drug for cancer treatment. However, various basic and clinical studies elucidate curcumin’s limited efficacy due to its low solubility, high rate of metabolism, poor bioavailability and pharmacokinetics. A growing list of nanomedicine(s) using first line therapeutic drugs have been approved or are under consideration by the Food and Drug Administration (FDA) to improve human health. These nanotechnology strategies may help to overcome challenges and ease the translation of curcumin from bench to clinical application. Prominent research is reviewed which shows that advanced drug delivery of curcumin (curcumin nanoformulations or curcumin nanomedicine) is able to leverage therapeutic benefits by improving bioavailability and pharmacokinetics which in turn improves binding, internalization and targeting of tumor(s). Outcomes using these novel drug delivery systems have been discussed in detail. This review also describes the tumor-specific drug delivery system(s) that can be highly effective in destroying tumors. Such new approaches are expected to lead to clinical trials and to improve cancer therapeutics. PMID:23116309

Language Patterns and Therapeutic Change.

ERIC Educational Resources Information Center

Phoenix, Valdemar G.; Lindeman, Mary L.

Noting that the mental health practitioner needs highly developed linguistic and communicative skills in order to precipitate therapeutic changes, this paper discusses the nature of the contexts of therapeutic interaction. It examines verb tense as a linguistic context marker and shows how various schools of therapy can use it. In addition, it…

Evaluation of Risk Versus Benefit Information in Direct-To-Consumer (DTC) Prescription Drug Television Advertisements.

PubMed

Fahim, Germin; Toscani, Michael; Barone, Joseph A; Wang, Chris; Gandhi, Shivani

2018-01-01

The FDA's Presenting Risk Information draft guidance from May 2009 states that the time of risk versus benefit is a factor taken into consideration when evaluating audio and video direct-to-consumer (DTC) broadcasts. The objective of the study is to evaluate the proportion of risk narration on television (TV) advertisements in comparison to the actual proportion of serious adverse effects findings across select therapeutic areas. The study reviews prescription drug TV advertisements between the years 2010 and 2015 separated by therapeutic class. Indicators to assess risk versus benefit are as follows: total benefit time, total risk time, total ad time, percentage proportion of risk, and number of serious adverse effects (SAEs) listed in the package insert. The objective is establishing proportion of risk-to-benefit narration across therapeutic areas and the proportion of risk narration compared to the number of SAEs in the package insert. These outcomes will reflect whether TV advertisements abide by the "fair balance" rule and if the time spent on risk narrations is proportional to the number of SAEs across therapeutic areas. An analysis of risk versus benefit showed that there was a vast range of percentage differences in risk versus benefit narration across the products selected. The majority of the products narrated showed a 40% to 60% risk-to-benefit ratio. Six out of the 10 products evaluated communicated applicable black box warnings. There was variability among the SAE percentages presented between products. Lack of consistency exists between risks versus benefit proportions among different drug products.

Therapeutic hypothermia: applications in pediatric cardiac arrest.

PubMed

Kochanek, Patrick M; Fink, Ericka L; Bell, Michael J; Bayir, Hülya; Clark, Robert S B

2009-03-01

There is a rich history for the use of therapeutic hypothermia after cardiac arrest in neonatology and pediatrics. Laboratory reports date back to 1824 in experimental perinatal asphyxia. Similarly, clinical reports in pediatric cold water drowning victims represented key initiating work in the field. The application of therapeutic hypothermia in pediatric drowning victims represented some of the seminal clinical use of this modality in modern neurointensive care. Uncontrolled application (too deep and too long) and unique facets of asphyxial cardiac arrest in children (a very difficult insult to affect any benefit) likely combined to result in abandonment of therapeutic hypothermia in the mid to late 1980s. Important studies in perinatal medicine have built upon the landmark clinical trials in adults, and are once again bringing therapeutic hypothermia into standard care for pediatrics. Although more work is needed, particularly in the use of mild therapeutic hypothermia in children, there is a strong possibility that this important therapy will ultimately have broad applications after cardiac arrest and central nervous system (CNS) insults in the pediatric arena.

Possibility of Exosome-Based Therapeutics and Challenges in Production of Exosomes Eligible for Therapeutic Application.

PubMed

Yamashita, Takuma; Takahashi, Yuki; Takakura, Yoshinobu

2018-01-01

Exosomes are cell-derived vesicles with a diameter 30-120 nm. Exosomes contain endogenous proteins and nucleic acids; delivery of these molecules to exosome-recipient cells causes biological effects. Exosomes derived from some types of cells such as mesenchymal stem cells and dendritic cells have therapeutic potential and may be biocompatible and efficient agents against various disorders such as organ injury. However, there are many challenges for the development of exosome-based therapeutics. In particular, producing exosomal formulations is the major barrier for therapeutic application because of their heterogeneity and low productivity. Development and optimization of producing methods, including methods for isolation and storage of exosome formulations, are required for realizing exosome-based therapeutics. In addition, improvement of therapeutic potential and delivery efficiency of exosomes are important for their therapeutic application. In this review, we summarize current knowledge about therapeutic application of exosomes and discuss some challenges in their successful use.

Quantifying benefit-risk preferences for new medicines in rare disease patients and caregivers.

PubMed

Morel, T; Aymé, S; Cassiman, D; Simoens, S; Morgan, M; Vandebroek, M

2016-05-26

Rare disease patients and caregivers face uncommon, serious, debilitating conditions often characterised by poor prognosis and limited treatment options. This study aimed to explore what they consider of value when choosing between hypothetical therapeutic options and to quantify both their benefit-risk preferences and the influence of disease context. A mixed-methods survey with patients and caregivers was conducted in the United Kingdom across a range of rare diseases. Discrete-choice experiments that compared hypothetical treatment profiles of benefits and risks were used to measure respondent preferences across a set of seven attributes related to health outcomes, safety, and process of care. Bespoke questions on current disease management and the joint use of the 12-item WHODAS 2.0 questionnaire and of two Likert scales capturing self- and proxy-assessed disease-induced threat to life and impairment were implemented to describe disease context. Additionally, qualitative insights on the definitions of value and risk were collected from respondents. Final study sample included 721 patients and 152 informal caregivers, across 52 rare diseases. When choosing between hypothetical novel treatments for rare diseases, respondents attributed most importance to drug response, risk of serious side effects, and the ability to conduct usual activities while on treatment. In contrast, attributes related to treatment modalities were the least important. Respondents expressed a willingness to accept risks in hopes of finding some benefit, such as a higher chance of drug response or greater health improvement potential. Increasing disease severity, impairment or disability, and the lack of effective therapeutic options were shown to raise significantly the willingness to gain benefit through increased risk. This is the first study performing a quantitative discrete choice experiment amongst patients and caregivers across 52 rare conditions. It enables a more detailed

FGFR-targeted therapeutics for the treatment of breast cancer.

PubMed

De Luca, Antonella; Frezzetti, Daniela; Gallo, Marianna; Normanno, Nicola

2017-03-01

Breast cancer is a complex disease and several molecular drivers regulate its progression. Fibroblast growth factor receptor (FGFR) signaling is frequently deregulated in many cancers, including breast cancer. Due the involvement of the FGFR/FGF axis in the pathogenesis and progression of tumors, FGFR-targeted agents might represent a potential therapeutic option for breast cancer patients. Areas covered: This review offers an overview of targeted agents against FGFRs and their clinical development in breast cancer. The most relevant literature and the latest studies in the Clinicaltrial.com database have been discussed. Expert opinion: FGFR inhibition has been recently considered as a promising therapeutic option for different tumor types. However, preliminary results of clinical trials of FGFR inhibitors in breast cancer have been quite disappointing. In order to increase the clinical benefit of FGFR therapies in breast cancer, future studies should focus on: understanding the role of the various FGFR aberrations in cancer progression; identifying potential biomarkers to select patients that could benefit of FGFR inhibitors and developing therapeutic strategies that improve the efficacy of these agents and minimize toxicities.

TU-H-BRC-07: Therapeutic Benefit in Spatially Fractionated Radiotherapy (GRID) Using Helical Tomotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Narayanasamy, G; Zhang, X; Paudel, N

Purpose: The aim of this project is to study the therapeutic ratio (TR) for helical Tomotherapy (HT) based spatially fractionated radiotherapy (GRID). Estimation of TR was based on the linear-quadratic cell survival model by comparing the normal cell survival in a HT GRID to that of a uniform dose delivery in an open-field for the same tumor survival. Methods: HT GRID plan was generated using a patient specific virtual GRID block pattern of non-divergent, cylinder shaped holes using MLCs. TR was defined as the ratio of normal tissue surviving fraction (SF) under HT GRID irradiation to an open field irradiationmore » with an equivalent dose that result in the same tumor cell SF. The ratio was estimated from DVH data on ten patient plans with deep seated, bulky tumor approved by the treating radiation oncologist. Dependence of the TR values on radio-sensitivity of the tumor cells and prescription dose were also analyzed. Results: The mean ± standard deviation (SD) of TR was 4.0±0.7 (range: 3.1 to 5.5) for the 10 patients with single fraction dose of 20 Gy and tumor cell SF of 0.5 at 2 Gy. In addition, mean±SD of TR = 1±0.1 and 18.0±5.1 were found for tumor with SF of 0.3 and 0.7, respectively. Reducing the prescription dose to 15 and 10 Gy lowered the TR to 2.0±0.2 and 1.2±0.04 for a tumor cell SF of 0.5 at 2 Gy. In this study, the SF of normal cells was assumed to be 0.5 at 2 Gy. Conclusion: HT GRID displayed a significant therapeutic advantage over uniform dose from an open field irradiation. TR increases with the radioresistance of the tumor cells and with prescription dose.« less

WE-FG-BRA-05: Potential Clinical Benefit of LINAC Flattening-Filter-Free (FFF) Mode - Improvement of Treatment Therapeutic Ratio

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, S; Department of Biomedical Engineering, University of North Carolina- Chapel Hill/ North Carolina State University, Chapel Hill, North Carolina; Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC

Purpose: Ultrahigh dose-rate radiation at >40Gy/s has demonstrated astonishing normal-tissue sparing and tumor control in recent preclinical naive and tumor-bearing rodent studies when compared to the same radiation dose at a conventional dose-rate. The working mechanism of this fascinating dose-rate effect is currently under investigation. The aims of this work include investigating 1) whether LINAC FFF mode radiation at approximately 1Gy/s also has an improved therapeutic ratio compared to the same radiation dose at the conventional dose-rate of 0.05Gy/s, and 2) the dose-rate effect’s potential working mechanism by studying the expression of the P53 gene, linked to tumor suppression andmore » cell regulation after radiation damage. Methods: We used mouse model C57BL/6J, the same as that used in the ultrahigh dose-rate studies, and exposed them to total body irradiation (TBI) using the Elekta Versa accelerator 10MV photons. Mice (N=20) were given a total dose of 12Gy in both the high dose-rate group (n=10) using the FFF-mode and the conventional dose-rate group (n=10) using the conventional does rate mode. The FFF-mode treatment setup consisted of a 15cm×15cm field size setting at 53.2cm SSD while the conventional-mode set-up consisted of a 10cm×10cm field size at 100SSD. Post-radiation, animals were monitored daily for survival analysis and signs of moribundity requiring euthanasia. In addition, mouse spleens were harvested for P53 analysis at different time points. Results: For 12Gy TBI, the 1.3Gy/s FFF-mode high dose-rate produced a statistically significant (p=0.02) improvement in mouse survival compared to the 0.05Gy/s conventional dose-rate. An initial P53 study at the time of death time-point indicates that high dose-rate radiation induced a stronger expression of P53 than conventional dose-rate radiation. Conclusion: Our pilot study indicates that the FFF-mode high dose-rate radiation, which has been used largely to improve clinical throughput, may

Testing the effectiveness of family therapeutic assessment: a case study using a time-series design.

PubMed

Smith, Justin D; Wolf, Nicole J; Handler, Leonard; Nash, Michael R

2009-11-01

We describe a family Therapeutic Assessment (TA) case study employing 2 assessors, 2 assessment rooms, and a video link. In the study, we employed a daily measures time-series design with a pretreatment baseline and follow-up period to examine the family TA treatment model. In addition to being an illustrative addition to a number of clinical reports suggesting the efficacy of family TA, this study is the first to apply a case-based time-series design to test whether family TA leads to clinical improvement and also illustrates when that improvement occurs. Results support the trajectory of change proposed by Finn (2007), the TA model's creator, who posits that benefits continue beyond the formal treatment itself.

Potential Therapeutic Benefits of Green and Fermented Rooibos (Aspalathus linearis) in Dermal Wound Healing.

PubMed

Pringle, Nadine A; Koekemoer, Trevor C; Holzer, Andrea; Young, Carly; Venables, Luanne; van de Venter, Maryna

2018-02-28

The process of wound healing constitutes an ordered sequence of events that provides numerous opportunities for therapeutic intervention to improve wound repair. Rooibos, Aspalathus linearis , is a popular ingredient in skin care products, however, little scientific data exists exploring its therapeutic potential. In the present study, we evaluated the effects of fermented and aspalathin-enriched green rooibos in various in vitro models representative of dermal wound healing. Treatment of RAW 264.7 macrophages with fermented rooibos resulted in increased nitric oxide production as well as increased levels of cellular inducible nitric oxide synthase and cyclooxygenase-2, which are typical markers for classically activated macrophages. In contrast, the green extract was devoid of such activity. Using glycated gelatin as a model to mimic diabetic wounds, only the green extract showed potential to reduce cyclooxygenase-2 levels. Considering the role of reactive oxygen species in wound healing, the effects of rooibos on oxidative stress and cell death in human dermal fibroblasts was evaluated. Both fermented and green rooibos decreased cellular reactive oxygen species and attenuated apoptotic/necrotic cell death. Our findings highlight several properties that support the therapeutic potential of rooibos, and demonstrate that green and fermented rooibos present distinctly different properties with regards to their application in wound healing. The proinflammatory nature of fermented rooibos may have therapeutic value for wounds characterised with a delayed initial inflammatory phase, such as early diabetic wounds. The green extract is more suited to wounds burdened with excessive inflammation as it attenuated cyclooxygenase-2 levels and effectively protected fibroblasts against oxidative stress. Georg Thieme Verlag KG Stuttgart · New York.

The quartile benefit plot: a middle ear surgery benefit assessment scheme.

PubMed

Schmerber, Sébastien; Karkas, Alexandre; Righini, Christian A; Chahine, Karim A

2008-05-01

The purpose of this study is to present a new method for the assessment of hearing improvement following stapes surgery, taking into account additional, previously omitted evaluation criteria. Retrospective. A quartile plot, based on the currently used Glasgow benefit plot, is structured to include two additional criteria of hearing assessment, namely the absence of postoperative sensorineural hearing loss and the closure of the air-bone gap to <10 dB. Pre- and postoperative hearing results of 132 patients diagnosed with bilateral otosclerosis and treated with bilateral stapes surgery were plotted on both the classical Glasgow benefit plot and the new quartile benefit plot. The difference in success assessment due to stricter assessment criteria is demonstrated. Functional success rate following bilateral stapes surgery as plotted on the traditional Glasgow benefit plot was 51.5%. Success rate for bilateral stapes surgery assessed on the new quartile plot with the addition of the two new criteria was 38.64%. The difference in success rates was found to be statistically significant. The basis of benefit assessment in stapes surgery solely on the mean deficit in air conduction results in overestimation of success rate. This study demonstrates that results that appear satisfactory when judged by the Glasgow benefit plot are of modest success when assessed by the new quartile plot. The quartile benefit plot presented in this paper provides a strict measure of presentation and evaluation of stapes surgery results.

Resisting the therapeutic reduction: on the significance of sin.

PubMed

Delkeskamp-Hayes, Corinna

2007-01-01

Sin-talk, though politically incorrect, is indispensable. Placing human life under the "hermeneutic of sin" means acknowledging that one ought to aim flawlessly at God, and that one can fail in this endeavor. None of this can be appreciated within the contemporary post-Christian, mindset, which has attempted to reduce religion to morality and culture. In such a secular context, the guilt-feelings connected with the recognition of sin are considered to be harmful; the eternal benefit of a repentance is disregarded. Nevertheless, spirituality appears to have therapeutic benefits. Therefore attempts are made to re-locate within healthcare a religion shorn of its transcendent claims, so as then to harvest the benefits of a spirituality "saved from sin". This reduction of religiosity to its therapeutic function is nourished by a post-modern constructivist construal of religion. This article critically examines the dis-ingenuity marring such recasting, as well as the incoherence of related attempts to reduce transcendence to solidarity, and to re-shape the significance of religious rituals.

How collaboration in therapy becomes therapeutic: the therapeutic collaboration coding system.

PubMed

Ribeiro, Eugénia; Ribeiro, António P; Gonçalves, Miguel M; Horvath, Adam O; Stiles, William B

2013-09-01

The quality and strength of the therapeutic collaboration, the core of the alliance, is reliably associated with positive therapy outcomes. The urgent challenge for clinicians and researchers is constructing a conceptual framework to integrate the dialectical work that fosters collaboration, with a model of how clients make progress in therapy. We propose a conceptual account of how collaboration in therapy becomes therapeutic. In addition, we report on the construction of a coding system - the therapeutic collaboration coding system (TCCS) - designed to analyse and track on a moment-by-moment basis the interaction between therapist and client. Preliminary evidence is presented regarding the coding system's psychometric properties. The TCCS evaluates each speaking turn and assesses whether and how therapists are working within the client's therapeutic zone of proximal development, defined as the space between the client's actual therapeutic developmental level and their potential developmental level that can be reached in collaboration with the therapist. We applied the TCCS to five cases: a good and a poor outcome case of narrative therapy, a good and a poor outcome case of cognitive-behavioural therapy, and a dropout case of narrative therapy. The TCCS offers markers that may help researchers better understand the therapeutic collaboration on a moment-to-moment basis and may help therapists better regulate the relationship. © 2012 The British Psychological Society.

The potential therapeutic value for bereaved relatives participating in research: An exploratory study.

PubMed

Germain, Alison; Mayland, Catriona R; Jack, Barbara A

2016-10-01

Conducting research with the bereaved presents an immediate ethical challenge, as they are undoubtedly a vulnerable group, associated with high levels of distress and susceptible to both physical and mental health issues. A comprehensive understanding of the potential therapeutic benefits for bereaved relatives participating in palliative care research is limited, and therefore the ethics of engaging this group remain questionable. This paper describes a secondary analysis of qualitative data collected in the Care of the Dying Evaluation (CODE) project, examining the experiences of patients who died at home. It explores the motivations and potential benefits for bereaved relatives participating in research with reference to the recently developed concepts in bereavement theory. Cognitive interviews were conducted with 15 bereaved relatives and secondary analysis using a content analysis framework was employed to classify the data. The results center around six recurring concepts identified as adaptive in current bereavement theory: an opportunity to share the narrative accounts of the final hours of their relative's life; a search for sense and meaning in loss; an ongoing bond/attachment with the deceased; altruistic motivations; oscillation between loss and restorative orientations; and a sense of resilience. Overall, the participants found that taking part in the research was valuable and that it could be described as offering therapeutic benefits. The need for bereaved relatives to take part in research studies should be encouraged, as they provide an accurate proxy for the patient's experience of end-of-life care while also providing a valuable account of their own perspective as family member and carer. In addition, we highlight the need for ethics committees to be aware of the potential benefits for bereaved relatives participating in research of this kind.

Therapeutic misconception in clinical trials: fighting against it and living with it.

PubMed

Dal-Ré, R; Morell, F; Tejedor, J C; Gracia, D

2014-11-01

A clinical trial seeks information for the benefit of future patients and not necessarily for those who participate in the study. However, there are patients who believe that they will receive a direct therapeutic benefit by participating in a clinical trial, the so-called «therapeutic misconception». In this article, we describe the nature and extent of therapeutic misconception, which researchers can also experience. Its presence is especially important in phase 1 oncology trials and those with placebo group. To limit its occurrence, investigators have to ensure that participant information sheet are well written and to establish an effective and transparent discussion during the process of obtaining informed consent so that patients understand all aspects of their participation in the research and appreciate what this participation entails. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Patients' Experience of therapeutic footwear whilst living at risk of neuropathic diabetic foot ulceration: an interpretative phenomenological analysis (IPA).

PubMed

Paton, Joanne S; Roberts, Anne; Bruce, Graham K; Marsden, Jonathan

2014-02-22

Previous work has found that people with diabetes do not wear their therapeutic footwear as directed, but the thinking behind this behaviour is unclear. Adherence to therapeutic footwear advice must improve in order to reduce foot ulceration and amputation risk in people with diabetes and neuropathy. Therefore this study aimed to explore the psychological influences and personal experiences behind the daily footwear selection of individuals with diabetes and neuropathy. An interpretative phenomenological analysis (IPA) approach was used to explore the understanding and experience of therapeutic footwear use in people living at risk of diabetic neuropathic foot ulceration. This study benefited from the purposive selection of a small sample of four people and used in-depth semi structured interviews because it facilitated the deep and detailed examination of personal thoughts and feelings behind footwear selection. Four overlapping themes that interact to regulate footwear choice emerged from the analyses: a) Self-perception dilemma; resolving the balance of risk experienced by people with diabetes and neuropathy day to day, between choosing to wear footwear to look and feel normal and choosing footwear to protect their feet from foot ulceration; b) Reflective adaption; The modification and individualisation of a set of values about footwear usage created in the minds of people with diabetes and neuropathy; c) Adherence response; The realignment of footwear choice with personal values, to reinforce the decision not to change behaviour or bring about increased footwear adherence, with or without appearance management; d) Reality appraisal; A here and now appraisal of the personal benefit of footwear choice on emotional and physical wellbeing, with additional consideration to the preservation of therapeutic footwear. For some people living at risk of diabetic neuropathic foot ulceration, the decision whether or not to wear therapeutic footwear is driven by the

Patients’ Experience of therapeutic footwear whilst living at risk of neuropathic diabetic foot ulceration: an interpretative phenomenological analysis (IPA)

PubMed Central

2014-01-01

Background Previous work has found that people with diabetes do not wear their therapeutic footwear as directed, but the thinking behind this behaviour is unclear. Adherence to therapeutic footwear advice must improve in order to reduce foot ulceration and amputation risk in people with diabetes and neuropathy. Therefore this study aimed to explore the psychological influences and personal experiences behind the daily footwear selection of individuals with diabetes and neuropathy. Methods An interpretative phenomenological analysis (IPA) approach was used to explore the understanding and experience of therapeutic footwear use in people living at risk of diabetic neuropathic foot ulceration. This study benefited from the purposive selection of a small sample of four people and used in-depth semi structured interviews because it facilitated the deep and detailed examination of personal thoughts and feelings behind footwear selection. Findings Four overlapping themes that interact to regulate footwear choice emerged from the analyses: a) Self-perception dilemma; resolving the balance of risk experienced by people with diabetes and neuropathy day to day, between choosing to wear footwear to look and feel normal and choosing footwear to protect their feet from foot ulceration; b) Reflective adaption; The modification and individualisation of a set of values about footwear usage created in the minds of people with diabetes and neuropathy; c) Adherence response; The realignment of footwear choice with personal values, to reinforce the decision not to change behaviour or bring about increased footwear adherence, with or without appearance management; d) Reality appraisal; A here and now appraisal of the personal benefit of footwear choice on emotional and physical wellbeing, with additional consideration to the preservation of therapeutic footwear. Conclusion For some people living at risk of diabetic neuropathic foot ulceration, the decision whether or not to wear

Armed Therapeutic Viruses – A Disruptive Therapy on the Horizon of Cancer Immunotherapy

PubMed Central

Bauzon, Maxine; Hermiston, Terry

2014-01-01

For the past 150 years cancer immunotherapy has been largely a theoretical hope that recently has begun to show potential as a highly impactful treatment for various cancers. In particular, the identification and targeting of immune checkpoints have given rise to exciting data suggesting that this strategy has the potential to activate sustained antitumor immunity. It is likely that this approach, like other anti-cancer strategies before it, will benefit from co-administration with an additional therapeutic and that it is this combination therapy that may generate the greatest clinical outcome for the patient. In this regard, oncolytic viruses are a therapeutic moiety that is well suited to deliver and augment these immune-modulating therapies in a highly targeted and economically advantageous way over current treatment. In this review, we discuss the blockade of immune checkpoints, how oncolytic viruses complement and extend these therapies, and speculate on how this combination will uniquely impact the future of cancer immunotherapy. PMID:24605114

Therapeutic potential of cannabis-related drugs.

PubMed

Alexander, Stephen P H

2016-01-04

In this review, I will consider the dual nature of Cannabis and cannabinoids. The duality arises from the potential and actuality of cannabinoids in the laboratory and clinic and the 'abuse' of Cannabis outside the clinic. The therapeutic areas currently best associated with exploitation of Cannabis-related medicines include pain, epilepsy, feeding disorders, multiple sclerosis and glaucoma. As with every other medicinal drug of course, the 'trick' will be to maximise the benefit and minimise the cost. After millennia of proximity and exploitation of the Cannabis plant, we are still playing catch up with an understanding of its potential influence for medicinal benefit. Copyright © 2015 Elsevier Inc. All rights reserved.

Computational Fluid Dynamics and Additive Manufacturing to Diagnose and Treat Cardiovascular Disease.

PubMed

Randles, Amanda; Frakes, David H; Leopold, Jane A

2017-11-01

Noninvasive engineering models are now being used for diagnosing and planning the treatment of cardiovascular disease. Techniques in computational modeling and additive manufacturing have matured concurrently, and results from simulations can inform and enable the design and optimization of therapeutic devices and treatment strategies. The emerging synergy between large-scale simulations and 3D printing is having a two-fold benefit: first, 3D printing can be used to validate the complex simulations, and second, the flow models can be used to improve treatment planning for cardiovascular disease. In this review, we summarize and discuss recent methods and findings for leveraging advances in both additive manufacturing and patient-specific computational modeling, with an emphasis on new directions in these fields and remaining open questions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Future therapeutic directions; new medications and insulin delivery in a changing world for effective diabetes management.

PubMed

Modi, Pankaj

2009-09-01

Insulin remains a key to the management of diabetes. The early addition of insulin to oral therapy in type-2 patients is recognized as an effective option that can help improve glycemic control and reduces the complications and contribute to more favorable outcomes. Controlling blood glucose levels within acceptable limits is crucial to the long-term health of patients with diabetes. The benefits of patient education and chronic disease management tools cannot be underestimated as many patients will require education and help in initiation of insulin therapy to achieve glycemic targets. The wide choice of insulin formulations and the ever-expanding range of delivery methods are now available. These methods made insulin administration easier, less painful, more discreet, and more accurate than ever before thus providing important tools to overcome barriers to insulin initiation and improve achievement of glycemic goals. In addition, exciting developments in newer therapeutics have increased the potential for optimal glycemic control. This review discusses how these approaches can help patients manage their diabetes effectively by considering new insulin formulations and delivery devices and newer therapeutics.

Therapeutic singing as an early intervention for swallowing in persons with Parkinson's disease.

PubMed

Stegemöller, E L; Hibbing, P; Radig, H; Wingate, J

2017-04-01

For persons with Parkinson's disease (PD), secondary motor symptoms such as swallow impairment impact the quality of life and are major contributors to mortality. There is a present need for therapeutic interventions aimed at improving swallow function during the early stages of PD. The purpose of this pilot study was to examine the effects of a group therapeutic singing intervention on swallowing in persons with PD with no significant dysphagia symptoms. Cohort study. University in the United States. Twenty-four participants with PD. Eight weeks of group therapeutic singing. Electromyography (EMG) was used to assess muscle activity associated with swallow pre and post the group singing intervention. Swallow quality of life (SWAL-QOL) and the Unified Parkinson's Disease Rating Scale (UPDRS) were also obtained pre- and post-intervention. Participants reported minimal difficulty with swallowing, yet results revealed a significant increase in EMG outcome measures, as well as significant improvement in UPDRS total and UPDRS motor scores. No significant differences were revealed for SWAL-QOL. Increases in EMG timing measures may suggest that group singing results in the prolongation of laryngeal elevation, protecting the airway from foreign material for longer periods of time during swallow. Combined with the improvement in UPDRS clinical measures, therapeutic singing may be an engaging early intervention strategy to address oropharyngeal dysphagia while also benefiting additional clinical symptoms of PD. Copyright © 2017 Elsevier Ltd. All rights reserved.

The population benefit of evidence-based radiotherapy: 5-Year local control and overall survival benefits.

PubMed

Hanna, T P; Shafiq, J; Delaney, G P; Vinod, S K; Thompson, S R; Barton, M B

2018-02-01

To describe the population benefit of radiotherapy in a high-income setting if evidence-based guidelines were routinely followed. Australian decision tree models were utilized. Radiotherapy alone (RT) benefit was defined as the absolute proportional benefit of radiotherapy compared with no treatment for radical indications, and of radiotherapy over surgery alone for adjuvant indications. Chemoradiotherapy (CRT) benefit was the absolute incremental benefit of concurrent chemoradiotherapy over RT. Five-year local control (LC) and overall survival (OS) benefits were measured. Citation databases were systematically queried for benefit data. Meta-analysis and sensitivity analysis were performed. 48% of all cancer patients have indications for radiotherapy, 34% curative and 14% palliative. RT provides 5-year LC benefit in 10.4% of all cancer patients (95% Confidence Interval 9.3, 11.8) and 5-year OS benefit in 2.4% (2.1, 2.7). CRT provides 5-year LC benefit in an additional 0.6% of all cancer patients (0.5, 0.6), and 5-year OS benefit for an additional 0.3% (0.2, 0.4). RT benefit was greatest for head and neck (LC 32%, OS 16%), and cervix (LC 33%, OS 18%). CRT LC benefit was greatest for rectum (6%) and OS for cervix (3%) and brain (3%). Sensitivity analysis confirmed a robust model. Radiotherapy provides significant 5-year LC and OS benefits as part of evidence-based cancer care. CRT provides modest additional benefits. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Therapeutic Hypothermia in Spinal Cord Injury: The Status of Its Use and Open Questions.

PubMed

Wang, Jiaqiong; Pearse, Damien D

2015-07-24

Spinal cord injury (SCI) is a major health problem and is associated with a diversity of neurological symptoms. Pathophysiologically, dysfunction after SCI results from the culmination of tissue damage produced both by the primary insult and a range of secondary injury mechanisms. The application of hypothermia has been demonstrated to be neuroprotective after SCI in both experimental and human studies. The myriad of protective mechanisms of hypothermia include the slowing down of metabolism, decreasing free radical generation, inhibiting excitotoxicity and apoptosis, ameliorating inflammation, preserving the blood spinal cord barrier, inhibiting astrogliosis, promoting angiogenesis, as well as decreasing axonal damage and encouraging neurogenesis. Hypothermia has also been combined with other interventions, such as antioxidants, anesthetics, alkalinization and cell transplantation for additional benefit. Although a large body of work has reported on the effectiveness of hypothermia as a neuroprotective approach after SCI and its application has been translated to the clinic, a number of questions still remain regarding its use, including the identification of hypothermia's therapeutic window, optimal duration and the most appropriate rewarming rate. In addition, it is necessary to investigate the neuroprotective effect of combining therapeutic hypothermia with other treatment strategies for putative synergies, particularly those involving neurorepair.

Outcomes and benefits of pediatric cochlear implantation in children with additional disabilities: a review and report of family influences on outcomes.

PubMed

Cejas, Ivette; Hoffman, Michael F; Quittner, Alexandra L

2015-01-01

The number of children with hearing loss with additional disabilities receiving cochlear implantation has increased dramatically over the past decade. However, little is known about their auditory and speech and language development following implantation. The purpose of this review is to evaluate the effects of cochlear implantation on the most common genetic and developmental disorders in children with hearing loss. Benefits of cochlear implantation for children with autism spectrum disorder, developmental delay, CHARGE syndrome, cerebral palsy, learning disorders, Usher syndrome, Waardenburg syndrome, and attention deficit/hyperactivity disorder are reviewed. Our review indicates that children with hearing loss and additional disabilities benefit from cochlear implantation, especially when implanted early. Thus, early interventions seem as important for these children as for deaf children without additional disabilities. Comparisons of outcomes across these disabilities indicate that children with little to no cognitive impairment (eg, Waardenburg sydrome, attention deficit hyperactivity disorder) have better outcomes than those with greater deficits in intellectual functioning (eg, autism, CHARGE syndrome). In addition, parents of children with hearing loss and additional disabilities report higher levels of parenting stress and greater child behavior problems than those without comorbid diagnoses. However, these parents are as sensitive when interacting with their children as parents with typically developing children using cochlear implantation. Given these results, it is critical to evaluate these children's developmental milestones to provide early implantation and intervention, appropriately counsel families regarding realistic expectations for the implant, and facilitate family adaptation.

Outcomes and benefits of pediatric cochlear implantation in children with additional disabilities: a review and report of family influences on outcomes

PubMed Central

Cejas, Ivette; Hoffman, Michael F; Quittner, Alexandra L

2015-01-01

The number of children with hearing loss with additional disabilities receiving cochlear implantation has increased dramatically over the past decade. However, little is known about their auditory and speech and language development following implantation. The purpose of this review is to evaluate the effects of cochlear implantation on the most common genetic and developmental disorders in children with hearing loss. Benefits of cochlear implantation for children with autism spectrum disorder, developmental delay, CHARGE syndrome, cerebral palsy, learning disorders, Usher syndrome, Waardenburg syndrome, and attention deficit/hyperactivity disorder are reviewed. Our review indicates that children with hearing loss and additional disabilities benefit from cochlear implantation, especially when implanted early. Thus, early interventions seem as important for these children as for deaf children without additional disabilities. Comparisons of outcomes across these disabilities indicate that children with little to no cognitive impairment (eg, Waardenburg sydrome, attention deficit hyperactivity disorder) have better outcomes than those with greater deficits in intellectual functioning (eg, autism, CHARGE syndrome). In addition, parents of children with hearing loss and additional disabilities report higher levels of parenting stress and greater child behavior problems than those without comorbid diagnoses. However, these parents are as sensitive when interacting with their children as parents with typically developing children using cochlear implantation. Given these results, it is critical to evaluate these children’s developmental milestones to provide early implantation and intervention, appropriately counsel families regarding realistic expectations for the implant, and facilitate family adaptation. PMID:29388595

Meditation as a Therapeutic Intervention for Adults at Risk for Alzheimer’s Disease – Potential Benefits and Underlying Mechanisms

PubMed Central

Innes, Kim E.; Selfe, Terry Kit

2014-01-01

Alzheimer’s disease (AD) is a chronic, progressive, brain disorder that affects at least 5.3 million Americans at an estimated cost of $148 billion, figures that are expected to rise steeply in coming years. Despite decades of research, there is still no cure for AD, and effective therapies for preventing or slowing progression of cognitive decline in at-risk populations remain elusive. Although the etiology of AD remains uncertain, chronic stress, sleep deficits, and mood disturbance, conditions common in those with cognitive impairment, have been prospectively linked to the development and progression of both chronic illness and memory loss and are significant predictors of AD. Therapies such as meditation that specifically target these risk factors may thus hold promise for slowing and possibly preventing cognitive decline in those at risk. In this study, we briefly review the existing evidence regarding the potential utility of meditation as a therapeutic intervention for those with and at risk for AD, discuss possible mechanisms underlying the observed benefits of meditation, and outline directions for future research. PMID:24795656

Transdermal delivery of therapeutic agent

NASA Technical Reports Server (NTRS)

Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

2008-01-01

A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

Employing the therapeutic operating characteristic (TOC) graph for individualised dose prescription.

PubMed

Hoffmann, Aswin L; Huizenga, Henk; Kaanders, Johannes H A M

2013-03-07

In current practice, patients scheduled for radiotherapy are treated according to 'rigid' protocols with predefined dose prescriptions that do not consider risk-taking preferences of individuals. The therapeutic operating characteristic (TOC) graph is applied as a decision-aid to assess the trade-off between treatment benefit and morbidity to facilitate dose prescription customisation. Historical dose-response data from prostate cancer patient cohorts treated with 3D-conformal radiotherapy is used to construct TOC graphs. Next, intensity-modulated (IMRT) plans are generated by optimisation based on dosimetric criteria and dose-response relationships. TOC graphs are constructed for dose-scaling of the optimised IMRT plan and individualised dose prescription. The area under the TOC curve (AUC) is estimated to measure the therapeutic power of these plans. On a continuous scale, the TOC graph directly visualises treatment benefit and morbidity risk of physicians' or patients' choices for dose (de-)escalation. The trade-off between these probabilities facilitates the selection of an individualised dose prescription. TOC graphs show broader therapeutic window and higher AUCs with increasing target dose heterogeneity. The TOC graph gives patients and physicians access to a decision-aid and read-out of the trade-off between treatment benefit and morbidity risks for individualised dose prescription customisation over a continuous range of dose levels.

A comparison of the additional protocols of the five nuclear weapon states and the ensuing safeguards benefits to international nonproliferation efforts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uribe, Eva C; Sandoval, M Analisa; Sandoval, Marisa N

2009-01-01

With the 6 January 2009 entry into force of the Additional Protocol by the United States of America, all five declared Nuclear Weapon States that are part of the Nonproliferation Treaty have signed, ratified, and put into force the Additional Protocol. This paper makes a comparison of the strengths and weaknesses of the five Additional Protocols in force by the five Nuclear Weapon States with respect to the benefits to international nonproliferation aims. This paper also documents the added safeguards burden to the five declared Nuclear Weapon States that these Additional Protocols put on the states with respect to accessmore » to their civilian nuclear programs and the hosting of complementary access activities as part of the Additional Protocol.« less

Therapeutic Effects of Phytochemicals and Medicinal Herbs on Depression

PubMed Central

2017-01-01

Background. Depression is a recurrent, common, and potentially life-threatening psychiatric disease related to multiple assignable causes. Although conventional antidepressant therapy can help relieve symptoms of depression and prevent relapse of the illness, complementary therapies are required due to disadvantage of the current therapy such as adverse effects. Moreover, a number of studies have researched adjunctive therapeutic approaches to improve outcomes for depression patients. Purpose. One potential complementary method with conventional antidepressants involves the use of medicinal herbs and phytochemicals that provide therapeutic benefits. Studies have revealed beneficial effects of medical herbs and phytochemicals on depression and their central nervous system mechanism. Here, we summarize the current knowledge of the therapeutic benefits of phytochemicals and medicinal herbs against depression and describe their detailed mechanisms. Sections. There are two sections, phytochemicals against depression and medical herbs against depression, in this review. Conclusion. Use of phytomedicine may be an alternative option for the treatment of depression in case conventional drugs are not applicable due to their side effects, low effectiveness, or inaccessibility. However, the efficacy and safety of these phytomedicine treatments for depression have to be supported by clinical studies. PMID:28503571

Therapeutic Effects of Phytochemicals and Medicinal Herbs on Depression.

PubMed

Lee, Gihyun; Bae, Hyunsu

2017-01-01

Background . Depression is a recurrent, common, and potentially life-threatening psychiatric disease related to multiple assignable causes. Although conventional antidepressant therapy can help relieve symptoms of depression and prevent relapse of the illness, complementary therapies are required due to disadvantage of the current therapy such as adverse effects. Moreover, a number of studies have researched adjunctive therapeutic approaches to improve outcomes for depression patients. Purpose . One potential complementary method with conventional antidepressants involves the use of medicinal herbs and phytochemicals that provide therapeutic benefits. Studies have revealed beneficial effects of medical herbs and phytochemicals on depression and their central nervous system mechanism. Here, we summarize the current knowledge of the therapeutic benefits of phytochemicals and medicinal herbs against depression and describe their detailed mechanisms. Sections . There are two sections, phytochemicals against depression and medical herbs against depression, in this review. Conclusion . Use of phytomedicine may be an alternative option for the treatment of depression in case conventional drugs are not applicable due to their side effects, low effectiveness, or inaccessibility. However, the efficacy and safety of these phytomedicine treatments for depression have to be supported by clinical studies.

Effects of language concordance and interpreter use on therapeutic alliance in Spanish-speaking integrated behavioral health care patients.

PubMed

Villalobos, Bianca T; Bridges, Ana J; Anastasia, Elizabeth A; Ojeda, Carlos A; Rodriguez, Juventino Hernandez; Gomez, Debbie

2016-02-01

The discrepancy between the growing number of Spanish speakers in the U.S. and the availability of bilingual providers creates a barrier to accessing quality mental health care. Use of interpreters provides one strategy for overcoming this linguistic barrier; however, concerns about whether sessions with interpreters, versus bilingual providers, impede therapeutic alliance remain. The current study explored associations between the use of interpreters and therapeutic alliance in a sample of 458 Spanish-speaking patients seen for integrated behavioral health visits at primary care clinics. Patients completed a brief (4 item) therapeutic alliance scale at their behavioral health appointment. In addition, to supplement the quantitative study data, a pilot study of 30 qualitative interviews was conducted with a new sample of 10 Spanish-speaking patients, 10 behavioral health consultants (BHCs), and 10 trained interpreters. Quantitative results showed that interpreter use did not relate to therapeutic alliance, even when controlling for relevant demographic variables. However, qualitative interviews suggested major themes regarding the relative benefits and challenges of using interpreters for patients, interpreters, and BHCs. In interviews, patients expressed a strong preference for bilingual providers. Benefits included greater privacy, sense of trust, and accuracy of communication. However, in their absence, interpreters were seen as increasing access to services and facilitating communication with providers, thereby addressing the behavioral health needs of patients with limited English proficiency. BHCs and interpreters emphasized the importance of interpreter training and a good collaborative relationship with interpreters to minimize negative effects on the quality of care. (c) 2016 APA, all rights reserved).

Three methods for integration of environmental risk into the benefit-risk assessment of veterinary medicinal products.

PubMed

Chapman, Jennifer L; Porsch, Lucas; Vidaurre, Rodrigo; Backhaus, Thomas; Sinclair, Chris; Jones, Glyn; Boxall, Alistair B A

2017-12-15

Veterinary medicinal products (VMPs) require, as part of the European Union (EU) authorization process, consideration of both risks and benefits. Uses of VMPs have multiple risks (e.g., risks to the animal being treated, to the person administering the VMP) including risks to the environment. Environmental risks are not directly comparable to therapeutic benefits; there is no standardized approach to compare both environmental risks and therapeutic benefits. We have developed three methods for communicating and comparing therapeutic benefits and environmental risks for the benefit-risk assessment that supports the EU authorization process. Two of these methods support independent product evaluation (i.e., a summative classification and a visual scoring matrix classification); the other supports a comparative evaluation between alternative products (i.e., a comparative classification). The methods and the challenges to implementing a benefit-risk assessment including environmental risk are presented herein; how these concepts would work in current policy is discussed. Adaptability to scientific and policy development is considered. This work is an initial step in the development of a standardized methodology for integrated decision-making for VMPs. Copyright © 2017 Elsevier B.V. All rights reserved.

Health benefits of anthocyanins and molecular mechanisms: Update from recent decade.

PubMed

Li, Daotong; Wang, Pengpu; Luo, Yinghua; Zhao, Mengyao; Chen, Fang

2017-05-24

Anthocyanins are one of the most widespread families of natural pigments in the plant kingdom. Their health beneficial effects have been documented in many in vivo and in vitro studies. This review summarizes the most recent literature regarding the health benefits of anthocyanins and their molecular mechanisms. It appears that several signaling pathways, including mitogen-activated protein kinase, nuclear factor κB, AMP-activated protein kinase, and Wnt/β-catenin, as well as some crucial cellular processes, such as cell cycle, apoptosis, autophagy, and biochemical metabolism, are involved in these beneficial effects and may provide potential therapeutic targets and strategies for the improvement of a wide range of diseases in future. In addition, specific anthocyanin metabolites contributing to the observed in vivo biological activities, structure-activity relationships as well as additive and synergistic efficacy of anthocyanins are also discussed.

Therapeutic potential of abalone and status of bioactive molecules: A comprehensive review.

PubMed

Suleria, H A R; Masci, P P; Gobe, G C; Osborne, S A

2017-05-24

Marine organisms are increasingly being investigated as sources of bioactive molecules with therapeutic applications as nutraceuticals and pharmaceuticals. In particular, nutraceuticals are gaining popularity worldwide owing to their therapeutic potential and incorporation in functional foods and dietary supplements. Abalone, a marine gastropod, contains a variety of bioactive compounds with anti-oxidant, anti-thrombotic, anti-inflammatory, anti-microbial, and anti-cancer activities. For thousands of years different cultures have used abalone as a traditional functional food believing consumption provides health benefits. Abalone meat is one of the most precious commodities in Asian markets where it is considered a culinary delicacy. Recent research has revealed that abalone is composed of many vital moieties like polysaccharides, proteins, and fatty acids that provide health benefits beyond basic nutrition. A review of past and present research is presented with relevance to the therapeutic potential of bioactive molecules from abalone.

Therapeutics incorporating blood constituents.

PubMed

Charoenphol, Phapanin; Oswalt, Katie; Bishop, Corey J

2018-04-05

Blood deficiency and dysfunctionality can result in adverse events, which can primarily be treated by transfusion of blood or the re-introduction of properly functioning sub-components. Blood constituents can be engineered on the sub-cellular (i.e., DNA recombinant technology) and cellular level (i.e., cellular hitchhiking for drug delivery) for supplementing and enhancing therapeutic efficacy, in addition to rectifying dysfunctioning mechanisms (i.e., clotting). Herein, we report the progress of blood-based therapeutics, with an emphasis on recent applications of blood transfusion, blood cell-based therapies and biomimetic carriers. Clinically translated technologies and commercial products of blood-based therapeutics are subsequently highlighted and perspectives on challenges and future prospects are discussed. Blood-based therapeutics is a burgeoning field and has advanced considerably in recent years. Blood and its constituents, with and without modification (i.e., combinatorial), have been utilized in a broad spectrum of pre-clinical and clinically-translated treatments. This review article summarizes the most up-to-date progress of blood-based therapeutics in the following contexts: synthetic blood substitutes, acellular/non-recombinant therapies, cell-based therapies, and therapeutic sub-components. The article subsequently discusses clinically-translated technologies and future prospects thereof. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Society already achieves economic benefits from generic substitution but fails to do the same for therapeutic substitution.

PubMed

Gumbs, Pearl D; Verschuren, W M Monique; Souverein, Patrick C; Mantel-Teeuwisse, Aukje K; de Wit, G Ardine; de Boer, Anthonius; Klungel, Olaf H

2007-11-01

To assess the potential annual savings due to generic and therapeutic substitution of statin therapy for the general Dutch population, taking the patients medical history into account. We conducted a population-based costing study using the PHARMO Record Linkage System (RLS). PHARMO RLS contains drug dispensing records from a representative sample of pharmacies located in more than 50 regions in the Netherlands. We selected all statin users in the database since 2003. The cost-savings of generic substitution of statin therapy for all simvastatin and pravastatin users, and of therapeutic substitution of statin therapy for other statin users were calculated. Substituting current users and new users of statins were considered separately. Therapeutic substitution was based on the medical history of the individual patient. Patients were only substituted if there was an appropriate substitute available. The appropriateness of substitution was based on drug-drug interactions between statins and possible comedication and the availability of an equipotent alternative. Substituting (generic and therapeutic) statin therapy for all current users would lead to potential annual savings of approximately 87 million euros. Substituting (generic and therapeutic) all starters on statin therapy would lead to potential annual savings of around 51 million euros. In the case of generic substitution only, the potential annual savings for all current simvastatin and pravastatin users would be 2.4 million euros and for the new users about 1.8 million euros. From an economic point of view, society could gain a lot from substituting statin therapy, especially from therapeutic substitution.

Therapeutic efficacy of equine botulism antitoxin in Rhesus macaques

PubMed Central

Emanuel, Andrew; Takla, Teresa; Hua, Yi; Hobbs, Charles; LeClaire, Ross; O’Donnell, Denise C.

2017-01-01

Background There are currently no licensed vaccines available for prevention of botulism in humans. The vaccination is not desirable due to expanding therapeutic indications of botulinum toxins. The only available specific treatment for botulism is antitoxin to remove circulating toxin, thus, preventing further neuronal damage. BAT® (Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)—(Equine)) has been developed and its therapeutic efficacy evaluated against botulinum neurotoxin serotype A (BoNT/A) in Rhesus macaques. Methods and findings In a post-exposure prophylaxis (PEP) study, animals were exposed to 4x LD50/kg of BoNT/A and administered intravenously with either BAT (1x or 0.1x scaled human dose), or placebo at 4 hours post-exposure. The animals were monitored for 14 days. For the therapeutic intervention studies, animals were exposed to a 1.7x LD50/kg of BoNT/A and treated intravenously with either placebo or BAT at a 1x scaled human dose at the onset of clinical signs. Animals were monitored on an hourly basis for 14 or 21 days. In the PEP study, all animals tolerated equine based antitoxin without any adverse clinical signs. A 100% survival was observed in groups treated with the BAT compared to 0% survival in those treated with the placebo (p<0.001, Fisher’s exact test). BAT antitoxin prevented the development of signs of neurotoxicity of botulinum toxin. In a therapeutic study, treatment with the BAT at scaled 1x human dose after the onset of clinical signs significantly enhanced survival compared to the placebo (46.6% vs. 0%, p<0.0001, Fisher’s exact test). Additionally, treatment with the BAT delayed the progression of signs (muscular weakness, respiratory distress, oral/nasal discharge) of toxin intoxication and reduced the severity of the disease. Conclusions A single dose of BAT, when administered to symptomatic monkeys, resulted in a statistically significant survival benefit compared to the placebo. Additionally, BAT completely protected

Therapeutic efficacy of equine botulism antitoxin in Rhesus macaques.

PubMed

Kodihalli, Shantha; Emanuel, Andrew; Takla, Teresa; Hua, Yi; Hobbs, Charles; LeClaire, Ross; O'Donnell, Denise C

2017-01-01

There are currently no licensed vaccines available for prevention of botulism in humans. The vaccination is not desirable due to expanding therapeutic indications of botulinum toxins. The only available specific treatment for botulism is antitoxin to remove circulating toxin, thus, preventing further neuronal damage. BAT® (Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)-(Equine)) has been developed and its therapeutic efficacy evaluated against botulinum neurotoxin serotype A (BoNT/A) in Rhesus macaques. In a post-exposure prophylaxis (PEP) study, animals were exposed to 4x LD50/kg of BoNT/A and administered intravenously with either BAT (1x or 0.1x scaled human dose), or placebo at 4 hours post-exposure. The animals were monitored for 14 days. For the therapeutic intervention studies, animals were exposed to a 1.7x LD50/kg of BoNT/A and treated intravenously with either placebo or BAT at a 1x scaled human dose at the onset of clinical signs. Animals were monitored on an hourly basis for 14 or 21 days. In the PEP study, all animals tolerated equine based antitoxin without any adverse clinical signs. A 100% survival was observed in groups treated with the BAT compared to 0% survival in those treated with the placebo (p<0.001, Fisher's exact test). BAT antitoxin prevented the development of signs of neurotoxicity of botulinum toxin. In a therapeutic study, treatment with the BAT at scaled 1x human dose after the onset of clinical signs significantly enhanced survival compared to the placebo (46.6% vs. 0%, p<0.0001, Fisher's exact test). Additionally, treatment with the BAT delayed the progression of signs (muscular weakness, respiratory distress, oral/nasal discharge) of toxin intoxication and reduced the severity of the disease. A single dose of BAT, when administered to symptomatic monkeys, resulted in a statistically significant survival benefit compared to the placebo. Additionally, BAT completely protected monkeys from the clinical signs of intoxication

The central nervous system--an additional consideration in 'rotator cuff tendinopathy' and a potential basis for understanding response to loaded therapeutic exercise.

PubMed

Littlewood, Chris; Malliaras, Peter; Bateman, Marcus; Stace, Richmond; May, Stephen; Walters, Stephen

2013-12-01

Tendinopathy is a term used to describe a painful tendon disorder but despite being a well-recognised clinical presentation, a definitive understanding of the pathoaetiology of rotator cuff tendinopathy remains elusive. Current explanatory models, which relate to peripherally driven nocioceptive mechanisms secondary to structural abnormality, or failed healing, appear inadequate on their own in the context of current literature. In light of these limitations this paper presents an extension to current models that incorporates the integral role of the central nervous system in the pain experience. The role of the central nervous system (CNS) is described and justified along with a potential rationale to explain the favourable response to loaded therapeutic exercises demonstrated by previous studies. This additional consideration has the potential to offer a useful way to explain pain to patients, for clinicians to prescribe appropriate therapeutic management strategies and for researchers to advance knowledge in relation to this clinically challenging problem. Copyright © 2013 Elsevier Ltd. All rights reserved.

The best of both worlds: reaping the benefits from mammalian and bacterial therapeutic circuits.

PubMed

Bojar, Daniel; Fussenegger, Martin

2016-10-01

Synthetic biology has revolutionized the field of biology in the last two decades. By taking apart natural systems and recombining engineered parts in novel constellations, it has not only unlocked a staggering variety of biological control mechanisms but it has also created a panoply of biomedical achievements, such as innovative diagnostics and therapies. The most common mode of action in the field of synthetic biology is mediated by synthetic gene circuits assembled in a systematic and rational manner. This review covers the most recent therapeutic gene circuits implemented in mammalian and bacterial cells designed for the diagnosis and therapy of an extensive array of diseases. Highlighting new tools for therapeutic gene circuits, we describe a future that holds a plethora of potentialities for the medicine of tomorrow. Copyright © 2016 Elsevier Ltd. All rights reserved.

Therapeutic experiences of community gardens: putting flow in its place.

PubMed

Pitt, Hannah

2014-05-01

This paper develops the concept of therapeutic place experiences by considering the role of activity. Research of community gardening finds that particular tasks are therapeutic and exhibit the characteristics of flow, but those who lack influence over their community gardening are less likely to benefit from flow as their sense of control is reduced. The notion of emplaced flow is proposed to locate individual experiences amongst socio-spatial factors which limit self-determinacy and therefore affect wellbeing. Emplacing flow prompts critical reflection on who is excluded from therapeutic place experiences, and whether sites offering momentary escape have an enduring impact on wellbeing. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cost-Benefit Analysis of Internet Therapeutic Intervention on Patients With Diabetes

PubMed Central

Deng, Lan; White, Adam S.; Pawlowska, Monika; Pottinger, Betty; Aydin, Jessica; Chow, Nelson; Tildesley, Hugh D.

2015-01-01

Background: With the emergence of IBGMS for allowing for patients to communicate their self-monitored blood glucose (SMBG) readings with their health care providers, their impact on the management of diabetes is becoming well-supported with regards to clinical benefits. Their impact on healthcare costs, however, has yet to be investigated. This study aims to determine the cost-benefits of such interventions in comparison to routine care. Objectives: To analyze the cost-benefit of an Internet Blood Glucose Monitoring Service (IBGMS) in comparison to routine diabetes care. Patients and Methods: 200 patients were surveyed to assess the cost associated with doctor appointments in the past 12 months. Annual number of visits to medical services for diabetes and costs of transportation, parking, and time taken off work for visits were surveyed. Self-reported frequency of SMBG and most recent A1C were also surveyed. We compared 100 patients who used the IBGMS with 100 patients who only used routine care. Results: There is a trend of lowered total cost in the intervention group compared to the control group. The control group spent $210.89 per year on visits to physicians; the intervention group spent $131.26 (P = 0.128). Patients in control group visited their endocrinologist 1.76 times per year, those in intervention group visited their endocrinologist 1.36 times per year, significantly less frequently than the control group (P = 0.014). Number of visits to other medical services is similar between the groups. Average A1C in intervention group is 7.57%, in control group is 7.69% (P = 0.309). Conclusions: We have demonstrated that IBGMS, while not reaching statistical significance, may be associated with slightly reduced A1C and cost due to visiting physicians. PMID:25926853

Cost-benefit analysis of internet therapeutic intervention on patients with diabetes.

PubMed

Deng, Lan; White, Adam S; Pawlowska, Monika; Pottinger, Betty; Aydin, Jessica; Chow, Nelson; Tildesley, Hugh D

2015-04-01

With the emergence of IBGMS for allowing for patients to communicate their self-monitored blood glucose (SMBG) readings with their health care providers, their impact on the management of diabetes is becoming well-supported with regards to clinical benefits. Their impact on healthcare costs, however, has yet to be investigated. This study aims to determine the cost-benefits of such interventions in comparison to routine care. To analyze the cost-benefit of an Internet Blood Glucose Monitoring Service (IBGMS) in comparison to routine diabetes care. 200 patients were surveyed to assess the cost associated with doctor appointments in the past 12 months. Annual number of visits to medical services for diabetes and costs of transportation, parking, and time taken off work for visits were surveyed. Self-reported frequency of SMBG and most recent A1C were also surveyed. We compared 100 patients who used the IBGMS with 100 patients who only used routine care. There is a trend of lowered total cost in the intervention group compared to the control group. The control group spent $210.89 per year on visits to physicians; the intervention group spent $131.26 (P = 0.128). Patients in control group visited their endocrinologist 1.76 times per year, those in intervention group visited their endocrinologist 1.36 times per year, significantly less frequently than the control group (P = 0.014). Number of visits to other medical services is similar between the groups. Average A1C in intervention group is 7.57%, in control group is 7.69% (P = 0.309). We have demonstrated that IBGMS, while not reaching statistical significance, may be associated with slightly reduced A1C and cost due to visiting physicians.

"Difficult" Colorectal Polyps - Therapeutic Approach.

PubMed

Alecu, M; Simion, L; Ionescu, S; Brătucu, E; Straja, N D

2015-01-01

Endoscopic polypectomy is the gold standard in the treatment of colorectal polyps. The importance of polypectomy rests primarily on the fact that polyp-type lesions present a high risk of malignant degeneration, colorectal polyps being able, if left unattended therapeutically, to generate a colorectal cancer (CRC) - a lesion with a far more negative prognosis. Although preferable, endoscopic polypectomy of colorectal polyps is not always possible, multiple factors generating difficulties in performing this therapeutic measure. We performed a retrospective study in the First Surgical Clinic of the "Prof. Dr. Alexandu Trestioreanu" Bucharest Oncology Institute, spanning a period of 3 years (2008-2011), in which time 224 patients were diagnosed by colonoscopy with colorectal polyps, of whom 222 patients benefited from endoscopic polypectomy. The aim of the study was to identify "difficult" polyps and to identify the criteria for endoscopic surgery versus classic surgery as a therapeutic indication. Presence of "difficult" polyps was observed in 37.56% of the patients diagnosed with colorectal polyps. In over 88% of cases endoscopic polypectomy was possible, and for the remaining patients classic surgery was the therapeutic solution opted for. Presence of "difficult" polyps generates inconveniences in performing endoscopic polypectomy, increasing the risk of postoperative complication occurrence, as well as the duration of the operation. If the criteria for characterizing polyps as "difficult" are relatively well-established, the choice between endoscopic and classic surgery as a therapeutic measure is left at the free will of the operating surgeon, with the exception of situations in which classic surgery is resorted to for oncological reasons. Celsius.

Achieving the Promise of Therapeutic Extracellular Vesicles: The Devil is in Details of Therapeutic Loading.

PubMed

Sutaria, Dhruvitkumar S; Badawi, Mohamed; Phelps, Mitch A; Schmittgen, Thomas D

2017-05-01

Extracellular vesicles (EVs) represent a class of cell secreted organelles which naturally contain biomolecular cargo such as miRNA, mRNA and proteins. EVs mediate intercellular communication, enabling the transfer of functional nucleic acids from the cell of origin to the recipient cells. In addition, EVs make an attractive delivery vehicle for therapeutics owing to their increased stability in circulation, biocompatibility, low immunogenicity and toxicity profiles. EVs can also be engineered to display targeting moieties on their surfaces which enables targeting to desired tissues, organs or cells. While much has been learned on the role of EVs as cell communicators, the field of therapeutic EV application is currently under development. Critical to the future success of EV delivery system is the description of methods by which therapeutics can be successfully and efficiently loaded within the EVs. Two methods of loading of EVs with therapeutic cargo exist, endogenous and exogenous loading. We have therefore focused this review on describing the various published approaches for loading EVs with therapeutics.

Words matter: distinguishing "personalized medicine" and "biologically personalized therapeutics".

PubMed

Cherny, Nathan I; de Vries, Elisabeth G E; Emanuel, Linda; Fallowfield, Lesley; Francis, Prudence A; Gabizon, Alberto; Piccart, Martine J; Sidransky, David; Soussan-Gutman, Lior; Tziraki, Chariklia

2014-12-01

"Personalized medicine" has become a generic term referring to techniques that evaluate either the host or the disease to enhance the likelihood of beneficial patient outcomes from treatment interventions. There is, however, much more to personalization of care than just identifying the biotherapeutic strategy with the highest likelihood of benefit. In its new meaning, "personalized medicine" could overshadow the individually tailored, whole-person care that is at the bedrock of what people need and want when they are ill. Since names and definitional terms set the scope of the discourse, they have the power to define what personalized medicine includes or does not include, thus influencing the scope of the professional purview regarding the delivery of personalized care. Taxonomic accuracy is important in understanding the differences between therapeutic interventions that are distinguishable in their aims, indications, scope, benefits, and risks. In order to restore the due emphasis to the patient and his or her needs, we assert that it is necessary, albeit belated, to deconflate the contemporary term "personalized medicine" by taxonomizing this therapeutic strategy more accurately as "biologically personalized therapeutics" (BPT). The scope of truly personalized medicine and its relationship to biologically personalized therapeutics is described, emphasizing that the best of care must give due recognition and emphasis to both BPT and truly personalized medicine. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

[Therapeutic nursing: a systematic review].

PubMed

Lautenschläger, S; Müller, C; Immenschuh, U; Muser, J; Behrens, J

2014-08-01

For some years therapeutic service catalogues have been established in medical rehabilitation which have broadened our previous understanding of nursing actions. Currently, therapeutic nursing plays a prominent role in neurological early rehabilitation because the operations and procedures coding system (OPS) 8-552 within the DRG-System (Diagnosis Related Groups) states that therapeutic nursing must be carried out by specially trained nursing personnel. This requirement leads to inconsistencies in nursing practice and the medical service of the health insurance (MDK) since a definition of therapeutic nursing is lacking. A previous review of therapeutic nursing in 2003 focused primarily on the development of the therapeutic nursing role, but not on therapeutic nursing itself. The following article contains the first systematic review of the current state of research regarding a definition of therapeutic nursing. For this purpose, a systematic study was conducted to examine if there are, nationally or internationally, any definitions of therapeutic nursing and to identify what the therapeutic aspects of nursing are. The research included following database; Medline, Cinahl and Embase. Additionally, a research by hand of several German journals as well as textbooks and specialized literature was carried out. 5 studies were selected which define the term "therapeutic nursing". Among these are one review, one primary study, one theoretical discussion and one dissertation. Further twenty four studies were identified which do not define the term, but are closely related to the subject, and use or characterize the term in various contexts. The publications examined provided indications of duties, interventions and roles nurses should perform, but not how to carry these out, nor what is therapeutic about the nursing. At the same time, the low number of studies reveals that therapeutic nursing has barely been examined and demonstrates the lack of theoretically grounding

Non-additive benefit or cost? Disentangling the indirect effects that occur when plants bearing extrafloral nectaries and honeydew-producing insects share exotic ant mutualists.

PubMed

Savage, Amy M; Rudgers, Jennifer A

2013-06-01

In complex communities, organisms often form mutualisms with multiple different partners simultaneously. Non-additive effects may emerge among species linked by these positive interactions. Ants commonly participate in mutualisms with both honeydew-producing insects (HPI) and their extrafloral nectary (EFN)-bearing host plants. Consequently, HPI and EFN-bearing plants may experience non-additive benefits or costs when these groups co-occur. The outcomes of these interactions are likely to be influenced by variation in preferences among ants for honeydew vs. nectar. In this study, a test was made for non-additive effects on HPI and EFN-bearing plants resulting from sharing exotic ant guards. Preferences of the dominant exotic ant species for nectar vs. honeydew resources were also examined. Ant access, HPI and nectar availability were manipulated on the EFN-bearing shrub, Morinda citrifolia, and ant and HPI abundances, herbivory and plant growth were assessed. Ant-tending behaviours toward HPI across an experimental gradient of nectar availability were also tracked in order to investigate mechanisms underlying ant responses. The dominant ant species, Anoplolepis gracilipes, differed from less invasive ants in response to multiple mutualists, with reductions in plot-wide abundances when nectar was reduced, but no response to HPI reduction. Conversely, at sites where A. gracilipes was absent or rare, abundances of less invasive ants increased when nectar was reduced, but declined when HPI were reduced. Non-additive benefits were found at sites dominated by A. gracilipes, but only for M. citrifolia plants. Responses of HPI at these sites supported predictions of the non-additive cost model. Interestingly, the opposite non-additive patterns emerged at sites dominated by other ants. It was demonstrated that strong non-additive benefits and costs can both occur when a plant and herbivore share mutualist partners. These findings suggest that broadening the community

Non-additive benefit or cost? Disentangling the indirect effects that occur when plants bearing extrafloral nectaries and honeydew-producing insects share exotic ant mutualists

PubMed Central

Savage, Amy M.; Rudgers, Jennifer A.

2013-01-01

Background and Aims In complex communities, organisms often form mutualisms with multiple different partners simultaneously. Non-additive effects may emerge among species linked by these positive interactions. Ants commonly participate in mutualisms with both honeydew-producing insects (HPI) and their extrafloral nectary (EFN)-bearing host plants. Consequently, HPI and EFN-bearing plants may experience non-additive benefits or costs when these groups co-occur. The outcomes of these interactions are likely to be influenced by variation in preferences among ants for honeydew vs. nectar. In this study, a test was made for non-additive effects on HPI and EFN-bearing plants resulting from sharing exotic ant guards. Preferences of the dominant exotic ant species for nectar vs. honeydew resources were also examined. Methods Ant access, HPI and nectar availability were manipulated on the EFN-bearing shrub, Morinda citrifolia, and ant and HPI abundances, herbivory and plant growth were assessed. Ant-tending behaviours toward HPI across an experimental gradient of nectar availability were also tracked in order to investigate mechanisms underlying ant responses. Key Results The dominant ant species, Anoplolepis gracilipes, differed from less invasive ants in response to multiple mutualists, with reductions in plot-wide abundances when nectar was reduced, but no response to HPI reduction. Conversely, at sites where A. gracilipes was absent or rare, abundances of less invasive ants increased when nectar was reduced, but declined when HPI were reduced. Non-additive benefits were found at sites dominated by A. gracilipes, but only for M. citrifolia plants. Responses of HPI at these sites supported predictions of the non-additive cost model. Interestingly, the opposite non-additive patterns emerged at sites dominated by other ants. Conclusions It was demonstrated that strong non-additive benefits and costs can both occur when a plant and herbivore share mutualist partners. These

Emerging therapeutic delivery capabilities and challenges utilizing enzyme/protein packaged bacterial vesicles.

PubMed

Alves, Nathan J; Turner, Kendrick B; Medintz, Igor L; Walper, Scott A

2015-07-01

Nanoparticle-based therapeutics are poised to play a critical role in treating disease. These complex multifunctional drug delivery vehicles provide for the passive and active targeted delivery of numerous small molecule, peptide and protein-derived pharmaceuticals. This article will first discuss some of the current state of the art nanoparticle classes (dendrimers, lipid-based, polymeric and inorganic), highlighting benefits/drawbacks associated with their implementation. We will then discuss an emerging class of nanoparticle therapeutics, bacterial outer membrane vesicles, that can provide many of the nanoparticle benefits while simplifying assembly. Through molecular biology techniques; outer membrane vesicle hijacking potentially allows for stringent control over nanoparticle production allowing for targeted protein packaged nanoparticles to be fully synthesized by bacteria.

[Secondary benefits of cognitive rehabilitation for a chronic ethylic patient: effects on disorder consciousness, motivation, and global therapeutic cooperation].

PubMed

Siccardi, L; Vautel-Pons, D; dos Santos, M Teixera; Camus, N; Louchart de la Chapelle, S

2014-06-01

Alcoholism causes psychological, behavioral and cognitive symptoms that need to be addressed together. The neuropsychological alterations among alcohol-dependent people are considered to make the therapeutic work complex and longer. A cognitive rehabilitation program is sometimes difficult to achieve with these patients. Functional results are often difficult to anticipate. However, the consequences of this therapeutic approach are multiple and there are many interactions between psycho-affective, behavioral and cognitive components. A neuropsychological approach can be used like a tool to improve metacognition. A bad contribution to treatment programs is often secondary to the illusion of a satisfying intellectual functioning. Patients' motivation for the therapeutic work is very changeable. A complete consciousness of impairments can help them to stay involved. The following case shows the cognitive effects and secondary benefits associated with a neuropsychological work, which was carried out by a chronic ethylic patient with severe physical and cognitive symptoms. The patient aged 50, with a good qualification level (scientific section in the final year of secondary school, with no diploma, then attended a training program to become a croupier) was suffering from chronic alcoholism since his adolescence. He arrived in the closed unit after many hospitalizations in psychiatric and hepato-gastroenterology units. He had been showing mental confusion. He presented a frontal and subcortical profile of alcohol-related dementia according to Oslin's criteria. MRI revealed global cerebral atrophy, more pronounced on the fronto-parietal cortex with cerebellar leukoencephalopathy, but no pontine central myelinolysis. The neurocognitive program had two main lines: reducing attentional, executive and graphical deficits with training exercises (individual and group sessions) and compensating memory, and executive disorders with an external aid. The cognitive program had been

Employing the therapeutic operating characteristic (TOC) graph for individualised dose prescription

PubMed Central

2013-01-01

Background In current practice, patients scheduled for radiotherapy are treated according to ‘rigid’ protocols with predefined dose prescriptions that do not consider risk-taking preferences of individuals. The therapeutic operating characteristic (TOC) graph is applied as a decision-aid to assess the trade-off between treatment benefit and morbidity to facilitate dose prescription customisation. Methods Historical dose-response data from prostate cancer patient cohorts treated with 3D-conformal radiotherapy is used to construct TOC graphs. Next, intensity-modulated (IMRT) plans are generated by optimisation based on dosimetric criteria and dose-response relationships. TOC graphs are constructed for dose-scaling of the optimised IMRT plan and individualised dose prescription. The area under the TOC curve (AUC) is estimated to measure the therapeutic power of these plans. Results On a continuous scale, the TOC graph directly visualises treatment benefit and morbidity risk of physicians’ or patients’ choices for dose (de-)escalation. The trade-off between these probabilities facilitates the selection of an individualised dose prescription. TOC graphs show broader therapeutic window and higher AUCs with increasing target dose heterogeneity. Conclusions The TOC graph gives patients and physicians access to a decision-aid and read-out of the trade-off between treatment benefit and morbidity risks for individualised dose prescription customisation over a continuous range of dose levels. PMID:23497640

Risk evaluation and monitoring in multiple sclerosis therapeutics.

PubMed

Clanet, Michel C; Wolinsky, Jerry S; Ashton, Raymond J; Hartung, Hans-Peter; Reingold, Stephen C

2014-09-01

Risk for multiple sclerosis (MS) disease-modifying therapies (DMT) must be assessed on an ongoing basis. Early concerns regarding the first-approved DMTs for MS have been mitigated, but recently licensed therapies have been linked to possibly greater risks. The objective of this review is to discuss risk assessment in MS therapeutics based on an international workshop and comprehensive literature search and recommend strategies for risk assessment/monitoring. Assessment and perception of therapeutic risks vary between patients, doctors and regulators. Acceptability of risk depends on the magnitude of risk and the demonstrated clinical benefits of any agent. Safety signals must be distinguishable from chance occurrences in a clinical trial and in long-term use of medications. Post-marketing research is crucial for assessing longer-term safety in large patient cohorts. Reporting of adverse events is becoming more proactive, allowing more rapid identification of risks. Communication about therapeutic risks and their relationship to clinical benefit must involve patients in shared decision making. It is difficult to produce a general risk-assessment algorithm for all MS therapies. Specific algorithms are required for each DMT in every treated-patient population. New and evolving risks must be evaluated and communicated rapidly to allow patients and physicians to be well informed and able to share treatment decisions. © The Author(s) 2013.

Additional lesions detected in therapeutic scans with 177Lu-DOTATATE reflect higher affinity of 177Lu-DOTATATE for somatostatin receptors.

PubMed

Mirzaei, Siroos; Bastati, Brigitte; Lipp, Rainer W; Knoll, Peter; Zojer, Niklas; Ludwig, Heinz

2011-01-01

Peptide receptor-targeted radionuclide therapy (PRRT) of somatostatin receptor (SR)-expressing neuroendocrine tumors (NETs) has become an established therapeutic option in patients with advanced NETs. The aim of this study was to compare the lesion detection rate of (99m)Tc-EDDA/HYNIC-TOC, a newly developed tracer for NET imaging, with (177)Lu-DOTATATE used for PRRT. 8 patients (4 women, 4 men, age range 46-76 years) with histologically proven NETs, who showed high SR loads by (99m)Tc-EDDA/HYNIC-TOC scintigraphy, were treated with (177)Lu-DOTATATE. After treatment, all patients were subjected to whole-body scintigraphy with additional low-dose single-photon emission computed tomography (SPECT-CT) of the chest and abdomen. All patients demonstrated (177)Lu-DOTATATE accumulation in all lesions previously detected by (99m)Tc- EDDA/HYNIC-TOC scintigraphy. Three patients showed additional lesions in the liver and lungs. SPECT-CT after (177)Lu-DOTATATE therapy may be helpful in detecting additional lesions not seen using (99m)Tc-EDDA/HYNIC-TOC. This could reflect the broader affinity of (177)Lu-DOTATATE for SRs compared with (99m)Tc-EDDA/HYNIC-TOC. Copyright © 2011 S. Karger AG, Basel.

Neuroendocrine Associations Underlying the Persistent Therapeutic Effects of Classic Serotonergic Psychedelics

PubMed Central

Schindler, Emmanuelle A. D.; Wallace, Ryan M.; Sloshower, Jordan A.; D’Souza, Deepak C.

2018-01-01

Recent reports on the effects of psychedelic-assisted therapies for mood disorders and addiction, as well as the effects of psychedelics in the treatment of cluster headache, have demonstrated promising therapeutic results. In addition, the beneficial effects appear to persist well after limited exposure to the drugs, making them particularly appealing as treatments for chronic neuropsychiatric and headache disorders. Understanding the basis of the long-lasting effects, however, will be critical for the continued use and development of this drug class. Several mechanisms, including biological and psychological ones, have been suggested to explain the long-lasting effects of psychedelics. Actions on the neuroendocrine system are some such mechanisms that warrant further investigation in the study of persisting psychedelic effects. In this report, we review certain structural and functional neuroendocrinological pathologies associated with neuropsychiatric disorders and cluster headache. We then review the effects that psychedelic drugs have on those systems and provide preliminary support for potential long-term effects. The circadian biology of cluster headache is of particular relevance in this area. We also discuss methodologic considerations for future investigations of neuroendocrine system involvement in the therapeutic benefits of psychedelic drugs. PMID:29545753

Neuroendocrine Associations Underlying the Persistent Therapeutic Effects of Classic Serotonergic Psychedelics.

PubMed

Schindler, Emmanuelle A D; Wallace, Ryan M; Sloshower, Jordan A; D'Souza, Deepak C

2018-01-01

Recent reports on the effects of psychedelic-assisted therapies for mood disorders and addiction, as well as the effects of psychedelics in the treatment of cluster headache, have demonstrated promising therapeutic results. In addition, the beneficial effects appear to persist well after limited exposure to the drugs, making them particularly appealing as treatments for chronic neuropsychiatric and headache disorders. Understanding the basis of the long-lasting effects, however, will be critical for the continued use and development of this drug class. Several mechanisms, including biological and psychological ones, have been suggested to explain the long-lasting effects of psychedelics. Actions on the neuroendocrine system are some such mechanisms that warrant further investigation in the study of persisting psychedelic effects. In this report, we review certain structural and functional neuroendocrinological pathologies associated with neuropsychiatric disorders and cluster headache. We then review the effects that psychedelic drugs have on those systems and provide preliminary support for potential long-term effects. The circadian biology of cluster headache is of particular relevance in this area. We also discuss methodologic considerations for future investigations of neuroendocrine system involvement in the therapeutic benefits of psychedelic drugs.

Novel therapeutic Strategies for Targeting Liver Cancer Stem Cells

PubMed Central

Oishi, Naoki; Wang, Xin Wei

2011-01-01

The cancer stem cell (CSC) hypothesis was first proposed over 40 years ago. Advances in CSC isolation were first achieved in hematological malignancies, with the first CSC demonstrated in acute myeloid leukemia. However, using similar strategies and technologies, and taking advantage of available surface markers, CSCs have been more recently demonstrated in a growing range of epithelial and other solid organ malignancies, suggesting that the majority of malignancies are dependent on such a compartment. Primary liver cancer consists predominantly of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). It is believed that hepatic progenitor cells (HPCs) could be the origin of some HCCs and ICCs. Furthermore, stem cell activators such as Wnt/β-catenin, TGF-β, Notch and Hedgehog signaling pathways also expedite tumorigenesis, and these pathways could serve as molecular targets to assist in designing cancer prevention strategies. Recent studies indicate that additional factors such as EpCAM, Lin28 or miR-181 may also contribute to HCC progression by targeting HCC CSCs. Various therapeutic drugs that directly modulate CSCs have been examined in vivo and in vitro. However, CSCs clearly have a complex pathogenesis, with a considerable crosstalk and redundancy in signaling pathways, and hence targeting single molecules or pathways may have a limited benefit for treatment. Many of the key signaling molecules are shared by both CSCs and normal stem cells, which add further challenges for designing molecularly targeted strategies specific to CSCs but sparing normal stem cells to avoid side effects. In addition to the direct control of CSCs, many other factors that are needed for the maintenance of CSCs, such as angiogenesis, vasculogenesis, invasion and migration, hypoxia, immune evasion, multiple drug resistance, and radioresistance, should be taken into consideration when designing therapeutic strategies for HCC. Here we provide a brief review of

Imaging enabled platforms for development of therapeutics

NASA Astrophysics Data System (ADS)

Celli, Jonathan; Rizvi, Imran; Blanden, Adam R.; Evans, Conor L.; Abu-Yousif, Adnan O.; Spring, Bryan Q.; Muzikansky, Alona; Pogue, Brian W.; Finkelstein, Dianne M.; Hasan, Tayyaba

2011-03-01

Advances in imaging and spectroscopic technologies have enabled the optimization of many therapeutic modalities in cancer and noncancer pathologies either by earlier disease detection or by allowing therapy monitoring. Amongst the therapeutic options benefiting from developments in imaging technologies, photodynamic therapy (PDT) is exceptional. PDT is a photochemistry-based therapeutic approach where a light-sensitive molecule (photosensitizer) is activated with light of appropriate energy (wavelength) to produce reactive molecular species such as free radicals and singlet oxygen. These molecular entities then react with biological targets such as DNA, membranes and other cellular components to impair their function and lead to eventual cell and tissue death. Development of PDT-based imaging also provides a platform for rapid screening of new therapeutics in novel in vitro models prior to expensive and labor-intensive animal studies. In this study we demonstrate how an imaging platform can be used for strategizing a novel combination treatment strategy for multifocal ovarian cancer. Using an in vitro 3D model for micrometastatic ovarian cancer in conjunction with quantitative imaging we examine dose and scheduling strategies for PDT in combination with carboplatin, a chemotherapeutic agent presently in clinical use for management of this deadly form of cancer.

A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS).

PubMed

Cherny, N I; Sullivan, R; Dafni, U; Kerst, J M; Sobrero, A; Zielinski, C; de Vries, E G E; Piccart, M J

2015-08-01

The value of any new therapeutic strategy or treatment is determined by the magnitude of its clinical benefit balanced against its cost. Evidence for clinical benefit from new treatment options is derived from clinical research, in particular phase III randomised trials, which generate unbiased data regarding the efficacy, benefit and safety of new therapeutic approaches. To date, there is no standard tool for grading the magnitude of clinical benefit of cancer therapies, which may range from trivial (median progression-free survival advantage of only a few weeks) to substantial (improved long-term survival). Indeed, in the absence of a standardised approach for grading the magnitude of clinical benefit, conclusions and recommendations derived from studies are often hotly disputed and very modest incremental advances have often been presented, discussed and promoted as major advances or 'breakthroughs'. Recognising the importance of presenting clear and unbiased statements regarding the magnitude of the clinical benefit from new therapeutic approaches derived from high-quality clinical trials, the European Society for Medical Oncology (ESMO) has developed a validated and reproducible tool to assess the magnitude of clinical benefit for cancer medicines, the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS). This tool uses a rational, structured and consistent approach to derive a relative ranking of the magnitude of clinically meaningful benefit that can be expected from a new anti-cancer treatment. The ESMO-MCBS is an important first step to the critical public policy issue of value in cancer care, helping to frame the appropriate use of limited public and personal resources to deliver cost-effective and affordable cancer care. The ESMO-MCBS will be a dynamic tool and its criteria will be revised on a regular basis. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For

ACHIEVING THE PROMISE OF THERAPEUTIC EXTRACELLULAR VESICLES: THE DEVIL IS IN DETAILS OF THERAPEUTIC LOADING

PubMed Central

Sutaria, Dhruvitkumar S.; Badawi, Mohamed; Phelps, Mitch A.; Schmittgen, Thomas D.

2017-01-01

Extracellular vesicles (EVs) represent a class of cell secreted organelles which naturally contain biomolecular cargo such as miRNA, mRNA and proteins. EVs mediate intercellular communication, enabling the transfer of functional nucleic acids from the cell of origin to the recipient cells. In addition, EVs make an attractive delivery vehicle for therapeutics owing to their increased stability in circulation, biocompatibility, low immunogenicity and toxicity profiles. EVs can also be engineered to display targeting moieties on their surfaces which enables targeting to desired tissues, organs or cells. While much has been learned on the role of EVs as cell communicators, the field of therapeutic EV application is currently under development. Critical to the future success of EV delivery system is the description of methods by which therapeutics can be successfully and efficiently loaded within the EVs. Two methods of loading of EVs with therapeutic cargo exist, endogenous and exogenous loading. We have therefore focused this review on describing the various published approaches for loading EVs with therapeutics. PMID:28315083

Therapeutic touch and post-Hurricane Hugo stress.

PubMed

Olson, M; Sneed, N; Bonadonna, R; Ratliff, J; Dias, J

1992-06-01

This repeated-session design sought to answer questions about the effectiveness of therapeutic touch in reduction of stress for 23 individuals following a natural disaster. In addition, methodological issues related to the average length of time for a therapeutic-touch treatment and a method of documenting the nonverbal interaction between subject and toucher were investigated. Findings indicate that stressed people report themselves to be less stressed following therapeutic touch (p = .05). Time of therapeutic-touch intervention varied significantly between the touchers, with a range of 6.8 to 20 minutes. Qualitative data examining the interaction of toucher and subject raised a number of questions that require further study.

20 CFR 901.72 - Additional rules.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 4 2012-04-01 2012-04-01 false Additional rules. 901.72 Section 901.72 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS GOVERNING THE PERFORMANCE OF... additional rules regarding the enrollment of actuaries. [76 FR 17776, Mar. 31, 2011] ...

20 CFR 901.72 - Additional rules.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 4 2014-04-01 2014-04-01 false Additional rules. 901.72 Section 901.72 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS GOVERNING THE PERFORMANCE OF... additional rules regarding the enrollment of actuaries. [76 FR 17776, Mar. 31, 2011] ...

20 CFR 901.72 - Additional rules.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 4 2013-04-01 2013-04-01 false Additional rules. 901.72 Section 901.72 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS GOVERNING THE PERFORMANCE OF... additional rules regarding the enrollment of actuaries. [76 FR 17776, Mar. 31, 2011] ...

Potential Therapeutics for Vascular Cognitive Impairment and Dementia.

PubMed

Sun, Miao-Kun

2017-10-16

As the human lifespan increases, the number of people affected by age-related dementia is growing at an epidemic pace. Vascular pathology dramatically affects cognitive profiles, resulting in dementia and cognitive impairment. While vascular dementia itself constitutes a medical challenge, hypoperfusion/vascular risk factors enhance amyloid toxicity and other memory-damaging factors and hasten Alzheimer's disease (AD) and other memory disorders' progression, as well as negatively affect treatment outcome. Few therapeutic options are, however, currently available to improve the prognosis of patients with vascular dementia and cognitive impairment, mixed AD dementia with vascular pathology, or other memory disorders. Emerging evidence, however, indicates that, like AD and other memory disorders, synaptic impairment underlies much of the memory impairment in the cognitive decline of vascular cognitive impairment and vascular dementia. Effective rescues of the memory functions might be achieved through synaptic and memory therapeutics, targeting distinct molecular signaling pathways that support the formation of new synapses and maintaining their connections. Potential therapeutic agents include: 1) memory therapeutic agents that rescue synaptic and memory functions after the brain insults; 2) anti-pathologic therapeutics and an effective management of vascular risk factors; and 3) preventative therapeutic agents that achieve memory therapy through functional enhancement. Their development and potential as clinically effective memory therapeutics for vascular cognitive impairment and dementia are discussed in this review. These therapeutic agents are also likely to benefit patients with AD and/or other types of memory disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Autologous c-Kit+ Mesenchymal Stem Cell Injections Provide Superior Therapeutic Benefit as Compared to c-Kit+ Cardiac-Derived Stem Cells in a Feline Model of Isoproterenol-Induced Cardiomyopathy.

PubMed

Taghavi, Sharven; Sharp, Thomas E; Duran, Jason M; Makarewich, Catherine A; Berretta, Remus M; Starosta, Tim; Kubo, Hajime; Barbe, Mary; Houser, Steven R

2015-10-01

Cardiac- (CSC) and mesenchymal-derived (MSC) CD117+ isolated stem cells improve cardiac function after injury. However, no study has compared the therapeutic benefit of these cells when used autologously. MSCs and CSCs were isolated on day 0. Cardiomyopathy was induced (day 28) by infusion of L-isoproterenol (1,100 ug/kg/hour) from Alzet minipumps for 10 days. Bromodeoxyuridine (BrdU) was infused via minipumps (50 mg/mL) to identify proliferative cells during the injury phase. Following injury (day 38), autologous CSC (n = 7) and MSC (n = 4) were delivered by intracoronary injection. These animals were compared to those receiving sham injections by echocardiography, invasive hemodynamics, and immunohistochemistry. Fractional shortening improved with CSC (26.9 ± 1.1% vs. 16.1 ± 0.2%, p = 0.01) and MSC (25.1 ± 0.2% vs. 12.1 ± 0.5%, p = 0.01) as compared to shams. MSC were superior to CSC in improving left ventricle end-diastolic (LVED) volume (37.7 ± 3.1% vs. 19.9 ± 9.4%, p = 0.03) and ejection fraction (27.7 ± 0.1% vs. 19.9 ± 0.4%, p = 0.02). LVED pressure was less in MSC (6.3 ± 1.3 mmHg) as compared to CSC (9.3 ± 0.7 mmHg) and sham (13.3 ± 0.7); p = 0.01. LV BrdU+ myocytes were higher in MSC (0.17 ± 0.03%) than CSC (0.09 ± 0.01%) and sham (0.06 ± 01%); p < 0.001. Both CD117+ isolated CSC and MSC therapy improve cardiac function and attenuate pathological remodeling. However, MSC appear to confer additional benefit. © 2015 Wiley Periodicals, Inc.

Phenformin enhances the therapeutic benefit of BRAFV600E inhibition in melanoma

PubMed Central

Yuan, Ping; Ito, Koichi; Perez-Lorenzo, Rolando; Del Guzzo, Christina; Lee, Jung Hyun; Shen, Che-Hung; Bosenberg, Marcus W.; McMahon, Martin; Cantley, Lewis C.; Zheng, Bin

2013-01-01

Biguanides, such as the diabetes therapeutics metformin and phenformin, have demonstrated antitumor activity both in vitro and in vivo. The energy-sensing AMP-activated protein kinase (AMPK) is known to be a major cellular target of biguanides. Based on our discovery of cross-talk between the AMPK and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) signaling pathways, we investigated the antitumor effects of combining phenformin with a BRAF inhibitor PLX4720 on the proliferation of BRAF-mutated melanoma cells in vitro and on BRAF-driven tumor growth in vivo. Cotreatment of BRAF-mutated melanoma cell lines with phenformin and PLX4720 resulted in synergistic inhibition of cell viability, compared with the effects of the single agent alone. Moreover, treatment with phenformin significantly delayed the development of resistance to PLX4720 in cultured melanoma cells. Biochemical analyses showed that phenformin and PLX4720 exerted cooperative effects on inhibiting mTOR signaling and inducing apoptosis. Noticeably, phenformin selectively targeted subpopulations of cells expressing JARID1B, a marker for slow cycling melanoma cells, whereas PLX4720 selectively targeted JARID1B-negative cells. Finally, in contrast to their use as single agents, the combination of phenformin and PLX4720 induced tumor regression in both nude mice bearing melanoma xenografts and in a genetically engineered BRAFV600E/PTENnull-driven mouse model of melanoma. These results strongly suggest that significant therapeutic advantage may be achieved by combining AMPK activators such as phenformin with BRAF inhbitors for the treatment of melanoma. PMID:24145418

Intranasal delivery: physicochemical and therapeutic aspects.

PubMed

Costantino, Henry R; Illum, Lisbeth; Brandt, Gordon; Johnson, Paul H; Quay, Steven C

2007-06-07

Interest in intranasal (IN) administration as a non-invasive route for drug delivery continues to grow rapidly. The nasal mucosa offers numerous benefits as a target issue for drug delivery, such as a large surface area for delivery, rapid drug onset, potential for central nervous system delivery, and no first-pass metabolism. A wide variety of therapeutic compounds can be delivered IN, including relatively large molecules such as peptides and proteins, particularly in the presence of permeation enhancers. The current review provides an in-depth discussion of therapeutic aspects of IN delivery including consideration of the intended indication, regimen, and patient population, as well as physicochemical properties of the drug itself. Case examples are provided to illustrate the utility of IN dosing. It is anticipated that the present review will prove useful for formulation scientists considering IN delivery as a delivery route.

20 CFR 901.72 - Additional rules.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Additional rules. 901.72 Section 901.72 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS GOVERNING THE PERFORMANCE OF... additional rules regarding the enrollment of actuaries. Effective Date Note: At 76 FR 17776, Mar. 31, 2011...

Therapeutic relevance of ozone therapy in degenerative diseases: Focus on diabetes and spinal pain.

PubMed

Braidy, Nady; Izadi, Morteza; Sureda, Antoni; Jonaidi-Jafari, Nematollah; Banki, Abdolali; Nabavi, Seyed F; Nabavi, Seyed M

2018-04-01

Ozone, one of the most important air pollutants, is a triatomic molecule containing three atoms of oxygen that results in an unstable form due to its mesomeric structure. It has been well-known that ozone has potent ability to oxidize organic compounds and can induce respiratory irritation. Although ozone has deleterious effects, many therapeutic effects have also been suggested. Since last few decades, the therapeutic potential of ozone has gained much attention through its strong capacity to induce controlled and moderated oxidative stress when administered in precise therapeutic doses. A plethora of scientific evidence showed that the activation of hypoxia inducible factor-1α (HIF-1a), nuclear factor of activated T-cells (NFAT), nuclear factor-erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE), and activated protein-1 (AP-1) pathways are the main molecular mechanisms underlying the therapeutic effects of ozone therapy. Activation of these molecular pathways leads to up-regulation of endogenous antioxidant systems, activation of immune functions as well as suppression of inflammatory processes, which is important for correcting oxidative stress in diabetes and spinal pain. The present study intended to review critically the available scientific evidence concerning the beneficial properties of ozone therapy for treatment of diabetic complications and spinal pain. It finds benefit for integrating the therapy with ozone into pharmacological procedures, instead of a substitutive or additional option to therapy. © 2017 Wiley Periodicals, Inc.

Therapeutic Targeting of Siglecs using Antibody- and Glycan-based Approaches

PubMed Central

Angata, Takashi; Nycholat, Corwin M.; Macauley, Matthew S.

2015-01-01

The sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of immunomodulatory receptors whose functions are regulated by their glycan ligands. Siglecs are attractive therapeutic targets because of their cell-type specific expression pattern, endocytic properties, high expression on certain lymphomas/leukemias, and ability to modulate receptor signaling. Siglec-targeting approaches with therapeutic potential encompass antibody- and glycan-based strategies. Several antibody-based therapies are in clinical trials and continue to be developed for the treatment of lymphoma/leukemia and autoimmune disease, while the therapeutic potential of glycan-based strategies for cargo-delivery and immunomodulation is a promising new approach. Here, we review these strategies with special emphasis on emerging approaches and disease areas that may benefit from targeting the Siglec family. PMID:26435210

Therapeutic lighting design for the elderly: a review.

PubMed

Shikder, Shariful; Mourshed, Monjur; Price, Andrew

2012-11-01

Research suggests that specialised lighting design is essential to cater for the elderly users of a building because of reduced visual performance with increased age. This review aims to document what is known of the physical and psychological aspects of lighting and their role in promoting a healthy and safe environment for the elderly. A methodical review was carried out of published literature on the physical and psychological impacts of light on the elderly. Design standards and guides from professional organizations were evaluated to identify synergies and gaps between the evidence base and current practice. Lighting has been identified as a significant environmental attribute responsible for promoting physical and mental health of the elderly. The evidence related to visual performance was found to be robust. However, guides and standards appeared to have focused mostly on illumination requirements for specific tasks and have lacked detailed guidelines on vertical lighting and luminance design. This review has identified a growing body of evidence on the therapeutic benefits of lighting and its use in treating psychological disorders among the elderly. The experiments using light as a therapy have improved our understanding of the underlying principles, but the integration of therapeutic aspects of lighting in design practice and guidelines is lacking. While design guidelines discuss the physical needs of lighting for the elderly fairly well, they lack incorporation of photobiological impacts. Despite positive outcomes from research, the implementation of therapeutic aspects of lighting in buildings is still debatable due to insufficient relevant investigations and robustness of their findings. Collaborations between designers and physicians can contribute in delivering customised lighting solutions by considering disease types and needs. Further investigation needs to be carried out for translating therapeutic benefits to photometric units to implement them

Genetic determinants and potential therapeutic targets for pancreatic adenocarcinoma.

PubMed

Reznik, Robert; Hendifar, Andrew E; Tuli, Richard

2014-01-01

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in both men and women in the United States, carrying a 5-year survival rate of approximately 5%, which is the poorest prognosis of any solid tumor type. Given the dismal prognosis associated with PDAC, a more thorough understanding of risk factors and genetic predisposition has important implications not only for cancer prevention, but also for screening techniques and the development of personalized therapies. While screening of the general population is not recommended or practicable with current diagnostic methods, studies are ongoing to evaluate its usefulness in people with at least 5- to 10-fold increased risk of PDAC. In order to help identify high-risk populations who would be most likely to benefit from early detection screening tests for pancreatic cancer, discovery of additional pancreatic cancer susceptibility genes is crucial. Thus, specific gene-based, gene-product, and marker-based testing for the early detection of pancreatic cancer are currently being developed, with the potential for these to be useful as potential therapeutic targets as well. The goal of this review is to provide an overview of the genetic basis for PDAC with a focus on germline and familial determinants. A discussion of potential therapeutic targets and future directions in screening and treatment is also provided.

Genetic determinants and potential therapeutic targets for pancreatic adenocarcinoma

PubMed Central

Reznik, Robert; Hendifar, Andrew E.; Tuli, Richard

2014-01-01

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in both men and women in the United States, carrying a 5-year survival rate of approximately 5%, which is the poorest prognosis of any solid tumor type. Given the dismal prognosis associated with PDAC, a more thorough understanding of risk factors and genetic predisposition has important implications not only for cancer prevention, but also for screening techniques and the development of personalized therapies. While screening of the general population is not recommended or practicable with current diagnostic methods, studies are ongoing to evaluate its usefulness in people with at least 5- to 10-fold increased risk of PDAC. In order to help identify high-risk populations who would be most likely to benefit from early detection screening tests for pancreatic cancer, discovery of additional pancreatic cancer susceptibility genes is crucial. Thus, specific gene-based, gene-product, and marker-based testing for the early detection of pancreatic cancer are currently being developed, with the potential for these to be useful as potential therapeutic targets as well. The goal of this review is to provide an overview of the genetic basis for PDAC with a focus on germline and familial determinants. A discussion of potential therapeutic targets and future directions in screening and treatment is also provided. PMID:24624093

Comparison of Drug Benefits Provided by Veterans Affairs Canada and the Canadian Forces Health Services Group.

PubMed

Chow, Matthew; Wicks, Charles J; Ma, Janice; Grenier, Sylvain

2017-05-23

Drug benefits are provided at public expense to all actively serving Canadian Armed Forces (CAF) personnel, with ongoing drug coverage offered by Veterans Affairs Canada (VAC) for selected conditions following termination of employment. Differences in drug coverage between these programs could introduce risks for treatment disruption. Work was undertaken to establish a process that would allow systematic comparison of the entire VAC and CAF formularies, and to identify and explain discordant listings in 14 therapeutic categories that pose risk of adverse outcomes with sudden treatment interruption. Lists of medications were created for each program, including regular benefit and restricted use drugs, using files obtained from the claims processor in January 2015. Products were coded using the Anatomic-Therapeutic-Chemical (ATC) system. Degree of alignment within therapeutic categories was assessed based on the percentage of fifth-level ATCs that were covered in common. Discordantly listed drugs in 14 categories of concern were reviewed to identify similarities in product characteristics. A total of 1124 medications were identified in 80 therapeutic categories. Coverage of medications was identical in 11 categories, and overall, almost three-quarters of identified drugs (73.4%, n = 825) were covered in common by both plans. Many discordant listings reflected known differences in the programs' operating procedures. A number of discrepancies were also identified in newer therapeutic categories. There is significant overlap in the medications covered by the CAF and VAC drug benefit programs. Application of the ATC coding system allowed for discrepancies to be readily identified across the entire formulary, and in specific therapeutic categories of concern. © 2017 Journal of Population Therapeutics and Clinical Pharmacology. All rights reserved.

Polymer therapeutics in surgery: the next frontier

PubMed Central

Conlan, R. Steven; Whitaker, Iain S.

2016-01-01

Abstract Polymer therapeutics is a successful branch of nanomedicine, which is now established in several facets of everyday practice. However, to our knowledge, no literature regarding the application of the underpinning principles, general safety, and potential of this versatile class to the perioperative patient has been published. This study provides an overview of polymer therapeutics applied to clinical surgery, including the evolution of this demand‐oriented scientific field, cutting‐edge concepts, its implications, and limitations, illustrated by products already in clinical use and promising ones in development. In particular, the effect of design of polymer therapeutics on biophysical and biochemical properties, the potential for targeted delivery, smart release, and safety are addressed. Emphasis is made on principles, giving examples in salient areas of demand in current surgical practice. Exposure of the practising surgeon to this versatile class is crucial to evaluate and maximise the benefits that this established field presents and to attract a new generation of clinician–scientists with the necessary knowledge mix to drive highly successful innovation. PMID:27588210

Social Work Practice in the Digital Age: Therapeutic E-Mail as a Direct Practice Methodology

ERIC Educational Resources Information Center

Mattison, Marian

2012-01-01

The author addresses the risks and benefits of incorporating therapeutic e-mail communication into clinical social work practice. Consumer demand for online clinical services is growing faster than the professional response. E-mail, when used as an adjunct to traditional meetings with clients, offers distinct advantages and risks. Benefits include…

Fenetylline: therapeutic use, misuse and/or abuse.

PubMed

Kristen, G; Schaefer, A; von Schlichtegroll, A

1986-06-01

Fenetylline (CAPTAGON) is included in a list of compounds to be considered by a World Health Organization (WHO) Expert Committee in April 1985 for possible international scheduling under the Convention on Psychotropic Substances, 1971. For over 23 years, this central stimulant has been used therapeutically in hyperkinetic children and other indications in place of amphetamines and other central stimulants with higher risk levels. In good correspondence with recent animal data fenetylline also shows significant qualitative and quantitative differences compared to amphetamine in man. It has few adverse side effects, a lower abuse potential and little actual abuse compared to amphetamine. Thus its benefit/risk assessment is substantially more favourable than that of other central stimulants. For proper therapeutic use of the substance, prescription status is or should be required by national authorities.

ROCK as a therapeutic target for ischemic stroke.

PubMed

Sladojevic, Nikola; Yu, Brian; Liao, James K

2017-12-01

Stroke is a major cause of disability and the fifth leading cause of death. Currently, the only approved acute medical treatment of ischemic stroke is tissue plasminogen activator (tPA), but its effectiveness is greatly predicated upon early administration of the drug. There is, therefore, an urgent need to find new therapeutic options for acute stroke. Areas covered: In this review, we summarize the role of Rho-associated coiled-coil containing kinase (ROCK) and its potential as a therapeutic target in stroke pathophysiology. ROCK is a major regulator of cell contractility, motility, and proliferation. Many of these ROCK-mediated processes in endothelial cells, vascular smooth muscle cells, pericytes, astrocytes, glia, neurons, leukocytes, and platelets are important in stroke pathophysiology, and the inhibition of such processes could improve stroke outcome. Expert commentary: ROCK is a potential therapeutic target for cardiovascular disease and ROCK inhibitors have already been approved for human use in Japan and China for the treatment of acute stroke. Further studies are needed to determine the role of ROCK isoforms in the pathophysiology of cerebral ischemia and whether there are further therapeutic benefits with selective ROCK inhibitors.

Next Generation Antibody Therapeutics Using Bispecific Antibody Technology.

PubMed

Igawa, Tomoyuki

2017-01-01

Nearly fifty monoclonal antibodies have been approved to date, and the market for monoclonal antibodies is expected to continue to grow. Since global competition in the field of antibody therapeutics is intense, we need to establish novel antibody engineering technologies to provide true benefit for patients, with differentiated product values. Bispecific antibodies are among the next generation of antibody therapeutics that can bind to two different target antigens by the two arms of immunoglobulin G (IgG) molecule, and are thus believed to be applicable to various therapeutic needs. Until recently, large scale manufacturing of human IgG bispecific antibody was impossible. We have established a technology, named asymmetric re-engineering technology (ART)-Ig, to enable large scale manufacturing of bispecific antibodies. Three examples of next generation antibody therapeutics using ART-Ig technology are described. Recent updates on bispecific antibodies against factor IXa and factor X for the treatment of hemophilia A, bispecific antibodies against a tumor specific antigen and T cell surface marker CD3 for cancer immunotherapy, and bispecific antibodies against two different epitopes of soluble antigen with pH-dependent binding property for the elimination of soluble antigen from plasma are also described.

Benefit-Risk Analysis for Decision-Making: An Approach.

PubMed

Raju, G K; Gurumurthi, K; Domike, R

2016-12-01

The analysis of benefit and risk is an important aspect of decision-making throughout the drug lifecycle. In this work, the use of a benefit-risk analysis approach to support decision-making was explored. The proposed approach builds on the qualitative US Food and Drug Administration (FDA) approach to include a more explicit analysis based on international standards and guidance that enables aggregation and comparison of benefit and risk on a common basis and a lifecycle focus. The approach is demonstrated on six decisions over the lifecycle (e.g., accelerated approval, withdrawal, and traditional approval) using two case studies: natalizumab for multiple sclerosis (MS) and bedaquiline for multidrug-resistant tuberculosis (MDR-TB). © 2016 American Society for Clinical Pharmacology and Therapeutics.

Therapeutic applications of resveratrol and its derivatives on periodontitis.

PubMed

Chin, Yu-Tang; Cheng, Guei-Yun; Shih, Ya-Jung; Lin, Chi-Yu; Lin, Shan-Jen; Lai, Hsuan-Yu; Whang-Peng, Jacqueline; Chiu, Hsien-Chung; Lee, Sheng-Yang; Fu, Earl; Tang, Heng-Yuan; Lin, Hung-Yun; Liu, Leroy F

2017-09-01

Periodontitis is an inflammatory disease of the supporting tissues of the teeth induced by periodontopathic bacteria that results in the progressive destruction of periodontal tissues. Treatment of periodontitis is painful and time-consuming. Recently, herbal medicines have been considered for use in treating inflammation-related diseases, including periodontitis. Resveratrol and its derivative 2,3,5,4'-tetrahydroxystilbene-2-O-β-glucoside (THSG), a polyphenol extracted from Polygonum multiflorum, have anti-inflammatory properties and other medical benefits. Here, we highlight the importance of resveratrol and its glycosylated derivative as possible complementary treatments for periodontitis and their potential for development as innovative therapeutic strategies. In addition, we present evidence and discuss the mechanisms of action of resveratrol and THSG on periodontitis, focusing on Porphyromonas gingivalis-induced inflammatory responses in human gingival fibroblasts and animal modeling of ligature-induced periodontitis. We also illuminate the signal transduction pathways and the cytokines involved. © 2017 New York Academy of Sciences.

Nanotechnology and regenerative therapeutics in plastic surgery: The next frontier

PubMed Central

Tan, Aaron; Chawla, Reema; Natasha, G; Mahdibeiraghdar, Sara; Jeyaraj, Rebecca; Rajadas, Jayakumar; Hamblin, Michael R.; Seifalian, Alexander M.

2015-01-01

Summary The rapid ascent of nanotechnology and regenerative therapeutics as applied to medicine and surgery has seen an exponential rise in the scale of research generated in this field. This is evidenced not only by the sheer volume of papers dedicated to nanotechnology but also in a large number of new journals dedicated to nanotechnology and regenerative therapeutics specifically to medicine and surgery. Aspects of nanotechnology that have already brought benefits to these areas include advanced drug delivery platforms, molecular imaging and materials engineering for surgical implants. Particular areas of interest include nerve regeneration, burns and wound care, artificial skin with nanoelectronic sensors and head and neck surgery. This study presents a review of nanotechnology and regenerative therapeutics, with focus on its applications and implications in plastic surgery. PMID:26422652

Recent Trends in Therapeutic Approaches for Diabetes Management: A Comprehensive Update.

PubMed

Tiwari, Pragya

2015-01-01

Diabetes highlights a growing epidemic imposing serious social economic crisis to the countries around the globe. Despite scientific breakthroughs, better healthcare facilities, and improved literacy rate, the disease continues to burden several sections, especially middle and low income countries. The present trends indicate the rise in premature death, posing a major threat to global development. Scientific and technological advances have witnessed the development of newer generation of drugs like sulphonylureas, biguanides, alpha glucosidase inhibitors, and thiazolidinediones with significant efficacy in reducing hyperglycemia. Recent approaches in drug discovery have contributed to the development of new class of therapeutics like Incretin mimetics, Amylin analogues, GIP analogs, Peroxisome proliferator activated receptors, and dipeptidyl peptidase-4 inhibitor as targets for potential drugs in diabetes treatment. Subsequently, the identification and clinical investigation of bioactive substances from plants have revolutionized the research on drug discovery and lead identification for diabetes management. With a focus on the emerging trends, the review article explores the current statistical prevalence of the disease, discussing the benefits and limitations of the commercially available drugs. Additionally, the critical areas in clinical diabetology are discussed, with respect to prospects of statins, nanotechnology, and stem cell technology as next generation therapeutics and why the herbal formulations are consistently popular choice for diabetes medication and management.

Recent Trends in Therapeutic Approaches for Diabetes Management: A Comprehensive Update

PubMed Central

Tiwari, Pragya

2015-01-01

Diabetes highlights a growing epidemic imposing serious social economic crisis to the countries around the globe. Despite scientific breakthroughs, better healthcare facilities, and improved literacy rate, the disease continues to burden several sections, especially middle and low income countries. The present trends indicate the rise in premature death, posing a major threat to global development. Scientific and technological advances have witnessed the development of newer generation of drugs like sulphonylureas, biguanides, alpha glucosidase inhibitors, and thiazolidinediones with significant efficacy in reducing hyperglycemia. Recent approaches in drug discovery have contributed to the development of new class of therapeutics like Incretin mimetics, Amylin analogues, GIP analogs, Peroxisome proliferator activated receptors, and dipeptidyl peptidase-4 inhibitor as targets for potential drugs in diabetes treatment. Subsequently, the identification and clinical investigation of bioactive substances from plants have revolutionized the research on drug discovery and lead identification for diabetes management. With a focus on the emerging trends, the review article explores the current statistical prevalence of the disease, discussing the benefits and limitations of the commercially available drugs. Additionally, the critical areas in clinical diabetology are discussed, with respect to prospects of statins, nanotechnology, and stem cell technology as next generation therapeutics and why the herbal formulations are consistently popular choice for diabetes medication and management. PMID:26273667

Therapeutic Drug Monitoring in Children and Adolescents Under Pharmacotherapy With Olanzapine in Daily Clinical Practice.

PubMed

Fekete, Stefanie; Wewetzer, Christoph; Mehler-Wex, Claudia; Holtkamp, Kristian; Burger, Rainer; Reichert, Susanne; Taurines, Regina; Romanos, Marcel; Gerlach, Manfred; Egberts, Karin

2017-06-01

The relationship between daily dose, serum concentrations, and clinical outcomes of olanzapine as well as the influencing factors thereof in children and adolescents treated for different psychiatric disorders were investigated in daily clinical practice. In addition, it was examined whether the current recommended therapeutic range (TR) for adult patients with psychotic disorders is valid for minors. The Competence Network for Therapeutic Drug Monitoring (www.tdm-kjp.com) routinely collects demographic and clinical outcome data as well as serum concentrations of children and adolescents treated with psychotropics. The therapeutic effect is documented using the Clinical Global Impression Scale subscale for Global Improvement. Adverse drug reactions (ADRs) are assessed using the Udvalg for Kliniske Undersogelser-Side Effect Rating Scale. One hundred fifteen patients (mean age = 15.9 years; range = 10.4-18.8 years; 40.9% male) were included. The majority (72.1%) was cotreated with other psychotropic drugs. A positive medium linear relationship (r = 0.619; P < 0.001) between olanzapine dose (mean = 11.64 mg/d) and serum concentration (mean = 35.65 ng/mL) was found with a marked interindividual variability of serum concentrations. Neither relationship between olanzapine serum concentration and treatment response (clinical benefit documented in 80%) nor ADRs (documented in 53.3%, in 7.5% judged as severe) was detected. Most of the patients with psychotic and eating disorders (68.8% and 71.8%, respectively) had an olanzapine serum concentration within the TR suggested for adults. There are several limitations of this study because of the naturalistic design, and our results should therefore be interpreted with caution. As most of the patients showed a clinical benefit under olanzapine concentrations within the TR for adults and only a minority had severe ADRs, it is reasonable to conclude a similar TR for children, adolescents, and adults.

Medicinal benefits of marine invertebrates: sources for discovering natural drug candidates.

PubMed

De Zoysa, Mahanama

2012-01-01

Marine invertebrates are one of the major groups of organisms, which could be diversified under the major taxonomic groups of Porifera, Cnidaria, Mollusca, Arthropoda, Echinodermata, and many other minor phyla. To date, range of medicinal benefits and a significant number of marine natural products (MNPs) have been discovered from marine invertebrates. Seafood diet from edible marine invertebrates such as mollusks and crustaceans has been linked with various medicinal benefits to improve human health. Among marine invertebrates, spongers from phylum Porifera is the most dominant group responsible for discovering large number of MNPs, which have been used as template to develop therapeutic drugs. MNPs isolated from invertebrates have shown wide range of therapeutic properties including antimicrobial, antioxidant, antihypertensive, anticoagulant, anticancer, anti-inflammatory, wound healing and immune modulator, and other medicinal effects. Therefore, marine invertebrates are rich sources of chemical diversity and health benefits for developing drug candidates, cosmetics, nutritional supplements, and molecular probes that can be supported to increase the healthy life span of human. Copyright © 2012 Elsevier Inc. All rights reserved.

[Pharmacoeconomy in acne--evaluation of benefit and economics].

PubMed

Radtke, Marc A; Schäfer, Ines; Augustin, Matthias

2010-03-01

Acne belongs to the most common skin diseases and has a prevalence in the adolescence of nearly 100% and in adults of about 4%. The quality of life indes is significantly reduced und has impact on daily activities and social life and physical and psychological well being as well. The socioeconomic relevance is based not only on its prevalence but on direct and indirect costs. For acne therapy the knowledge on therapeutic costs is of importance but the cost benefit ratio as well. Evidence of therapeutic costs in acne and economic benefit of the therapy. Systematic review of Cochrane data. Calculations reveal general costs of acne treatment in Germany over 400 Mill.Euro per year. For the treatment with topical retinoids, BPO and antibiotics as well as systemic drugs only a few studies on costeffectiveness are available. For topical treatments results are not conclusive and dependent on the different health systems. New topical combinations may have a better economic outcome, however, more studies are needed. With regard to systemic therapies of moderate to severe acne based on the international references the costbenefit ratio favours the treatment with oral isotretinoin on the longterm outcome. Superiority is based on the relationship of costs and clinical outcome and the increased quality of life as well (cost-benefit ratio). It has to be emphazised that only longterm observations over years will lead to a valid calculation of costs and benefit. FACIT: Taking the high social and quality of life impact into consideration an early, well targeted and effective therapy is prevailing. Initial higher cost are balanced by a high quality of outcome under experienced dermatological supervision. The patients benefit is ranked over the final costs because of its medical, social and ethical aspects. To sample more differentiated data on pharmacoeconomic aspects well designed new clinical studies are to be set up.

Preterm labour: an overview of current and emerging therapeutics.

PubMed

Schwarz, Matthias K; Page, Patrick

2003-08-01

Preterm labour is a major cause of perinatal mortality and morbidity. However, during the past 40 years of clinical studies and despite the use of multiple therapeutic agents, the rate of preterm birth has not drastically declined. In 1991, it was estimated that in the US approximately 116,000 women admitted with acute episodes of preterm labour were treated each year with ritodrine, which is the first drug approved by the US FDA and still remains the standard therapy for treating preterm labour. Ritodrine (Yutopar( trade mark )) stimulates the beta(2)-adrenergic receptor throughout the body, causing an inhibitory action in different tissues that, among other side effects, also leads to an attenuation of uterine contractility. More recently, a new therapeutic agent, atosiban (Tractocile( trade mark )), a peptidic oxytocin receptor antagonist, has been introduced to the market. However, the use of the various pharmacological agents to treat preterm labour remains restricted, due to lack of uterine selectivity, low efficacy and potentially serious side effects for the mother or the foetus. Therefore, there is an urgent need to develop drugs with myometrial selectivity that would allow long-lasting inhibition of labour and prolong pregnancy up to a stage when good foetal maturation raises the chances of survival. One of the major obstacles hampering the development of new therapeutic agents is the marked inter-species difference in terms of preterm labour physiology, which complicates the preclinical evaluation of new candidate molecules in animal models of disease. In this review, the authors will provide a comprehensive update of past, current and new approaches for the management of preterm labour, including beta(2)-adrenergic agonists, calcium channel blockers, oxytocin antagonists, prostaglandin antagonists and other potential therapeutics. For each of the therapies used today, the review will cover the mechanism of action, benefit and adverse effects, and

Addition of meloxicam to the treatment of bovine clinical mastitis results in a net economic benefit to the dairy farmer.

PubMed

van Soest, Felix J S; Abbeloos, Elke; McDougall, Scott; Hogeveen, Henk

2018-04-01

Recently, it has been shown that the addition of meloxicam to standard antimicrobial therapy for clinical mastitis (CM) improves the conception rate of dairy cows contracting CM in the first 120 d in milk. The objective of our study was to assess whether this improved reproduction through additional treatment with meloxicam would result in a positive net economic benefit for the farmer. We developed a stochastic bio-economic simulation model, in which a dairy cow with CM in the first 120 d in milk was simulated. Two scenarios were simulated in which CM cases were treated with meloxicam in conjunction with antimicrobial therapy or with antimicrobial therapy alone. The scenarios differed for conception rates (31% with meloxicam or 21% without meloxicam) and for the cost of CM treatment. Sensitivity analyses were undertaken for the biological and economic components of the model to assess the effects of a wide range of inputs on inferences about the cost effectiveness of meloxicam treatment. Model results showed an average net economic benefit of €42 per CM case per year in favor of the meloxicam scenario. Cows in the no-meloxicam treatment scenario had higher returns on milk production, lower costs upon calving, and reduced costs of treatment. However, these did not outweigh the savings associated with lower feed intake, reduced number of inseminations, and the reduced culling rate. The net economic benefit favoring meloxicam therapy was a consequence of the better reproductive performance in the meloxicam scenario in which cows had a shorter calving to conception interval (132 vs. 143 d), a shorter intercalving interval (405 vs. 416 d), and fewer inseminations per conception (2.9 vs. 3.7) compared with cows in the no-meloxicam treatment scenario. This resulted in a shorter lactation, hence a lower lactational milk production (8,441 vs. 8,517 kg per lactation) with lower feeding costs in the meloxicam group. A lower culling rate (12 vs. 25%) resulted in lower

Chyawanprash: A review of therapeutic benefits as in authoritative texts and documented clinical literature.

PubMed

Narayana, D B Anantha; Durg, Sharanbasappa; Manohar, P Ram; Mahapatra, Anita; Aramya, A R

2017-02-02

booster. Additional studies involving measurement of current biomarkers of immunity pre- and post-consumption of the product as well as benefits accruing with the use of CP as an adjuvant are suggested. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis

PubMed Central

Blakeley, Jaishri O.; Plotkin, Scott R.

2016-01-01

Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are tumor-suppressor syndromes. Each syndrome is an orphan disease; however, the tumors that arise within them represent the most common tumors of the nervous system worldwide. Systematic investigation of the pathways impacted by the loss of function of neurofibromin (encoded by NF1) and merlin (encoded by NF2) have led to therapeutic advances for patients with NF1 and NF2. In the syndrome of SWN, the genetic landscape is more complex, with 2 known causative genes (SMARCB1 and LZTR1) accounting for up to 50% of familial SWN patients. The understanding of the molecular underpinnings of these syndromes is developing rapidly and offers more therapeutic options for the patients. In addition, common sporadic cancers harbor somatic alterations in NF1 (ie, glioblastoma, breast cancer, melanoma), NF2 (ie, meningioma, mesothelioma) and SMARCB1 (ie, atypical teratoid/rhabdoid tumors) such that advances in management of syndromic tumors may benefit patients both with and without germline mutations. In this review, we discuss the clinical and genetic features of NF1, NF2 and SWN, the therapeutic advances for the tumors that arise within these syndromes and the interaction between these rare tumor syndromes and the common tumors that share these mutations. PMID:26851632

The redox biology network in cancer pathophysiology and therapeutics.

PubMed

Manda, Gina; Isvoranu, Gheorghita; Comanescu, Maria Victoria; Manea, Adrian; Debelec Butuner, Bilge; Korkmaz, Kemal Sami

2015-08-01

The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1) and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic), greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular heterogeneity and the

Seaweed Polysaccharides - New Therapeutic Insights Against the Inflammatory Response in Diabetic Nephropathy.

PubMed

Vaishnudevi, Durairaj; Viswanathan, Pragasam

2017-01-01

The higher risk of diabetic nephropathy (DN) leads to end stage renal diseases worldwide, which is associated with chronic inflammation. Currently, the available treatments are limited, lack of efficacy and safety. Therefore, we are in need of novel targets and advanced treatments to reduce the necessity for the renal replacement therapy and burden of this disease management. Object/Methods: In this review, we performed through an inflammatory mechanism that contribute to DN, will provide a key point to the finding off novel therapeutic agents. In addition, we discuss the current anti-inflammatory drugs, an alternative approach of seaweed polysaccharides and also exploring the future perspective of anti-inflammatory natural seaweed compounds. Currently, seaweeds are taking majority of attention from scientists for targeting the various diseases. This will become a more significant part of the pipeline and alternate medicines for anti-inflammatory and chronic diseases. The potential benefits of natural seaweed novel compounds in inhibiting inflammatory pathways would be useful for the prevention of diabetic nephropathy. Thus, this therapy manifests the clinical benefits of these compounds in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Activin in acute pancreatitis: Potential risk-stratifying marker and novel therapeutic target.

PubMed

Staudacher, Jonas J; Yazici, Cemal; Carroll, Timothy; Bauer, Jessica; Pang, Jingbo; Krett, Nancy; Xia, Yinglin; Wilson, Annette; Papachristou, Georgios; Dirmeier, Andrea; Kunst, Claudia; Whitcomb, David C; Fantuzzi, Giamila; Jung, Barbara

2017-10-06

Acute Pancreatitis is a substantial health care challenge with increasing incidence. Patients who develop severe disease have considerable mortality. Currently, no reliable predictive marker to identify patients at risk for severe disease exists. Treatment is limited to rehydration and supporting care suggesting an urgent need to develop novel approaches to improve standard care. Activin is a critical modulator of inflammatory responses, but has not been assessed in pancreatitis. Here, we demonstrate that serum activin is elevated and strongly correlates with disease severity in two established murine models of acute pancreatitis induced by either cerulein or IL-12 + IL-18. Furthermore, in mice, inhibition of activin conveys survival benefits in pancreatitis. In addition, serum activin levels were measured from a retrospective clinical cohort of pancreatitis patients and high activin levels in patients at admission are predictive of worse outcomes, indicated by longer overall hospital and intensive care unit stays. Taken together, activin is a novel candidate as a clinical marker to identify those acute pancreatitis patients with severe disease who would benefit from aggressive treatment and activin may be a therapeutic target in severe acute pancreatitis.

Status of risk-benefit analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Horn, A.J.; Wilson, R.

1976-12-01

The benefits and deficiencies of cost benefit analysis are reviewed. It is pointed out that, if decision making involving risks and benefits is to improve, more attention must be paid to the clear presentation of the assumptions, values, and results. Reports need to present concise summaries which convey the uncertainties and limitations of the analysis in addition to the matrix of costs, risks, and benefits. As the field of risk-benefit analysis advances the estimation of risks and benefits will become more precise and implicit valuations will be made more explicit. Corresponding improvements must also be made to enhance communications betweenmore » the risk-benefit analyst and the accountable decision maker.« less

Pharmacology and potential therapeutic applications of nitric oxide-releasing non-steroidal anti-inflammatory and related nitric oxide-donating drugs

PubMed Central

Keeble, J E; Moore, P K

2002-01-01

This review examines the biological significance, therapeutic potential and mechanism(s) of action of a range of nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAID) and related nitric oxide-releasing donating drugs (NODD). The slow release of nitric oxide (NO) from these compounds leads to subtle changes in the profile of pharmacological activity of the parent, non-steroidal anti-inflammatory drugs (NSAID). For example, compared with NSAID, NO-NSAID cause markedly diminished gastrointestinal toxicity and improved anti-inflammatory and anti-nociceptive efficacy. In addition, nitroparacetamol exhibits hepatoprotection as opposed to the hepatotoxic activity of paracetamol. The possibility that NO-NSAID or NODD may be of therapeutic benefit in a wide variety of disease states including pain and inflammation, thrombosis and restenosis, neurodegenerative diseases of the central nervous system, colitis, cancer, urinary incontinence, liver disease, impotence, bronchial asthma and osteoporosis is discussed. PMID:12237248

Advanced MRI assessment to predict benefit of anti-programmed cell death 1 protein immunotherapy response in patients with recurrent glioblastoma.

PubMed

Qin, Lei; Li, Xiang; Stroiney, Amanda; Qu, Jinrong; Helgager, Jeffrey; Reardon, David A; Young, Geoffrey S

2017-02-01

We describe the imaging findings encountered in GBM patients receiving immune checkpoint blockade and assess the potential of quantitative MRI biomarkers to differentiate patients who derive therapeutic benefit from those who do not. A retrospective analysis was performed on longitudinal MRIs obtained on recurrent GBM patients enrolled on clinical trials. Among 10 patients with analyzable data, bidirectional diameters were measured on contrast enhanced T1 (pGd-T1WI) and volumes of interest (VOI) representing measurable abnormality suggestive of tumor were selected on pGdT1WI (pGdT1 VOI), FLAIR-T2WI (FLAIR VOI), and ADC maps. Intermediate ADC (IADC) VOI represented voxels within the FLAIR VOI having ADC in the range of highly cellular tumor (0.7-1.1 × 10 -3  mm 2 /s) (IADC VOI). Therapeutic benefit was determined by tissue pathology and survival on trial. IADC VOI, pGdT1 VOI, FLAIR VOI, and RANO assessment results were correlated with patient benefit. Five patients were deemed to have received therapeutic benefit and the other five patients did not. The average time on trial for the benefit group was 194 days, as compared to 81 days for the no benefit group. IADC VOI correlated well with the presence or absence of clinical benefit in 10 patients. Furthermore, pGd VOI, FLAIR VOI, and RANO assessment correlated less well with response. MRI reveals an initial increase in volumes of abnormal tissue with contrast enhancement, edema, and intermediate ADC suggesting hypercellularity within the first 0-6 months of immunotherapy. Subsequent stabilization and improvement in IADC VOI appear to better predict ultimate therapeutic benefit from these agents than conventional imaging.

Impacts of generic competition and benefit management practices on spending for prescription drugs: evidence from Medicare's Part D benefit.

PubMed

Sheingold, Steven; Nguyen, Nguyen Xuan

2014-01-01

This study estimates the effects of generic competition, increased cost-sharing, and benefit practices on utilization and spending for prescription drugs. We examined changes in Medicare price and utilization from 2007 to 2009 of all drugs in 28 therapeutic classes. The classes accounted for 80% of Medicare Part D spending in 2009 and included the 6 protected classes and 6 classes with practically no generic competition. All variables were constructed to measure each drug relative to its class at a specific plan sponsor. We estimated that the shift toward generic utilization had cut in half the rate of increase in the price of a prescription during 2007-2009. Specifically, the results showed that (1) rapid generic penetration had significantly held down costs per prescription, (2) copayment and other benefit practices shifted utilization to generics and favored brands, and (3) price increases were generally greater in less competitive classes of drugs. In many ways, Part D was implemented at a fortuitous time; since 2006, there have been relatively few new blockbuster drugs introduced, and many existing high-volume drugs used by beneficiaries were in therapeutic classes with multiple brands and generic alternatives. Under these conditions, our paper showed that plan sponsors have been able to contain costs by encouraging use of generics or drugs offering greater value within therapeutic classes. It is less clear what will happen to future Part D costs if a number of new and effective drugs for beneficiaries enter the market with no real competitors.

Novel therapeutic approaches for pulmonary arterial hypertension: Unique molecular targets to site-specific drug delivery.

PubMed

Vaidya, Bhuvaneshwar; Gupta, Vivek

2015-08-10

Pulmonary arterial hypertension (PAH) is a cardiopulmonary disorder characterized by increased blood pressure in the small arterioles supplying blood to lungs for oxygenation. Advances in understanding of molecular and cellular biology techniques have led to the findings that PAH is indeed a cascade of diseases exploiting multi-faceted complex pathophysiology, with cellular proliferation and vascular remodeling being the key pathogenic events along with several cellular pathways involved. While current therapies for PAH do provide for amelioration of disease symptoms and acute survival benefits, their full therapeutic potential is hindered by patient incompliance and off-target side effects. To overcome the issues related with current therapy and to devise a more selective therapy, various novel pathways are being investigated for PAH treatment. In addition, inability to deliver anti-PAH drugs to the disease site i.e., distal pulmonary arterioles has been one of the major challenges in achieving improved patient outcomes and improved therapeutic efficacy. Several novel carriers have been explored to increase the selectivity of currently approved anti-PAH drugs and to act as suitable carriers for the delivery of investigational drugs. In the present review, we have discussed potential of various novel molecular pathways/targets including RhoA/Rho kinase, tyrosine kinase, endothelial progenitor cells, vasoactive intestinal peptide, and miRNA in PAH therapeutics. We have also discussed various techniques for site-specific drug delivery of anti-PAH therapeutics so as to improve the efficacy of approved and investigational drugs. This review will provide gainful insights into current advances in PAH therapeutics with an emphasis on site-specific drug payload delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparison of microCT and an inverse finite element approach for biomechanical analysis: Results in a MSC therapeutic system for fracture healing

PubMed Central

Weis, Jared A.; Granero-Moltó, Froilán; Myers, Timothy J.; Longobardi, Lara; Spagnoli, Anna; Miga, Michael I.

2013-01-01

An important concern in the study of fracture healing is the ability to assess mechanical integrity in response to candidate therapeutics in small-animal systems. In recent reports, it has been proposed that microCT image-derived densitometric parameters could be used as a surrogate for mechanical property assessment. Recently, we have proposed an inverse methodology that iteratively reconstructs the modulus of elasticity of the lumped soft callus/hard callus region by integrating both intrinsic mechanical property (from biomechanical testing) and geometrical information (from microCT) within an inverse finite element analysis (FEA) to define a callus quality measure. In this paper, data from a therapeutic system involving mesenchymal stem cells is analyzed within the context of comparing traditional microCT densitometric and mechanical property metrics. In addition, a novel multi-parameter regression microCT parameter is analyzed as well as our inverse FEA metric. The results demonstrate that the inverse FEA approach was the only metric to successfully detect both longitudinal and therapeutic responses. While the most promising microCT-based metrics were adequate at early healing states, they failed to track late-stage mechanical integrity. In addition, our analysis added insight to the role of MSCs by demonstrating accelerated healing and was the only metric to demonstrate therapeutic benefits at late-stage healing. In conclusion, the work presented here indicates that microCT densitometric parameters are an incomplete surrogate for mechanical integrity. Additionally, our inverse FEA approach is shown to be very sensitive and may provide a first-step towards normalizing the often challenging process of assessing mechanical integrity of healing fractures. PMID:22766379

[Analysis of Late AMNOG Benefit Assessments].

PubMed

Rieder, Veronika; Hammerschmidt, Thomas

2018-04-26

Since 2011, new drugs are assessed at the time of launch in Germany (AMNOG). Based on this early benefit assessment (EBA), drug prices are negotiated. At this time, the evidence base might be weak. A later benefit assessment (LBA) is not done on a regular basis except for selected drugs. Our objective was to analyze the impact of LBAs of drugs for the same indication. Analysis of all completed LBAs between 2011 and 2016. 228 benefit assessments have been performed since 2011. 26 drugs were assessed twice for the same indication. Oncology and diabetes were the most common therapeutic areas in LBA and more pronounced than in EBA. 15 LBAs were due to the EBAs having a time limitation because of insufficient evidence base partially based on conditional approval. Time between EBA and LBA was 2.6 years. All 15 drugs had added benefit in the EBA, 4 got a better, 5 a worse assessment in the LBA. Seven drugs without added benefit in the EBA were assessed at the request of the manufacturer because of new data after 1.7 years. Three drugs could show added benefit in the LBA. Finally, 4 orphan drugs were reassessed according to the AMNOG regulation after achieving annual sales of 50 million euros. One got a better, 2 got a worse benefit assessment. Average improvement of benefit was +1.5 on a scale between - 3 (worst negative benefit) and +9 (highest positive benefit). Average deterioration of added benefit was - 1.4. Negotiated prices were significantly correlated with the change in the benefit assessment. LBA on a broader evidence base did not result in a significantly changed outcome. A general LBA for all drugs does not appear to be necessary because of the limited effect on the benefit assessment and the price when considering cost and administrative burden of the AMNOG benefit assessment. The selective approach of LBA for specific drugs is sufficient in cases in which the evidence base was limited at launch. © Georg Thieme Verlag KG Stuttgart · New York.

Social work practice in the digital age: therapeutic e-mail as a direct practice methodology.

PubMed

Mattison, Marian

2012-07-01

The author addresses the risks and benefits of incorporating therapeutic e-mail communication into clinical social work practice. Consumer demand for online clinical services is growing faster than the professional response. E-mail, when used as an adjunct to traditional meetings with clients, offers distinct advantages and risks. Benefits include the potential to reach clients in geographically remote and underserved communities, enhancing and extending the therapeutic relationship and improving treatment outcomes. Risks include threats to client confidentiality and privacy, liability coverage for practitioners, licensing jurisdiction, and the lack of competency standards for delivering e-mail interventions. Currently, the social work profession does not have adequate instructive guidelines and best-practice standards for using e-mail as a direct practice methodology. Practitioners need (formal) academic training in the techniques connected to e-mail exchanges with clients. The author describes the ethical and legal risks for practitioners using therapeutic e-mail with clients and identifies recommendations for establishing best-practice standards.

Therapeutic management of acute pulmonary embolism.

PubMed

Tromeur, Cécile; Van Der Pol, Liselotte M; Couturaud, Francis; Klok, Frederikus A; Huisman, Menno V

2017-08-01

Acute pulmonary embolism (PE) is a potentially fatal manifestation of venous thromboembolism. Prompt anticoagulant treatment is crucial for PE patients, which can decrease morbidity and mortality. Risk assessment is the cornerstone of the therapeutic management of PE. It guides physicians to the most appropriate treatment and selects patients for early discharge or home treatment. Areas covered: Here, we review the current treatments of acute PE according to contemporary risk stratification strategies, highlighting each step of PE therapeutic management. Expert commentary: Currently, direct oral anticoagulants (DOACs) represent the first-line therapy of patients presenting with non-high risk PE with a better risk-benefit ratios than vitamin K antagonists (VKAs) due to lower risk of major bleeding. Only high-risk patients with PE who present in shock should be treated with systematic thrombolysis, while surgical thrombectomy or catheter direct thrombolysis (CDT) should only be considered when thrombolysis is contraindicated because of too high bleeding risk.

Nanotechnology and regenerative therapeutics in plastic surgery: The next frontier.

PubMed

Tan, Aaron; Chawla, Reema; G, Natasha; Mahdibeiraghdar, Sara; Jeyaraj, Rebecca; Rajadas, Jayakumar; Hamblin, Michael R; Seifalian, Alexander M

2016-01-01

The rapid ascent of nanotechnology and regenerative therapeutics as applied to medicine and surgery has seen an exponential rise in the scale of research generated in this field. This is evidenced not only by the sheer volume of papers dedicated to nanotechnology but also in a large number of new journals dedicated to nanotechnology and regenerative therapeutics specifically to medicine and surgery. Aspects of nanotechnology that have already brought benefits to these areas include advanced drug delivery platforms, molecular imaging and materials engineering for surgical implants. Particular areas of interest include nerve regeneration, burns and wound care, artificial skin with nanoelectronic sensors and head and neck surgery. This study presents a review of nanotechnology and regenerative therapeutics, with focus on its applications and implications in plastic surgery. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. All rights reserved.

[Eye contact effects: A therapeutic issue?

PubMed

Baltazar, M; Conty, L

2016-12-01

The perception of a direct gaze - that is, of another individual's gaze directed at the observer that leads to eye contact - is known to influence a wide range of cognitive processes and behaviors. We stress that these effects mainly reflect positive impacts on human cognition and may thus be used as relevant tools for therapeutic purposes. In this review, we aim (1) to provide an exhaustive review of eye contact effects while discussing the limits of the dominant models used to explain these effects, (2) to illustrate the therapeutic potential of eye contact by targeting those pathologies that show both preserved gaze processing and deficits in one or several functions that are targeted by the eye contact effects, and (3) to propose concrete ways in which eye contact could be employed as a therapeutic tool. (1) We regroup the variety of eye contact effects into four categories, including memory effects, activation of prosocial behavior, positive appraisals of self and others and the enhancement of self-awareness. We emphasize that the models proposed to account for these effects have a poor predictive value and that further descriptions of these effects is needed. (2) We then emphasize that people with pathologies that affect memory, social behavior, and self and/or other appraisal, and self-awareness could benefit from eye contact effects. We focus on depression, autism and Alzheimer's disease to illustrate our proposal. To our knowledge, no anomaly of eye contact has been reported in depression. Patients suffering from Alzheimer disease, at the early and moderate stage, have been shown to maintain a normal amount of eye contact with their interlocutor. We take into account that autism is controversial regarding whether gaze processing is preserved or altered. In the first view, individuals are thought to elude or omit gazing at another's eyes while in the second, individuals are considered to not be able to process the gaze of others. We adopt the first stance

A Therapeutic Approach to Teaching Poetry: Individual Development, Psychology, and Social Reparation. Psychoanalysis, Education and Social Transformation

ERIC Educational Resources Information Center

Williams, Todd O.

2012-01-01

A Therapeutic Approach to Teaching Poetry develops a poetry pedagogy that offers significant benefits to students by helping them to achieve a sense of renewal (a deeper awareness of self and potentials) and reparation (a realistic, but positive and proactive worldview). Todd O. Williams offers a thorough examination of the therapeutic potential…

Heavy-ion lab to assess benefits and risk of radon therapy

NASA Astrophysics Data System (ADS)

Stafford, Ned

2012-04-01

Researchers in Germany, led by staff at the GSI heavy-ion centre in Darmstadt, have announced a three-and-a-half year project to study the potential risks of low-dose radon therapy as well as investigate its therapeutic benefits.

Therapeutic benefits of Tai Chi exercise: research review.

PubMed

Kuramoto, Alice M

2006-10-01

The majority of studies on Tai Chi conducted between 1996 and 2004 had focused on health and well being of Tai Chi exercise for senior adults. The results show that Tai Chi may lead to improved balance, reduced fear of falling, increased strength, increased functional mobility, greater flexibility, and increased psychological well-being, sleep enhancement for sleep disturbed elderly individuals, and increased cardio functioning. Wang, Collet, and Lau did a systematic review on Tai Chi research and found some limitations or biases existing in some of the studies, and it was difficult to draw firm conclusions about the benefits reported. Therefore, more well-designed studies are needed in the future. There need to be studies on the effects on younger and middle-aged people. More longitudinal studies are needed, since time is an important factor of physical and psychological interventions. Studies on the effects of Tai Chi on the immune system and bone loss reduction are still very exploratory and will be especially useful for arthritis patients and others with immune disorders. Future studies should investigate outcomes associated with Tai Chi training as a function of different instructional techniques, different Tai Chi styles, different diagnostic groups, and different age groups. It is not yet clear which of the components in Tai Chi makes the exercise form especially effective for seniors. Tai Chi exercise is a relatively "low tech" approach to preventing disability and maintaining physical performance in older adults. The positive effects of Tai Chi may be due solely to its relaxing, meditative aspects. The current data suggest that Tai Chi can influence older individuals' functioning and well being and provide some appreciation for why this exercise form has been practiced by older Chinese for more than 3 centuries.

Phenformin enhances the therapeutic benefit of BRAF(V600E) inhibition in melanoma.

PubMed

Yuan, Ping; Ito, Koichi; Perez-Lorenzo, Rolando; Del Guzzo, Christina; Lee, Jung Hyun; Shen, Che-Hung; Bosenberg, Marcus W; McMahon, Martin; Cantley, Lewis C; Zheng, Bin

2013-11-05

Biguanides, such as the diabetes therapeutics metformin and phenformin, have demonstrated antitumor activity both in vitro and in vivo. The energy-sensing AMP-activated protein kinase (AMPK) is known to be a major cellular target of biguanides. Based on our discovery of cross-talk between the AMPK and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) signaling pathways, we investigated the antitumor effects of combining phenformin with a BRAF inhibitor PLX4720 on the proliferation of BRAF-mutated melanoma cells in vitro and on BRAF-driven tumor growth in vivo. Cotreatment of BRAF-mutated melanoma cell lines with phenformin and PLX4720 resulted in synergistic inhibition of cell viability, compared with the effects of the single agent alone. Moreover, treatment with phenformin significantly delayed the development of resistance to PLX4720 in cultured melanoma cells. Biochemical analyses showed that phenformin and PLX4720 exerted cooperative effects on inhibiting mTOR signaling and inducing apoptosis. Noticeably, phenformin selectively targeted subpopulations of cells expressing JARID1B, a marker for slow cycling melanoma cells, whereas PLX4720 selectively targeted JARID1B-negative cells. Finally, in contrast to their use as single agents, the combination of phenformin and PLX4720 induced tumor regression in both nude mice bearing melanoma xenografts and in a genetically engineered BRAF(V600E)/PTEN(null)-driven mouse model of melanoma. These results strongly suggest that significant therapeutic advantage may be achieved by combining AMPK activators such as phenformin with BRAF inhbitors for the treatment of melanoma.

Instructional Basics: Oppelt Standard Method of Therapeutic and Recreational Ice Skating.

ERIC Educational Resources Information Center

Oppelt, Kurt

Detailed in the booklet is the standard ice skating method and considered are the benefits of therapeutic ice skating for the handicapped and aged. Values for the mentally retarded and physically handicapped are seen to include physiological (such as increased flexibility and improved posture), psychological (including satifaction and enhanced…

20 CFR 725.607 - Payments in addition to compensation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... time as, but in addition to, such benefits, unless review of the order making such award is sought as... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Payments in addition to compensation. 725.607 Section 725.607 Employees' Benefits EMPLOYMENT STANDARDS ADMINISTRATION, DEPARTMENT OF LABOR FEDERAL COAL...

The public library as therapeutic landscape: a qualitative case study.

PubMed

Brewster, Liz

2014-03-01

The idea of the therapeutic landscape has been widely used to describe the relationship between place and improvements in mental health. This paper uses data from a qualitative study conducted with people with mental health problems to outline the role of the public library as a therapeutic landscape. It situates the public library as a space that is simultaneously familiar and welcoming, comforting and calming, and empowering. Further, the paper reflects on the impact of proposed library closures in light of these previously hidden benefits, thinking about the library's role as an environment and not as a service provider. Copyright © 2014 Elsevier Ltd. All rights reserved.

The efficacy of therapeutic ultrasound for rotator cuff tendinopathy: A systematic review and meta-analysis.

PubMed

Desmeules, François; Boudreault, Jennifer; Roy, Jean-Sébastien; Dionne, Clermont; Frémont, Pierre; MacDermid, Joy C

2015-08-01

A systematic review and meta-analysis on the efficacy of therapeutic ultrasound (US) in adults suffering from rotator cuff tendinopathy. A literature search was conducted in four databases for randomized controlled trials (RCT) published until 12/2013, comparing the efficacy of US to any other interventions in adults suffering from rotator cuff tendinopathy. The Cochrane Risk of Bias tool was used to evaluate the risk of bias of included studies. Data were summarized qualitatively or quantitatively. Eleven RCTs with a low mean methodological score (50.0% ± 15.6%) were included. Therapeutic US did not provide greater benefits than a placebo intervention or advice in terms of pain reduction and functional improvement. When provided in conjunction with exercise, US therapy is not superior to exercise alone in terms of pain reduction and functional improvement (pooled mean difference of the Constant-Murley score: -0.26 with 95% confidence interval of -3.84 to 3.32). Laser therapy was found superior to therapeutic US in terms of pain reduction. Based on low to moderate level evidence, therapeutic US does not provide any benefit compared to a placebo or advice, to laser therapy or when combined to exercise. More methodologically sound studies on the efficacy of therapeutic US are warranted. Copyright © 2014 Elsevier Ltd. All rights reserved.

Therapeutic benefit of internet-based lifestyle counselling for hypertension.

PubMed

Nolan, Robert P; Liu, Sam; Shoemaker, J Kevin; Hachinski, Vladimir; Lynn, Hazel; Mikulis, David J; Wennberg, Richard A; Moy Lum-Kwong, Margaret; Zbib, Ahmad

2012-05-01

Preventive electronic (e)-counselling has been shown to reduce cardiovascular risk factors. However, heterogeneity in outcomes is commonly reported due to differences in e-protocols. We incorporated key features of an established behavioural therapy, motivational interviewing, to help standardize e-counselling in order to reduce blood pressure in patients with hypertension. Subjects (n = 387, mean age = 56 years, 59% female, 72% taking ≥ 1 antihypertensive drug) were diagnosed with stage 1 or 2 hypertension. Subjects were randomized to a 4-month protocol of e-counselling (beta version of the "Blood Pressure Action Plan", Heart and Stroke Foundation of Canada) vs waitlist control (general e-information on heart-healthy living). Outcomes were systolic, diastolic, and pulse pressures, and total lipoprotein cholesterol after treatment. Intention to treat analysis did not find a significant group difference in outcomes due to contamination across the 2 arms of this trial. However, per protocol analysis indicated that subjects receiving ≥ 8 e-counselling messages (a priori therapeutic dose) vs 0 e-counselling messages (control) demonstrated greater reduction in systolic blood pressure (mean, -8.9 mm Hg; 95% confidence interval [CI], -11.5 to -6.4 vs -5.0 mm Hg; 95% CI, -6.7 to -3.3, P = 0.03), pulse pressure (-6.1 mm Hg; 95% CI, -8.1 to -4.1 vs -3.1 mm Hg; 95% CI, -4.3 to -1.8, P = 0.02) and total cholesterol (-0.24 mmol/L; 95% CI, -0.43 to -0.06 vs 0.05 mmol/L; 95% CI, -0.06 to 0.16, P = 0.03), but not diastolic blood pressure. These findings support the merit of evaluating whether e-counselling can improve blood pressure control and reduce cardiovascular risk over the long-term. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

PubMed

Straube, Andreas; Aicher, Bernhard; Fiebich, Bernd L; Haag, Gunther

2011-03-31

Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.As an example the fixed-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

PubMed Central

2011-01-01

Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden the array of therapeutic

Remote monitoring of heart failure: benefits for therapeutic decision making.

PubMed

Martirosyan, Mihran; Caliskan, Kadir; Theuns, Dominic A M J; Szili-Torok, Tamas

2017-07-01

Chronic heart failure is a cardiovascular disorder with high prevalence and incidence worldwide. The course of heart failure is characterized by periods of stability and instability. Decompensation of heart failure is associated with frequent and prolonged hospitalizations and it worsens the prognosis for the disease and increases cardiovascular mortality among affected patients. It is therefore important to monitor these patients carefully to reveal changes in their condition. Remote monitoring has been designed to facilitate an early detection of adverse events and to minimize regular follow-up visits for heart failure patients. Several new devices have been developed and introduced to the daily practice of cardiology departments worldwide. Areas covered: Currently, special tools and techniques are available to perform remote monitoring. Concurrently there are a number of modern cardiac implantable electronic devices that incorporate a remote monitoring function. All the techniques that have a remote monitoring function are discussed in this paper in detail. All the major studies on this subject have been selected for review of the recent data on remote monitoring of HF patients and demonstrate the role of remote monitoring in the therapeutic decision making for heart failure patients. Expert commentary: Remote monitoring represents a novel intensified follow-up strategy of heart failure management. Overall, theoretically, remote monitoring may play a crucial role in the early detection of heart failure progression and may improve the outcome of patients.

Additive Manufacturing Infrared Inspection

NASA Technical Reports Server (NTRS)

Gaddy, Darrell; Nettles, Mindy

2015-01-01

The Additive Manufacturing Infrared Inspection Task started the development of a real-time dimensional inspection technique and digital quality record for the additive manufacturing process using infrared camera imaging and processing techniques. This project will benefit additive manufacturing by providing real-time inspection of internal geometry that is not currently possible and reduce the time and cost of additive manufactured parts with automated real-time dimensional inspections which deletes post-production inspections.

COGNITION AS A THERAPEUTIC TARGET IN LATE-LIFE DEPRESSION: POTENTIAL FOR NICOTINIC THERAPEUTICS

PubMed Central

Zurkovsky, Lilia; Taylor, Warren D.; Newhouse, Paul A.

2013-01-01

Depression is associated with impairments to cognition and brain function at any age, but such impairments in the elderly are particularly problematic because of the additional burden of normal cognitive aging and in some cases, structural brain pathology. Individuals with late-life depression exhibit impairments in cognition and brain structural integrity, alongside mood dysfunction. Antidepressant treatment improves symptoms in some but not all patients, and those who benefit may not return to the cognitive and functional level of nondepressed elderly. Thus, for comprehensive treatment of late-life depression, it may be necessary to address both the affective and cognitive deficits. In this review, we propose a model for the treatment of late-life depression in which nicotinic stimulation is used to improve cognitive performance and improve the efficacy of an antidepressant treatment of the syndrome of late-life depression. The cholinergic system is well-established as important to cognition. Although muscarinic stimulation may exacerbate depressive symptoms, nicotinic stimulation may improve cognition and neural functioning without a detriment to mood. While some studies of nicotinic subtype specific receptor agonists have shown promise in improving cognitive performance, less is known regarding how nicotinic receptor stimulation affects cognition in depressed elderly patients. Late-life depression thus represents a new therapeutic target for the development of nicotinic agonist drugs and parallel treatment of cognitive dysfunction along with medical and psychological approaches to treating mood dysfunction may be necessary to ensure full resolution of depressive illness in aging. PMID:23933385

Optimization of a therapeutic protocol for intravenous injection of human mesenchymal stem cells after cerebral ischemia in adult rats.

PubMed

Omori, Yoshinori; Honmou, Osamu; Harada, Kuniaki; Suzuki, Junpei; Houkin, Kiyohiro; Kocsis, Jeffery D

2008-10-21

The systemic injection of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has therapeutic benefits after cerebral artery occlusion in rats, and may have multiple therapeutic effects at various sites and times within the lesion as the cells respond to a particular pathological microenvironment. However, the comparative therapeutic benefits of multiple injections of hMSCs at different time points after cerebral artery occlusion in rats remain unclear. In this study, we induced middle cerebral artery occlusion (MCAO) in rats using intra-luminal vascular occlusion, and infused hMSCs intravenously at a single 6 h time point (low and high cell doses) and various multiple time points after MCAO. From MRI analyses lesion volume was reduced in all hMSC cell injection groups as compared to serum alone injections. However, the greatest therapeutic benefit was achieved following a single high cell dose injection at 6 h post-MCAO, rather than multiple lower cell infusions over multiple time points. Three-dimensional analysis of capillary vessels in the lesion indicated that the capillary volume was equally increased in all of the cell-injected groups. Thus, differences in functional outcome in the hMSC transplantation subgroups are not likely the result of differences in angiogenesis, but rather from differences in neuroprotective effects.

Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics

PubMed Central

Rath, Timo; Baker, Kristi; Dumont, Jennifer A.; Peters, Robert T.; Jiang, Haiyan; Qiao, Shuo-Wang; Lencer, Wayne I.; Pierce, Glenn F.; Blumberg, Richard S.

2016-01-01

Nearly 350 IgG-based therapeutics are approved for clinical use or are under development for many diseases lacking adequate treatment options. These include molecularly engineered biologicals comprising the IgG Fc-domain fused to various effector molecules (so-called Fc-fusion proteins) that confer the advantages of IgG, including binding to the neonatal Fc receptor (FcRn) to facilitate in vivo stability, and the therapeutic benefit of the specific effector functions. Advances in IgG structure-function relationships and an understanding of FcRn biology have provided therapeutic opportunities for previously unapproachable diseases. This article discusses approved Fc-fusion therapeutics, novel Fc-fusion proteins and FcRn-dependent delivery approaches in development, and how engineering of the FcRn–Fc interaction can generate longer-lasting and more effective therapeutics. PMID:24156398

20 CFR 226.12 - Employee vested dual benefit.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Employee vested dual benefit. 226.12 Section 226.12 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT... vested dual benefit. (a) General. An employee vested dual benefit is payable, in addition to tiers I and...

20 CFR 226.12 - Employee vested dual benefit.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Employee vested dual benefit. 226.12 Section 226.12 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT... vested dual benefit. (a) General. An employee vested dual benefit is payable, in addition to tiers I and...

20 CFR 226.12 - Employee vested dual benefit.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Employee vested dual benefit. 226.12 Section 226.12 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT... vested dual benefit. (a) General. An employee vested dual benefit is payable, in addition to tiers I and...

Therapeutic abortion: the psychiatric nurse as therapist, liaison, and consultant.

PubMed

Zahourek, R; Tower, M

1971-01-01

It is noted that as abortion becomes an accepted medical practice, more nurses will be involved in the treatment and counseling of the therapeutic abortion patient. The authors, psychiatric nurses in a Colorado comprehensive urban mental health center, became involved in the treatment of the therapeutic abortion patient with the passing of the State's liberalized 1967 abortion law. As they became involved with all aspects of therapeutic abortion patients' care, they identified 3 specific roles for the psychiatric nurse: 1) providing direct They treatment, 2) providing liaison service and promoting continuity of care for the patient, and 3) providing consultation service to the staff involved with the patient. As the psychiatric nurses shared their own mixed feelings about abortion with the obstetrical staff, the staff began to feel less guilty and less alone with their feelings. The became more involved with the patients and benefited them more.

Potential explanations for control group benefit.

PubMed

Nichols, Linda O; Martindale-Adams, Jennifer L; Burns, Robert; Graney, Marshall J; Zuber, Jeffrey K; Kennedy, Sarah E

2012-10-01

Estimating effectiveness of clinical interventions depends on detecting differences between the responses of intervention and control groups. The outcome, intervention, and moderating factors all may influence the between group change. The absence of a clinically or statistically meaningful difference may also result from control group improvement due to nonspecific factors such as participants' perception of attention, positive regard, expectations, desire to please, and therapeutic alliance with the care provider. We examined perceived benefit and sources of benefit for control caregivers who participated in the CONNECT randomized controlled trial of a dementia caregiving intervention. After the final scheduled data collection in CONNECT, control group participants were asked whether they believed they benefited from study participation. Those who reported benefit were asked to describe the benefit received. Data were analyzed qualitatively. Of 60 available control caregivers, 82% reported a perceived benefit from study participation in five areas: getting information about dementia and caregiving; having someone to talk to and feeling supported; receiving understanding and validation of feelings; knowledge that others were in similar situations; and perceived appreciation of own abilities. Control caregivers who reported benefit were less burdened and depressed and spent less time on duty at baseline than those who did not report benefit. From caregivers' responses, we have identified the assessment battery, both content and time spent in data collection, as a possible mechanism of action for benefit. Study limitations include the better baseline characteristics of the control caregivers who reported benefit, the sample size of benefit control caregivers, the possibility of perceptions of benefit being a function of social desirability, and the lack of a similar question about benefit being asked of intervention caregivers. These findings suggest that the

Clinically advancing and promising polymer-based therapeutics.

PubMed

Souery, Whitney N; Bishop, Corey J

2018-02-01

In this review article, we will examine the history of polymers and their evolution from provisional World War II materials to medical therapeutics. To provide a comprehensive look at the current state of polymer-based therapeutics, we will classify technologies according to targeted areas of interest, including central nervous system-based and intraocular-, gastrointestinal-, cardiovascular-, dermal-, reproductive-, skeletal-, and neoplastic-based systems. Within each of these areas, we will consider several examples of novel, clinically available polymer-based therapeutics; in addition, this review will also include a discussion of developing therapies, ranging from the in vivo to clinical trial stage, for each targeted area of treatment. Finally, we will emphasize areas of patient care in need of more effective, accessible, and targeted treatment approaches where polymer-based therapeutics may offer potential solutions. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Additional benefit of dietitian involvement in dialysis staffs-led diet education on uncontrolled hyperphosphatemia in hemodialysis patients.

PubMed

Tsai, Wan-Chuan; Yang, Ju-Yeh; Luan, Chia-Chin; Wang, Yuh-Jiun; Lai, Yu-Chuan; Liu, Lie-Chuan; Peng, Yu-Sen

2016-10-01

Sustained adherence to dietary phosphorus (P) restriction recommendations among hemodialysis patients is questionable. The aim of this study was to evaluate the effectiveness of additional diet education delivered by a dietitian on the control of hyperphosphatemia. We conducted an 8-month prospective observational study in hemodialysis patients who had uncontrolled hyperphosphatemia. In the first half of the study (experimental) period, the dialysis nurses and physicians provided the routine dietetic education with the control group (n = 31), while the experimental group (n = 30) received the routine dietetic education plus an additional diet education delivered by dietitians. Both groups received the routine dietetic education in the rest of the study period to test whether the improvement of serum P level was sustained. The primary outcomes were changes in serum P level. At baseline, there was no significant difference in serum P levels between groups (P = 0.27). In the experimental period, monthly serum P levels decreased significantly in both groups (P < 0.001) and the magnitudes of reduction were 1.81 ± 1.46 and 0.94 ± 1.33 mg/dL in the experimental and control groups, respectively (P = 0.02), at the end. The experimental group maintained such improvement for one more month (P = 0.02), but faded out over time. Renal diet education guided either by dietitians plus dialysis staffs or dialysis staffs alone reduces serum P level and dietitian-guided diet education provides an additional benefit on controlling hyperphosphatemia in hemodialysis patients.

Exploring Animal-Assisted Programs with Children in School and Therapeutic Contexts

ERIC Educational Resources Information Center

Friesen, Lori

2010-01-01

Animal-Assisted programs with children are becoming increasingly popular in school and therapeutic settings. This article provides an overview of the benefits accrued by children as well as the concerns with programs which involve animals, and therapy dogs in particular, in these environments. Research over the past 30 years indicates that therapy…

Therapeutic Plasma Exchange in Critically Ill Children Requiring Intensive Care.

PubMed

Cortina, Gerard; McRae, Rosemary; Chiletti, Roberto; Butt, Warwick

2018-02-01

To characterize the clinical indications, procedural safety, and outcome of critically ill children requiring therapeutic plasma exchange. Retrospective observational study based on a prospective registry. Tertiary and quaternary referral 30-bed PICU. Forty-eight critically ill children who received therapeutic plasma exchange during an 8-year period (2007-2014) were included in the study. Therapeutic plasma exchange. A total of 48 patients underwent 244 therapeutic plasma exchange sessions. Of those, therapeutic plasma exchange was performed as sole procedure in 193 (79%), in combination with continuous renal replacement therapy in 40 (16.4%) and additional extracorporeal membrane oxygenation in 11 (4.6%) sessions. The most common admission diagnoses were hematologic disorders (30%), solid organ transplantation (20%), neurologic disorders (20%), and rheumatologic disorders (15%). Complications associated with the procedure occurred in 50 (21.2%) therapeutic plasma exchange sessions. Overall, patient survival from ICU was 82%. Although patients requiring therapeutic plasma exchange alone (n = 31; 64%) had a survival rate of 97%, those with additional continuous renal replacement therapy (n = 13; 27%) and extracorporeal membrane oxygenation (n = 4; 8%) had survival rates of 69% and 50%, respectively. Factors associated with increased mortality were lower Pediatric Index of Mortality 2 score, need for mechanical ventilation, higher number of failed organs, and longer ICU stay. Our results indicate that, in specialized centers, therapeutic plasma exchange can be performed relatively safely in critically ill children, alone or in combination with continuous renal replacement therapy and extracorporeal membrane oxygenation. Outcome in children requiring therapeutic plasma exchange alone is excellent. However, survival decreases with the number of failed organs and the need for continuous renal replacement therapy and extracorporeal membrane oxygenation.

Data Safety Monitoring Boards and Other Study Methodologies that Address Subject Safety in "High-Risk" Therapeutic Trials in Youths

ERIC Educational Resources Information Center

Carandang, Carlo; Santor, Darcy; Gardner, David M.; Carrey, Normand; Kutcher, Stan

2007-01-01

The underlying proposition for any experimental/therapeutic trial is the uncertainty that the risks of treatment will be outweighed by its benefits. For some therapeutic interventions (e.g., exercise programs, vitamin supplementation), the potential for treatment-emergent adverse events may prima facie be low or negligible, whereas for others…

The evolving landscape of therapeutic drug development for hepatocellular carcinoma.

PubMed

Chong, Dawn Qingqing; Tan, Iain Beehuat; Choo, Su-Pin; Toh, Han Chong

2013-11-01

Currently, only one drug, sorafenib, is FDA approved for the treatment of advanced hepatocellular carcinoma (HCC), achieving modest objective response rates while still conferring an overall survival benefit. Unlike other solid tumors, no oncogenic addiction loops have been validated as clinically actionable targets in HCC. Outcomes of HCC could potentially be improved if critical molecular subclasses with distinct therapeutic vulnerabilities can be identified, biomarkers that predict recurrence or progression early can be determined and key epigenetic, genetic or microenvironment drivers that determine best response to a specific targeting treatment can be uncovered. Our group and others have examined the molecular heterogeneity of hepatocellular carcinoma. We have developed a panel of patient derived xenograft models to enable focused pre-clinical drug development of rationally designed therapies in specific molecular subgroups. We observed unique patterns, including synergies, of drug activity across our molecularly diverse HCC xenografts, pointing to specific therapeutic vulnerabilities for individual tumors. These efforts inform clinical trial designs and catalyze therapeutic development. It also argues for efficient strategic allocation of patients into appropriate enriched clinical trials. Here, we will discuss some of the recent important therapeutic studies in advanced HCC and also some of the potential strategies to optimize clinical therapeutic development moving forward. Copyright © 2013 Elsevier Inc. All rights reserved.

SATPdb: a database of structurally annotated therapeutic peptides

PubMed Central

Singh, Sandeep; Chaudhary, Kumardeep; Dhanda, Sandeep Kumar; Bhalla, Sherry; Usmani, Salman Sadullah; Gautam, Ankur; Tuknait, Abhishek; Agrawal, Piyush; Mathur, Deepika; Raghava, Gajendra P.S.

2016-01-01

SATPdb (http://crdd.osdd.net/raghava/satpdb/) is a database of structurally annotated therapeutic peptides, curated from 22 public domain peptide databases/datasets including 9 of our own. The current version holds 19192 unique experimentally validated therapeutic peptide sequences having length between 2 and 50 amino acids. It covers peptides having natural, non-natural and modified residues. These peptides were systematically grouped into 10 categories based on their major function or therapeutic property like 1099 anticancer, 10585 antimicrobial, 1642 drug delivery and 1698 antihypertensive peptides. We assigned or annotated structure of these therapeutic peptides using structural databases (Protein Data Bank) and state-of-the-art structure prediction methods like I-TASSER, HHsearch and PEPstrMOD. In addition, SATPdb facilitates users in performing various tasks that include: (i) structure and sequence similarity search, (ii) peptide browsing based on their function and properties, (iii) identification of moonlighting peptides and (iv) searching of peptides having desired structure and therapeutic activities. We hope this database will be useful for researchers working in the field of peptide-based therapeutics. PMID:26527728

[From the licensure of vaccines to the recommendation of the Standing Committee on Vaccination in Germany : criteria for the assessment of benefits and risks].

PubMed

Pfleiderer, Michael; Wichmann, Ole

2015-03-01

Vaccines are among the most effective preventive measures in modern medicine and have led to a dramatic decline and-for a few diseases-even to the elimination of severely infectious diseases. There are some particularities of the risk-benefit assessment of vaccines compared with that of therapeutic drugs. These include the fact that vaccines are applied to healthy individuals with the aim of preventing an infectious disease, while therapeutic drugs are administered to sick people to cure them of an already acquired disease. The acceptable level of risk associated with the application of a vaccine is therefore much lower. In addition, high vaccination coverage can lead to population-level effects (e.g., the indirect protection of unvaccinated individuals) that can confer additional benefits to the population overall. When a marketing authorization application (MAA) for a novel vaccine is evaluated, conclusions are made regarding its quality, safety, and efficacy, and a benefit-risk assessment is carried out accordingly. In contrast, when deciding on the introduction of a new vaccine into a national immunization program or on a recommendation for a specific risk-group, the focus is shifted to considerations of how a licensed vaccine can be best used in a population (e.g., which immunization strategy is most effective in preventing deaths or hospitalizations, or in reducing treatment costs for the health care system). Stringent assessment criteria have been developed that require a robust safety analysis before a new vaccine is administered to humans for the first time in pre-licensure studies. Similarly, criteria are applied for calculating the benefit-risk ratio at the time of the licensure of a new vaccine in addition to during the entire post-licensure period. However, when deciding if and how a licensed vaccine can best be integrated into an existing immunization program, additional criteria are applied that are different, yet complementary to those applied for

Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis.

PubMed

Blakeley, Jaishri O; Plotkin, Scott R

2016-05-01

Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are tumor-suppressor syndromes. Each syndrome is an orphan disease; however, the tumors that arise within them represent the most common tumors of the nervous system worldwide. Systematic investigation of the pathways impacted by the loss of function of neurofibromin (encoded byNF1) and merlin (encoded byNF2) have led to therapeutic advances for patients with NF1 and NF2. In the syndrome of SWN, the genetic landscape is more complex, with 2 known causative genes (SMARCB1andLZTR1) accounting for up to 50% of familial SWN patients. The understanding of the molecular underpinnings of these syndromes is developing rapidly and offers more therapeutic options for the patients. In addition, common sporadic cancers harbor somatic alterations inNF1(ie, glioblastoma, breast cancer, melanoma),NF2(ie, meningioma, mesothelioma) andSMARCB1(ie, atypical teratoid/rhabdoid tumors) such that advances in management of syndromic tumors may benefit patients both with and without germline mutations. In this review, we discuss the clinical and genetic features of NF1, NF2 and SWN, the therapeutic advances for the tumors that arise within these syndromes and the interaction between these rare tumor syndromes and the common tumors that share these mutations. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Therapeutic Endoscopic Retrograde Cholangiopancreatography in Pediatric Patients With Acute Recurrent and Chronic Pancreatitis: Data From the INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) Study.

PubMed

Troendle, David M; Fishman, Douglas S; Barth, Bradley A; Giefer, Matthew J; Lin, Tom K; Liu, Quin Y; Abu-El-Haija, Maisam; Bellin, Melena D; Durie, Peter R; Freedman, Steven D; Gariepy, Cheryl; Gonska, Tanja; Heyman, Melvin B; Himes, Ryan; Husain, Sohail Z; Kumar, Soma; Lowe, Mark E; Morinville, Veronique D; Ooi, Chee Y; Palermo, Joseph; Pohl, John F; Schwarzenberg, Sarah Jane; Werlin, Steven; Wilschanski, Michael; Zimmerman, M Bridget; Uc, Aliye

2017-07-01

The aim of this study was to characterize utilization and benefit of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in children with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP). From August 2012 to February 2015, 301 children with ARP or CP were enrolled in the INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) study. Physicians reported utilization and benefit of therapeutic ERCP at enrollment. Differences were analyzed using appropriate statistical methods. One hundred seventeen children (38.9%) underwent at least 1 therapeutic ERCP. The procedure was more commonly performed in children with CP compared with those with ARP (65.8% vs 13.5%, P < 0.0001). Utility of therapeutic ERCP was reported to be similar between ARP and CP (53% vs 56%, P = 0.81) and was found to be helpful for at least 1 indication in both groups (53/99 patients [53.5%]). Predictors for undergoing therapeutic ERCP were presence of obstructive factors in ARP and CP, Hispanic ethnicity, or white race in CP. Therapeutic ERCP is frequently utilized in children with ARP or CP and may offer benefit in selected cases, specifically if ductal obstruction is present. Longitudinal studies are needed to clarify the efficacy of therapeutic ERCP and to explore subgroups that might have increased benefit from such intervention.

Recent Progress in Nanomedicine: Therapeutic, Diagnostic and Theranostic Applications

PubMed Central

Rizzo, Larissa Y.; Theek, Benjamin; Storm, Gert; Kiessling, Fabian; Lammers, Twan

2013-01-01

In recent years, the use of nanomedicine formulations for therapeutic and diagnostic applications has increased exponentially. Many different systems and strategies have been developed for drug targeting to pathological sites, as well as for visualizing and quantifying important (patho-) physiological processes. In addition, ever more efforts have been undertaken to combine diagnostic and therapeutic properties within a single nanomedicine formulation. These so-called nanotheranostics are able to provide valuable information on drug delivery, drug release and drug efficacy, and they are considered to be highly useful for personalizing nanomedicine-based (chemo-) therapeutic interventions. PMID:23578464

Proteases as therapeutics

PubMed Central

Craik, Charles S.; Page, Michael J.; Madison, Edwin L.

2015-01-01

Proteases are an expanding class of drugs that hold great promise. The U.S. FDA (Food and Drug Administration) has approved 12 protease therapies, and a number of next generation or completely new proteases are in clinical development. Although they are a well-recognized class of targets for inhibitors, proteases themselves have not typically been considered as a drug class despite their application in the clinic over the last several decades; initially as plasma fractions and later as purified products. Although the predominant use of proteases has been in treating cardiovascular disease, they are also emerging as useful agents in the treatment of sepsis, digestive disorders, inflammation, cystic fibrosis, retinal disorders, psoriasis and other diseases. In the present review, we outline the history of proteases as therapeutics, provide an overview of their current clinical application, and describe several approaches to improve and expand their clinical application. Undoubtedly, our ability to harness proteolysis for disease treatment will increase with our understanding of protease biology and the molecular mechanisms responsible. New technologies for rationally engineering proteases, as well as improved delivery options, will expand greatly the potential applications of these enzymes. The recognition that proteases are, in fact, an established class of safe and efficacious drugs will stimulate investigation of additional therapeutic applications for these enzymes. Proteases therefore have a bright future as a distinct therapeutic class with diverse clinical applications. PMID:21406063

[Benefit assessment of medical services in German health service - legal framework, historical and international perspective].

PubMed

Windeler, Jürgen; Lange, Stefan

2015-03-01

The term benefit describes the (positive) causal, patient-relevant consequences of medical interventions, whether diagnostic or therapeutic. Benefit assessments form the basis of rational decision-making within a health care system. They are based on clinical trials that are able to provide valid answers to the question regarding the relevant benefit or harm that can be caused by an intervention. In Germany, evidence-based benefit assessments are fixed by law, i.e., the Social Code Book V. The application and the practical impact of these assessments could be improved.

Therapeutic drug monitoring in pregnancy.

PubMed

Matsui, Doreen M

2012-10-01

Therapeutic drug monitoring (TDM) is commonly recommended to optimize drug dosing regimens of various medications. It has been proposed to guide therapy in pregnant women, in whom physiological changes may lead to altered pharmacokinetics resulting in difficulty in predicting the appropriate drug dosage. Ideally, TDM may play a role in enhancing the effectiveness of treatment while minimizing toxicity of both the mother and fetus. Monitoring of drug levels may also be helpful in assessing adherence to prescribed therapy in selected cases. Limitations exist as therapeutic ranges have only been defined for a limited number of drugs and are based on data obtained in nonpregnant patients. TDM has been suggested for anticonvulsants, antidepressants, and antiretroviral drugs, based on pharmacokinetic studies that have shown reduced drug concentrations. However, there is only relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Further studies are required to determine whether implementation of TDM during pregnancy improves outcome and is associated with any benefit beyond that achieved by clinical judgment alone. The cost effectiveness of TDM programs during pregnancy also remains to be examined.

The renaissance of complement therapeutics

PubMed Central

Ricklin, Daniel; Mastellos, Dimitrios C.; Reis, Edimara S.; Lambris, John D.

2018-01-01

The increasing number of clinical conditions that involve a pathological contribution from the complement system — many of which affect the kidneys — has spurred a regained interest in therapeutic options to modulate this host defence pathway. Molecular insight, technological advances, and the first decade of clinical experience with the complement-specific drug eculizumab, have contributed to a growing confidence in therapeutic complement inhibition. More than 20 candidate drugs that target various stages of the complement cascade are currently being evaluated in clinical trials, and additional agents are in preclinical development. Such diversity is clearly needed in view of the complex and distinct involvement of complement in a wide range of clinical conditions, including rare kidney disorders, transplant rejection and haemodialysis-induced inflammation. The existing drugs cannot be applied to all complement-driven diseases, and each indication has to be assessed individually. Alongside considerations concerning optimal points of intervention and economic factors, patient stratification will become essential to identify the best complement-specific therapy for each individual patient. This Review provides an overview of the therapeutic concepts, targets and candidate drugs, summarizes insights from clinical trials, and reflects on existing challenges for the development of complement therapeutics for kidney diseases and beyond. PMID:29199277

Cost-effectiveness of medical nutrition therapy and therapeutically designed meals for older adults with cardiovascular disease.

PubMed

Troyer, Jennifer L; McAuley, William J; McCutcheon, Megan E

2010-12-01

Many older adults experience hyperlipidemia and hypertension, but there is little information about whether medical nutrition therapy (MNT) or therapeutic meals have independent or joint beneficial effects on older adults with these diagnoses. To assess the cost-effectiveness of MNT and therapeutic meals for older adults with hyperlipidemia and/or hypertension. A 1-year prospective four-arm controlled randomized community-based clinical trial. Participants were people ages 60 years or older residing in community settings who were medically diagnosed with either hypertension or hyperlipidemia. They were recruited through a number of venues beginning in May 2003. The 321 eligible individuals were assigned to one of four arms: (a) a literature control group, (b) a therapeutic meal group that received seven diagnosis-appropriate therapeutic meals a week, (c) an MNT group, and (d) an MNT-plus-therapeutic meal group. The outcome measure was quality-adjusted life-years (QALYs). Costs included both intervention and medical costs. Estimations of separate models of costs and QALYs facilitated the construction of incremental cost-effectiveness ratios. Net benefit analysis produced the probability that each intervention was cost-effective given different values for society's willingness to pay for a QALY. Therapeutic meals are cost-effective. Using the net benefit approach and a willingness to pay of $109,000 per QALY, the probability that the therapeutic meal delivery program is cost-effective is 95% and for MNT the probability is 90%. However, the combination of MNT and therapeutic meals did not have an independent significant effect on QALYs. Results inform the debate about extending Medicare funding for MNT to individuals with hypertension and hyperlipidemia. Future research should include more individuals who are not currently receiving medications for these diseases. Copyright © 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.

Neurotrophic factors as a therapeutic target for Parkinson's disease.

PubMed

Evans, Jonathan R; Barker, Roger A

2008-04-01

The search for therapeutic agents that might alter the disease course in Parkinson's disease (PD) is ongoing. One area of particular interest involves neurotrophic factors (NTFs), with those of the glial cell line-derived neurotrophic factor (GDNF) family showing greatest promise. The safety and efficacy of these therapies has recently come into question. Furthermore, many of the key questions pertaining to such therapies, such as the optimal method of delivery, timing of treatment and selection of patients most likely to benefit, remain unanswered. In this review we sought to evaluate the therapeutic potential of NTFs in the treatment of PD. We appraised the evidence provided by both in vitro and in vivo work before proceeding to a critical assessment of the relevant clinical trial data. Relevant literature was identified using a PubMed search of articles published up to October 2007. Search terms included: 'Parkinson's disease', 'Neurotrophic factors', 'BDNF' (Brain-derived neurotrophic factor), 'GDNF' and 'Neurturin'. Original articles were reviewed, and relevant citations from these articles were also appraised. NTF therapy has potential in the treatment of nigrostriatal dysfunction in PD but numerous methodological and safety issues will need to be addressed before this approach can be widely adopted. Furthermore PD is now recognized as being more than a pure motor disorder, and one in which neuronal loss is not just confined to the dopaminergic nigrostriatal system. Non-motor symptomatology in PD is unlikely to benefit from therapies that target only the nigrostriatal system, and this must inform our thinking as to the maximal achievable benefit that NTFs are ever likely to provide.

Bacteria and genetically modified bacteria as cancer therapeutics: Current advances and challenges.

PubMed

Nallar, Shreeram C; Xu, De-Qi; Kalvakolanu, Dhan V

2017-01-01

Bacteria act as pro- or anti- tumorigenic agents. Whole bacteria or cytotoxic or immunogenic peptides carried by them exert potent anti-tumor effects in the experimental models of cancer. The use of attenuated microorganism(s) e.g., BCG to treat human urinary bladder cancer was found to be superior compared to standard chemotherapy. Although the phase-I clinical trials with Salmonella enterica serovar Typhimurium, has shown limited benefits in human subjects, a recent pre-clinical trial in pet dogs with tumors reported some subjects benefited from this treatment strain. In addition to the attenuated host strains derived by conventional mutagenesis, recombinant DNA technology has been applied to a few microorganisms that have been evaluated in the context of tumor colonization and eradication using mouse models. There is an enormous surge in publications describing bacterial anti-cancer therapies in the past 15years. Vectors for delivering shRNAs that target oncogenic products, express tumor suppressor genes and immunogenic proteins have been developed. These approaches have showed promising anti-tumor activity in mouse models against various tumors. These can be potential therapeutics for humans in the future. In this review, some conceptual and practical issues on how to improve these agents for human applications are discussed. Copyright © 2016. Published by Elsevier Ltd.

Your Medicare Benefits

MedlinePlus

... health plans include all Medicare Advantage Plans, Medicare Cost Plans, and Demonstration/Pilot Programs. PACE plans can be offered by public or private entities and provide Part D and other benefits in addition to Part A and Part B ...

42 CFR 61.37 - Stipends, allowances, and benefits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Stipends, allowances, and benefits. 61.37 Section..., INTERNSHIPS, TRAINING FELLOWSHIPS Service Fellowships § 61.37 Stipends, allowances, and benefits. (a) Stipends... employees of the Public Health Service. (c) Benefits. In addition to other benefits provided herein, service...

Biobased lubricant additives

USDA-ARS?s Scientific Manuscript database

Fully biobased lubricants are those formulated using all biobased ingredients, i.e. biobased base oils and biobased additives. Such formulations provide the maximum environmental, safety, and economic benefits expected from a biobased product. Currently, there are a number of biobased base oils that...

Topical antibiotics: therapeutic value or ecologic mischief?

PubMed

Del Rosso, James Q; Kim, Grace K

2009-01-01

Based on antibiotic prescribing data from 2003, dermatologists account annually for 8-9 million prescriptions for oral antibiotics, and 3-4 million prescriptions for topical antibiotics. Overall, much of the emphasis on concerns related to emergence of clinically significant antibiotic-resistant bacterial strains focuses on use of systemic antibiotics, however, topical antibiotic use may also have potential implications. The following article discusses the perspectives of the authors related to the potential therapeutic benefits and ecologic implications ("ecologic mischief") of topical antibiotic therapy for specific indications encountered in ambulatory dermatology practice.

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017.

PubMed

Hiemke, C; Bergemann, N; Clement, H W; Conca, A; Deckert, J; Domschke, K; Eckermann, G; Egberts, K; Gerlach, M; Greiner, C; Gründer, G; Haen, E; Havemann-Reinecke, U; Hefner, G; Helmer, R; Janssen, G; Jaquenoud, E; Laux, G; Messer, T; Mössner, R; Müller, M J; Paulzen, M; Pfuhlmann, B; Riederer, P; Saria, A; Schoppek, B; Schoretsanitis, G; Schwarz, M; Gracia, M Silva; Stegmann, B; Steimer, W; Stingl, J C; Uhr, M; Ulrich, S; Unterecker, S; Waschgler, R; Zernig, G; Zurek, G; Baumann, P

2018-01-01

Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs. © Georg Thieme Verlag KG Stuttgart · New York.

The effects of therapeutic climbing in patients with chronic low back pain: a randomized controlled study.

PubMed

Engbert, Kai; Weber, Michaela

2011-05-15

A randomized controlled study investigated the effects of therapeutic climbing in patients with chronic low back pain. Before and after 4 weeks of training, physical and mental well-being were measured by two questionnaires (36-Item Short Form Health Survey [SF-36]; Hannover Functional Ability Questionnaire for measuring back pain-related disability [FFbH-R]). Therapeutic climbing has been suggested to increase muscular strength and perceived physical and mental well-being. This study focused on the psychological effects of therapeutic climbing and compared it with standard exercise therapy. Therapeutic climbing has become increasingly popular in rehabilitation and its effects on muscular strengthening have been shown. Therapeutic climbing has also been suggested to yield psychological effects such as changes in attentional focus from pain to physical capabilities. To date, no controlled clinical trial has investigated these psychological effects and it is unclear whether therapeutic climbing is comparable or superior to other forms of exercise. Twenty-eight patients with chronic low back pain conducted either a therapeutic climbing or a standard exercise regime. Each program took 4 weeks, including four guided training sessions per week. Before and after the program, patients answered two questionnaires assessing their physical and mental well-being. For the Hannover Functional Ability Questionnaire for measuring back pain-related disability, there was no difference before versus after or between the treatments. For the SF-36, both treatments showed significant improvements in 3/8 subscales of the SF-36. In 2/8 subscales, only the participants of the therapeutic climbing improved and in 1/8 subscales the converse was true. Comparing both groups, significantly larger improvements were found after therapeutic climbing in two subscales of the SF-36: physical functioning and general health perception. The benefits of therapeutic climbing were comparable with those of

20 CFR 416.2035 - Optional supplementation: Additional State options.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Optional supplementation: Additional State options. 416.2035 Section 416.2035 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... § 416.2035 Optional supplementation: Additional State options. (a) Residency requirement. A State or...

The Holy Grail of Polymer Therapeutics for Cancer Therapy: An Overview on the Pharmacokinetics and Bio Distribution.

PubMed

Dyawanapelly, Sathish; Junnuthula, Vijayabhaskar Reddy; Singh, AkhileshVikram

2015-01-01

In recent years, multifaceted clinical benefits of polymeric therapeutics have been reported. Over the past decades, cancer has been one of the leading causes of mortality in the world. Many clinically approved chemotherapeutics encounter potential challenges against deadly cancer. Moreover, safety and efficacy of anticancer agents have been limited by undesirable pharmacokinetics and biodistribution. To address these limitations, various polymer drug conjugates are being studied and developed to improve the antitumor efficacy. Among other therapeutics, polymer therapeutics are well established platforms that circumvent anticancer therapeutics from enzymatic metabolism via direct conjugation to therapeutic molecules. Interestingly, polymer therapeutics meets an unmet need of small molecules. Further clinical study showed that polymer-drug conjugation can achieve desired pharmacokinetics and biodistribution properties of several anticancer drugs. The present retrospective review mainly enlightens the most recent preclinical and clinical studies include safety, stability, pharmacokinetic behavior and distribution of polymer therapeutics.

The effects of therapeutic taping on gross motor function in children with cerebral palsy.

PubMed

Footer, Cheryl Burditt

2006-01-01

Therapeutic taping to address dysfunctional sitting control in children with cerebral palsy (CP) was investigated in this study. Eighteen children with quadriplegic CP, Gross Motor Function Classification System for Cerebral Palsy levels IV (n = 9) and V (n = 9) participated in the 12-week program. Subjects were assigned randomly to one of two groups: therapeutic taping + physical therapy or physical therapy only. Therapeutic taping was applied for periods of up to 72 hours over the paraspinal region. The effects were assessed with the Gross Motor Function Measure (GMFM-88) at baseline, six weeks, and 12 weeks. A factorial analysis of variance was used to examine group differences over time. No significant differences were found for the GMFM-88 scores between groups over time. Therapeutic taping does not evoke a positive functional change in the seated postural control of children with quadriplegic cerebral palsy. Subjective observation, however, suggested that one child with athetosis benefited from therapeutic taping over the paraspinal region.

Risk Factors and Therapeutic Targets in Pancreatic Cancer

PubMed Central

Wörmann, Sonja Maria; Algül, Hana

2013-01-01

Pancreatic cancer (PC) is one of the most challenging tumor entities worldwide, characterized as a highly aggressive disease with dismal overall prognosis and an incidence rate equalling mortality rate. Over the last decade, substantial progress has been made to define the morphological changes and key genetic events in pancreatic carcinogenesis. And yet, it is still unclear what factors trigger PC. Some risk factors appear to be associated with sex, age, race/ethnicity, or other rare genetic conditions. Additionally, modifying factors such as smoking, obesity, diabetes, occupational risk factors, etc., increase the potential for acquiring genetic mutations that may result in PC. Another hallmark of PC is its poor response to radio- and chemo-therapy. Current chemotherapeutic regimens could not provide substantial survival benefit with a clear increase in overall survival. Recently, several new approaches to significantly improve the clinical outcome of PC have been described involving downstream signaling cascades desmoplasia and stromal response as well as tumor microenvironment, immune response, vasculature, and angiogenesis. This review summarizes major risk factors for PC and tries to illuminate relevant targets considerable for new therapeutic approaches. PMID:24303367

Microbiome therapeutics - Advances and challenges.

PubMed

Mimee, Mark; Citorik, Robert J; Lu, Timothy K

2016-10-01

The microbial community that lives on and in the human body exerts a major impact on human health, from metabolism to immunity. In order to leverage the close associations between microbes and their host, development of therapeutics targeting the microbiota has surged in recent years. Here, we discuss current additive and subtractive strategies to manipulate the microbiota, focusing on bacteria engineered to produce therapeutic payloads, consortia of natural organisms and selective antimicrobials. Further, we present challenges faced by the community in the development of microbiome therapeutics, including designing microbial therapies that are adapted for specific geographies in the body, stable colonization with microbial therapies, discovery of clinically relevant biosensors, robustness of engineered synthetic gene circuits and addressing safety and biocontainment concerns. Moving forward, collaboration between basic and applied researchers and clinicians to address these challenges will poise the field to herald an age of next-generation, cellular therapies that draw on novel findings in basic research to inform directed augmentation of the human microbiota. Copyright © 2016. Published by Elsevier B.V.

[Sensory integration: benefits and effectiveness of therapeutic management in sensory processing disorders].

PubMed

Tudela-Torras, M; Abad-Mas, L; Tudela-Torras, E

2017-02-24

Today, the fact that sensory integration difficulties with a neurological basis exist and that they seriously condition the development of those individuals who suffer from them is widely accepted and acknowledged as being obvious by the vast majority of professionals working in the field of community healthcare. However, less is known and there is more controversy about effective treatments that can be applied to them. This is because many professionals criticise the fact that there is not enough scientific evidence to prove, both quantitatively and empirically, the outcomes of the interventions implemented as alternatives to pharmacological therapy. Consequently, when the symptoms and repercussions on the quality of life deriving from a distorted sensory integration are really disabling for the person, pharmacological treatment is used as the only possible approach, with the side effects that this entails. The reason for this is largely the fact that little is known about other effective therapeutic approaches, such as occupational therapy based on sensory integration.

Development of a peptide conjugate vaccine for inducing therapeutic anti-IgE antibodies.

PubMed

Licari, Amelia; Castagnoli, Riccardo; De Sando, Elisabetta; Marseglia, Gian Luigi

2017-04-01

Given the multifaceted effector functions of IgE in immediate hypersensitivity, late-phase reactions, regulation of IgE receptor expression and immune modulation, IgE antibodies have long represented an attractive target for therapeutic agents in asthma and other allergic diseases. Effective pharmacologic blockade of the binding of IgE to its receptors has become one of most innovative therapeutic strategies in the field of allergic diseases in the last 10 years. Areas covered: The latest strategies targeting IgE include the development of a therapeutic vaccine, able to trigger our own immune systems to produce therapeutic anti-IgE antibodies, potentially providing a further step forward in the treatment of allergic diseases. The aim of this review is to discuss the discovery strategy, preclinical and early clinical development of a peptide conjugate vaccine for inducing therapeutic anti-IgE antibodies. Expert opinion: Outside the area of development of humanized anti-IgE monoclonal antibodies, the research field of therapeutic IgE-targeted vaccines holds potential benefits for the treatment of allergic diseases. However, most of the experimental observations in animal models have not yet been translated into new treatments and evidence of human efficacy and safety of this new therapeutic strategy are still lacking.

Therapeutic clinical applications of reactor-produced radioisotopes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knapp, F.F. Jr.

1997-12-01

One of the most rapidly growing areas of clinical nuclear medicine is the therapeutic use of radioisotopes for applications in oncology, rheumatology and, more recently, interventional cardiology. With the rapidly increasing development and evaluation of new agents, their introduction into clinical use, and commercialization, the availability of high levels of therapeutic reactor-produced neutron-rich radioisotopes is of increasing importance. The goals of this paper are to discuss the issues associated with optimization of the production and processing of reactor-produced radioisotopes for therapy, with special emphasis on {sup 188}W, and the optimization of the use of the {sup 188}W/{sup 188}Re generator. Inmore » addition, other key examples of therapeutic radioisotopes of current interest and their specific clinical applications are discussed.« less

Effectiveness of the addition of therapeutic alliance with minimal intervention in the treatment of patients with chronic, nonspecific low back pain and low risk of involvement of psychosocial factors: a study protocol for a randomized controlled trial (TalkBack trial).

PubMed

Fagundes, Felipe Ribeiro Cabral; de Melo do Espírito Santo, Caique; de Luna Teixeira, Francine Mendonça; Tonini, Thaís Vanelli; Cabral, Cristina Maria Nunes

2017-01-31

The stratified model of care has been an effective approach for the treatment of low back pain. However, the treatment of patients with low risk of psychosocial-factor involvement is unclear. The addition of the therapeutic alliance to a minimal intervention may be an option for the treatment of low back pain. This paper reports on the rationale, design and protocol for a randomized controlled trial with blind assessor to assess the effectiveness of the addition of therapeutic alliance with minimal intervention on pain and disability in patients with chronic, nonspecific low back pain. Two hundred and twenty-two patients with chronic, nonspecific low back pain and low risk of involvement of psychosocial factors will be assessed and randomly allocated into three groups (n = 74 patients per group). The Positive Therapeutic Alliance group will receive counseling and guidance with an emphasis on therapeutic alliance and empathy. The Usual Treatment group will receive the same information and counseling with limited interaction with the therapist. The Control group will not receive any intervention. The treatment will be composed by two intervention sessions with a 1-week interval. A blinded assessor will collect the following outcomes at baseline, 1 month, 6 months and 12 months after randomization: pain intensity (Pain Numerical Rating Scale), specific disability (Patient-specific Functional Scale), general disability (Oswestry Disability Index), global perceived effect (Global Perceived Effect Scale), empathy (Consultation and Relational Empathy Measure), credibility and expectations related to treatment. The analysis will be performed using linear mixed models. This will be the first study to understand the effect of combining enhanced therapeutic alliance to a treatment based on counseling, information and advice (minimal intervention). The addition of the therapeutic alliance to minimal intervention may improve the treatment of chronic, nonspecific low back

The potential of prison-based democratic therapeutic communities.

PubMed

Bennett, Jamie; Shuker, Richard

2017-03-13

Purpose The purpose of this paper is to describe the work of HMP Grendon, the only prison in the UK to operate entirely as a series of democratic therapeutic communities and to summarise the research of its effectiveness. Design/methodology/approach The paper is both descriptive, providing an overview of the work of a prison-based therapeutic community, and offers a literature review regarding evidence of effectiveness. Findings The work of HMP Grendon has a wide range of positive benefits including reduced levels of disruption in prison, reduced self-harm, improved well-being, an environment that is experienced as more humane and reduced levels of reoffending. Originality/value The work of HMP Grendon offers a well established and evidenced approach to managing men who have committed serious violent and sexually violent offences. It also promotes and embodies a progressive approach to managing prisons rooted in the welfare tradition.

Therapeutics Targeting FGF Signaling Network in Human Diseases.

PubMed

Katoh, Masaru

2016-12-01

Fibroblast growth factor (FGF) signaling through its receptors, FGFR1, FGFR2, FGFR3, or FGFR4, regulates cell fate, angiogenesis, immunity, and metabolism. Dysregulated FGF signaling causes human diseases, such as breast cancer, chondrodysplasia, gastric cancer, lung cancer, and X-linked hypophosphatemic rickets. Recombinant FGFs are pro-FGF signaling therapeutics for tissue and/or wound repair, whereas FGF analogs and gene therapy are under development for the treatment of cardiovascular disease, diabetes, and osteoarthritis. FGF traps, anti-FGF/FGFR monoclonal antibodies (mAbs), and small-molecule FGFR inhibitors are anti-FGF signaling therapeutics under development for the treatment of cancer, chondrodysplasia, and rickets. Here, I discuss the benefit-risk and cost-effectiveness issues of precision medicine targeting FGFRs, ALK, EGFR, and FLT3. FGFR-targeted therapy should be optimized for cancer treatment, focusing on genomic tests and recurrence. Copyright © 2016 Elsevier Ltd. All rights reserved.

Therapeutic Hypothermia: Critical Review of the Molecular Mechanisms of Action

PubMed Central

González-Ibarra, Fernando Pavel; Varon, Joseph; López-Meza, Elmer G.

2010-01-01

Therapeutic hypothermia (TH) is nowadays one of the most important methods of neuroprotection. The events that occur after an episode of ischemia are multiple and hypothermia can affect the various steps of this cascade. The mechanisms of action of TH are varied and the possible explanation for the benefits of this therapy is probably the multiple mechanisms of action blocking the cascade of ischemia on many levels. TH can affect many metabolic pathways, reactions of inflammation, apoptosis processes, and promote neuronal integrity. To know the mechanisms of action of TH will allow a better understanding about the indications for this therapy and the possibility of searching for other therapies when used in conjunction with hypothermia will provide a therapeutic synergistic effect. PMID:21331282

Therapeutic Hypothermia for Neuroprotection

PubMed Central

Karnatovskaia, Lioudmila V.; Wartenberg, Katja E.

2014-01-01

The earliest recorded application of therapeutic hypothermia in medicine spans about 5000 years; however, its use has become widespread since 2002, following the demonstration of both safety and efficacy of regimens requiring only a mild (32°C-35°C) degree of cooling after cardiac arrest. We review the mechanisms by which hypothermia confers neuroprotection as well as its physiological effects by body system and its associated risks. With regard to clinical applications, we present evidence on the role of hypothermia in traumatic brain injury, intracranial pressure elevation, stroke, subarachnoid hemorrhage, spinal cord injury, hepatic encephalopathy, and neonatal peripartum encephalopathy. Based on the current knowledge and areas undergoing or in need of further exploration, we feel that therapeutic hypothermia holds promise in the treatment of patients with various forms of neurologic injury; however, additional quality studies are needed before its true role is fully known. PMID:24982721

Constipation: Pathophysiology and Current Therapeutic Approaches.

PubMed

Sharma, Amol; Rao, Satish

2017-01-01

Chronic constipation is a common, persistent condition affecting many patients worldwide, presenting significant economic burden and resulting in substantial healthcare utilization. In addition to infrequent bowel movements, the definition of constipation includes excessive straining, a sense of incomplete evacuation, failed or lengthy attempts to defecate, use of digital manoeuvres for evacuation of stool, abdominal bloating, and hard consistency of stools. After excluding secondary causes of constipation, chronic idiopathic or primary constipation can be classified as functional defecation disorder, slow-transit constipation (STC), and constipation-predominant irritable bowel syndrome (IBS-C). These classifications are not mutually exclusive and significant overlap exists. Initial therapeutic approach to primary constipation, regardless of aetiology, consists of diet and lifestyle changes such as encouraging adequate fluid and fibre intake, regular exercise, and dietary modification. Laxatives are the mainstay of pharmacologic treatment for potential long-term therapy in patients who do not respond to lifestyle or dietary modification. After a failed empiric trial of laxatives, diagnostic testing is necessary to understand underlying anorectal and/or colonic pathophysiology. No single test provides a comprehensive assessment for primary constipation; therefore, multiple tests are used to provide complementary information to one another. Dyssynergic defecation, a functional defecation disorder, is an acquired behavioural disorder of defecation present in two-thirds of adult patients, where an inability to coordinate the abdominal, recto-anal, and pelvic floor muscles during attempted defecation exists. Biofeedback therapy is the mainstay treatment for dyssynergic defecation aimed at improving coordination of abdominal and anorectal muscles. A large percentage of patients with dyssynergic defecation also exhibit rectal hyposensitivity and may benefit from the

The Therapeutic School.

ERIC Educational Resources Information Center

Rice, John Steadman

2002-01-01

Contributes to the recent research on specific institutional carriers of the therapeutic culture, such as the state, the corporation, and the self- help movement, defining therapeutic discourse and discussing the therapeutic ethic, the therapeutic school, schools of education and their critics, and disappointing results of therapeutic schooling.…

The Secret Life of Exosomes: What Bees Can Teach Us About Next-Generation Therapeutics.

PubMed

Marbán, Eduardo

2018-01-16

Mechanistic exploration has pinpointed nanosized extracellular vesicles, known as exosomes, as key mediators of the benefits of cell therapy. Exosomes appear to recapitulate the benefits of cells and more. As durable azoic entities, exosomes have numerous practical and conceptual advantages over cells. Will cells end up just being used to manufacture exosomes, or will they find lasting value as primary therapeutic agents? Here, a venerable natural process-the generation of honey-serves as an instructive parable. Flowers make nectar, which bees collect and process into honey. Cells make conditioned medium, which laboratory workers collect and process into exosomes. Unlike flowers, honey is durable, compact, and nutritious, but these facts do not negate the value of flowers themselves. The parallels suggest new ways of thinking about next-generation therapeutics. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Patients With Proneural Glioblastoma May Derive Overall Survival Benefit From the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide: Retrospective Analysis of the AVAglio Trial.

PubMed

Sandmann, Thomas; Bourgon, Richard; Garcia, Josep; Li, Congfen; Cloughesy, Timothy; Chinot, Olivier L; Wick, Wolfgang; Nishikawa, Ryo; Mason, Warren; Henriksson, Roger; Saran, Frank; Lai, Albert; Moore, Nicola; Kharbanda, Samir; Peale, Franklin; Hegde, Priti; Abrey, Lauren E; Phillips, Heidi S; Bais, Carlos

2015-09-01

The AVAglio (Avastin in Glioblastoma) and RTOG-0825 randomized, placebo-controlled phase III trials in newly diagnosed glioblastoma reported prolonged progression-free survival (PFS), but not overall survival (OS), with the addition of bevacizumab to radiotherapy plus temozolomide. To establish whether certain patient subgroups derived an OS benefit from the addition of bevacizumab to first-line standard-of-care therapy, AVAglio patients were retrospectively evaluated for molecular subtype, and bevacizumab efficacy was assessed for each patient subgroup. A total of 349 pretreatment specimens (bevacizumab arm, n = 171; placebo arm, n = 178) from AVAglio patients (total, N = 921) were available for biomarker analysis. Samples were profiled for gene expression and isocitrate dehydrogenase 1 (IDH1) mutation status and classified into previously identified molecular subtypes. PFS and OS were assessed within each subtype. A multivariable analysis accounting for prognostic covariates revealed that bevacizumab conferred a significant OS advantage versus placebo for patients with proneural IDH1 wild-type tumors (17.1 v 12.8 months, respectively; hazard ratio, 0.43; 95% CI, 0.26 to 0.73; P = .002). This analysis also revealed an interaction between the proneural subtype biomarker and treatment arm (P = .023). The group of patients with mesenchymal and proneural tumors derived a PFS benefit from bevacizumab compared with placebo; however, this translated to an OS benefit in the proneural subset only. Retrospective analysis of AVAglio data suggests that patients with IDH1 wild-type proneural glioblastoma may derive an OS benefit from first-line bevacizumab treatment. The predictive value of the proneural subtype observed in AVAglio should be validated in an independent data set. © 2015 by American Society of Clinical Oncology.

Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor

PubMed Central

Gibson, William S.; Jo, Hang Joon; Testini, Paola; Cho, Shinho; Felmlee, Joel P.; Welker, Kirk M.; Klassen, Bryan T.; Min, Hoon-Ki

2016-01-01

Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson’s disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal

Microbiome Therapeutics – Advances and Challenges

PubMed Central

Mimee, Mark; Citorik, Robert J.; Lu, Timothy K.

2016-01-01

The microbial community that lives on and in the human body exerts a major impact on human health, from metabolism to immunity. In order to leverage the close associations between microbes and their host, development of therapeutics targeting the microbiota has surged in recent years. Here, we discuss current additive and subtractive strategies to manipulate the microbiota, focusing on bacteria engineered to produce therapeutic payloads, consortia of natural organisms and selective antimicrobials. Further, we present challenges faced by the community in the development of microbiome therapeutics, including designing microbial therapies that are adapted for specific geographies in the body, stable colonization with microbial therapies, discovery of clinically relevant biosensors, robustness of engineered synthetic gene circuits and addressing safety and biocontainment concerns. Moving forward, collaboration between basic and applied researchers and clinicians to address these challenges will poise the field to herald an age of next-generation, cellular therapies that draw on novel findings in basic research to inform directed augmentation of the human microbiota. PMID:27158095

[Understanding nurses' awareness as to the use of therapeutic play in child care].

PubMed

Maia, Edmara Bazoni Soares; Ribeiro, Circéa Amália; de Borba, Regina Issuzu Hirooka

2011-08-01

The objective of this study was to understand how nurses become aware of the use of therapeutic play as a nursing intervention instrument. Symbolic Interactionism was the theoretical framework and Interpretive Interactionism was used as the methodological framework. Participants were seven nurses working at hospitals and outpatient pediatric units who used the therapeutic play in their practice. Four representative themes emerged: Expanding the way he/she sees the child; Becoming fascinated with a new possibility to provide care; Noticing his/her revalidated action; and Committing himself/herself to the theme development. Such themes revealed that when nurses become acquainted with therapeutic play and use it in his/her practice, they begin on a journey that allows him/her to recognize the benefits of this intervention. By doing so, nurses revalidate their actions more and more, thus valuing play as a nursing intervention tool. The authors believe that teaching about therapeutic play and integrating it to nurses' daily practice are challenges yet to be overcome.

A Benefit-Risk Analysis Approach to Capture Regulatory Decision-Making: Multiple Myeloma.

PubMed

Raju, G K; Gurumurthi, Karthik; Domike, Reuben; Kazandjian, Dickran; Landgren, Ola; Blumenthal, Gideon M; Farrell, Ann; Pazdur, Richard; Woodcock, Janet

2018-01-01

Drug regulators around the world make decisions about drug approvability based on qualitative benefit-risk analysis. In this work, a quantitative benefit-risk analysis approach captures regulatory decision-making about new drugs to treat multiple myeloma (MM). MM assessments have been based on endpoints such as time to progression (TTP), progression-free survival (PFS), and objective response rate (ORR) which are different than benefit-risk analysis based on overall survival (OS). Twenty-three FDA decisions on MM drugs submitted to FDA between 2003 and 2016 were identified and analyzed. The benefits and risks were quantified relative to comparators (typically the control arm of the clinical trial) to estimate whether the median benefit-risk was positive or negative. A sensitivity analysis was demonstrated using ixazomib to explore the magnitude of uncertainty. FDA approval decision outcomes were consistent and logical using this benefit-risk framework. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Therapeutic effects of calcium dobesilate on diabetic nephropathy mediated through reduction of expression of PAI-1

PubMed Central

ZHANG, XIAOQIAN

2013-01-01

The aim of this study was to investigate whether calcium dobesilate (calcium dihydroxy-2,5-benzenesulfonate) may be used to treat diabetic nephropathy. A total of 121 patients with type 2 diabetic nephropathy received calcium dobesilate (500 mg, 3 times a day) for 3 months. The levels of glycated hemoglobin, fasting serum C peptide, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase, γ-glutamyl transferase, urea nitrogen, creatinine, hematocrit, plasma viscosity, whole blood reduced viscosity, high, medium and low shear rate whole blood viscosity, fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and endothelin were determined. The urinary albumin excretion rate (UAER) was also determined once a month during the study. The UAER and medium and low shear rate whole blood viscosity were significantly lower in the treated patients. The rate of microalbuminuria normalization was 90%. During the treatment, the UAERs decreased. The results revealed that calcium dobesilate has therapeutic effects on type 2 diabetes patients with microalbuminuria. In addition, the benefit was positively correlated with the calcium dobesilate treatment time. The therapeutic effect may be due to decreases in the levels of PAI-1. PMID:23251286

Open Mind, Open Heart: An Anthropological Study of the Therapeutics of Meditation Practice in the US

PubMed Central

Myers, Neely; Lewis, Sara; Dutton, MaryAnn

2015-01-01

Based on ethnographic fieldwork and interviews collected with meditation teachers and students in the United States, this article will argue that active training in meditation-based practices occasions the opportunity for people with traumatic stress to develop a stronger mind-body connection through heightened somatic awareness and a focus on the present moment that they find to be therapeutic. Three important themes related to healing through meditation for trauma emerged from the data and centered around the ways our interlocutors attempted to realign their sense of self, mind and body, after a traumatic experience. The themes helped explain why US women perceive meditation as therapeutic for trauma, namely that the practice of meditation enables one to focus on the lived present rather than traumatic memories, to accept pain and “open” one's heart, and to make use of silence instead of speech as a healing modality. As meditation practices increasingly enter global popular culture, promoted for postulated health benefits, the driving question of this research—how meditation may perpetuate human resilience for women who have experienced trauma based on their own perspectives of meditation practices—is a critical addition to the literature. PMID:25613595

Open Mind, Open Heart: An Anthropological Study of the Therapeutics of Meditation Practice in the US.

PubMed

Myers, Neely; Lewis, Sara; Dutton, Mary Ann

2015-09-01

Based on ethnographic fieldwork and interviews collected with meditation teachers and students in the United States, this article will argue that active training in meditation-based practices occasions the opportunity for people with traumatic stress to develop a stronger mind-body connection through heightened somatic awareness and a focus on the present moment that they find to be therapeutic. Three important themes related to healing through meditation for trauma emerged from the data and centered around the ways our interlocutors attempted to realign their sense of self, mind and body, after a traumatic experience. The themes helped explain why US women perceive meditation as therapeutic for trauma, namely that the practice of meditation enables one to focus on the lived present rather than traumatic memories, to accept pain and "open" one's heart, and to make use of silence instead of speech as a healing modality. As meditation practices increasingly enter global popular culture, promoted for postulated health benefits, the driving question of this research--how meditation may perpetuate human resilience for women who have experienced trauma based on their own perspectives of meditation practices--is a critical addition to the literature.

Therapeutic hypothermia in patients following traumatic brain injury: a systematic review.

PubMed

Dunkley, Steven; McLeod, Anne

2017-05-01

The efficacy of therapeutic hypothermia in adult patients with traumatic brain injury is not fully understood. The historical use of therapeutic hypothermia at extreme temperatures was associated with severe complications and led to it being discredited. Positive results from animal studies using milder temperatures led to renewed interest. However, recent studies have not convincingly demonstrated the beneficial effects of therapeutic hypothermia in practice. This review aims to answer the question: in adults with a severe traumatic brain injury (TBI), does the use of therapeutic hypothermia compared with normothermia affect neurological outcome? Systematic review. Four major electronic databases were searched, and a hand search was undertaken using selected key search terms. Inclusion and exclusion criteria were applied. The studies were appraised using a systematic approach, and four themes addressing the research question were identified and critically evaluated. A total of eight peer-reviewed studies were found, and the results show there is some evidence that therapeutic hypothermia may be effective in improving neurological outcome in adult patients with traumatic brain injury. However, the majority of the trials report conflicting results. Therapeutic hypothermia is reported to be effective at lowering intracranial pressure; however, its efficacy in improving neurological outcome is not fully demonstrated. This review suggests that therapeutic hypothermia had increased benefits in patients with haematoma-type injuries as opposed to those with diffuse injury and contusions. It also suggests that cooling should recommence if rebound intracranial hypertension is observed. Although the data indicates a trend towards better neurological outcome and reduced mortality rates, higher quality multi-centred randomized controlled trials are required before therapeutic hypothermia is implemented as a standard adjuvant therapy for treating traumatic brain injury

Therapeutic drug monitoring of antimetabolic cytotoxic drugs

PubMed Central

Lennard, L

1999-01-01

Therapeutic drug monitoring is not routinely used for cytotoxic agents. There are several reasons, but one major drawback is the lack of established therapeutic concentration ranges. Combination chemotherapy makes the establishment of therapeutic ranges for individual drugs difficult, the concentration-effect relationship for a single drug may not be the same as that when the drug is used in a drug combination. Pharmacokinetic optimization protocols for many classes of cytotoxic compounds exist in specialized centres, and some of these protocols are now part of large multicentre trials. Nonetheless, methotrexate is the only agent which is routinely monitored in most treatment centres. An additional factor, especially in antimetabolite therapy, is the existence of pharmacogenetic enzymes which play a major role in drug metabolism. Monitoring of therapy could include assay of phenotypic enzyme activities or genotype in addition to, or instead of, the more traditional measurement of parent drug or drug metabolites. The cytotoxic activities of mercaptopurine and fluorouracil are regulated by thiopurine methyltransferase (TPMT) and dihydropyrimidine dehydrogenase (DPD), respectively. Lack of TPMT functional activity produces life-threatening mercaptopurine myelotoxicity. Very low DPD activity reduces fluorouracil breakdown producing severe cytotoxicity. These pharmacogenetic enzymes can influence the bioavailability, pharmacokinetics, toxicity and efficacy of their substrate drugs. PMID:10190647

[Therapeutic Aggressiveness and Liquid Oncology].

PubMed

Barón Duarte, F J; Rodríguez Calvo, M S; Amor Pan, J R

2017-01-01

Aggressiveness criteria proposed in the scientific literature a decade ago provide a quality judgment and are a reference in the care of patients with advanced cancer, but their use is not generalized in the evaluation of Oncology Services. In this paper we analyze the therapeutic aggressiveness, according to standard criteria, in 1.001 patients with advanced cancer who died in our Institution between 2010 and 2013. The results seem to show that aggressiveness at the end of life is present more frequently than experts recommend. About 25% of patients fulfill at least one criterion of aggressiveness. This result could be explained by a liquid Oncology which does not prioritize the patient as a moral subject in the clinical appointment. Medical care is oriented to necessities and must be articulated in a model focused on dignity and communication. Its implementation through Advanced Care Planning, consideration of patient's values and preferences, and Limitation of therapeutic effort are ways to reduce aggressiveness and improve clinical practice at the end of life. We need to encourage synergic and proactive attitudes, adding the best of cancer research with the best clinical care for the benefit of human being, moral subject and main goal of Medicine.

20 CFR 609.23 - Furnishing additional information.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Furnishing additional information. 609.23 Section 609.23 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR UNEMPLOYMENT COMPENSATION FOR FEDERAL CIVILIAN EMPLOYEES Responsibilities of Federal Agencies § 609.23...

Cost benefit analysis of anti-strip additives in hot mix asphalt with various aggregates.

DOT National Transportation Integrated Search

2015-05-01

This report documents research on moisture sensitivity testing of hot-mix asphalt (HMA) mixes in Pennsylvania and the : associated use of antistrip. The primary objective of the research was to evaluate and compare benefit/cost ratios of mandatory us...

Current Status of Gene Engineering Cell Therapeutics

PubMed Central

Saudemont, Aurore; Jespers, Laurent; Clay, Timothy

2018-01-01

Ex vivo manipulations of autologous patient’s cells or gene-engineered cell therapeutics have allowed the development of cell and gene therapy approaches to treat otherwise incurable diseases. These modalities of personalized medicine have already shown great promises including product commercialization for some rare diseases. The transfer of a chimeric antigen receptor or T cell receptor genes into autologous T cells has led to very promising outcomes for some cancers, and particularly for hematological malignancies. In addition, gene-engineered cell therapeutics are also being explored to induce tolerance and regulate inflammation. Here, we review the latest gene-engineered cell therapeutic approaches being currently explored to induce an efficient immune response against cancer cells or viruses by engineering T cells, natural killer cells, gamma delta T cells, or cytokine-induced killer cells and to modulate inflammation using regulatory T cells. PMID:29459866

42 CFR 422.102 - Supplemental benefits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Supplemental benefits. (a) Mandatory supplemental benefits. (1) Subject to CMS approval, an MA organization may require Medicare enrollees of an MA plan (other than an MSA plan) to accept or pay for services in addition to Medicare-covered services described in § 422.101. (2) If the MA organization imposes mandatory...

Sleep Physiology, Abnormal States, and Therapeutic Interventions

PubMed Central

Wickboldt, Alvah T.; Bowen, Alex F.; Kaye, Aaron J.; Kaye, Adam M.; Rivera Bueno, Franklin; Kaye, Alan D.

2012-01-01

Sleep is essential. Unfortunately, a significant portion of the population experiences altered sleep states that often result in a multitude of health-related issues. The regulation of sleep and sleep-wake cycles is an area of intense research, and many options for treatment are available. The following review summarizes the current understanding of normal and abnormal sleep-related conditions and the available treatment options. All clinicians managing patients must recommend appropriate therapeutic interventions for abnormal sleep states. Clinicians' solid understanding of sleep physiology, abnormal sleep states, and treatments will greatly benefit patients regardless of their disease process. PMID:22778676

Amendments to excepted benefits. Final rules.

PubMed

2014-10-01

This document contains final regulations that amend the regulations regarding excepted benefits under the Employee Retirement Income Security Act of 1974, the Internal Revenue Code (the Code), and the Public Health Service Act. Excepted benefits are generally exempt from the health reform requirements that were added to those laws by the Health Insurance Portability and Accountability Act and the Patient Protection and Affordable Care Act. In addition, eligibility for excepted benefits does not preclude an individual from eligibility for a premium tax credit under section 36B of the Code if an individual chooses to enroll in coverage under a Qualified Health Plan through an Affordable Insurance Exchange. These regulations finalize some but not all of the proposed rules with minor modifications; additional guidance on limited wraparound coverage is forthcoming.

Drug Vaping: From the Dangers of Misuse to New Therapeutic Devices

PubMed Central

Varlet, V.

2016-01-01

Users of e-cigarettes are unwitting volunteers participating in a worldwide epidemiological study. Because of the obvious benefits of e-cigarettes compared with traditional cigarette smoking, these electronic devices have been introduced all around the world to support tobacco smoking cessation. Same potential harm reduction could be considered by cannabis vaping for marijuana smokers. However, the toxicities of liquids and aerosols remain under investigation because although the use of e-cigarettes is likely to be less harmful than traditional cigarette smoking, trace levels of contaminants have been identified. Simultaneously, other electronic devices, such as e-vaporisers, e-hookahs or e-pipes, have been developed and commercialised. Consequently, misuse of electronic devices has increased, and experimentation has been documented on Internet web fora. Although legal and illegal drugs are currently consumed with these e-devices, no scientific papers are available to support the observations reported by numerous media and web fora. Moreover, building on illegal drug vaping and vaporisation with e-devices (vaping misuse), legal drug vaping (an alternative use of vaping) could present therapeutic benefits, as occurs with medical cannabis vaporisation with table vaporisers. This review seeks to synthesise the problems of e-cigarette and liquid refill toxicity in order to introduce the dangers of illegal and legal drugs consumed using vaping and vaporisation for recreational purposes, and finally, to present the potential therapeutic benefits of vaping as a new administration route for legal drugs. PMID:29051432

Drug Vaping: From the Dangers of Misuse to New Therapeutic Devices.

PubMed

Varlet, V

2016-12-16

Users of e-cigarettes are unwitting volunteers participating in a worldwide epidemiological study. Because of the obvious benefits of e-cigarettes compared with traditional cigarette smoking, these electronic devices have been introduced all around the world to support tobacco smoking cessation. Same potential harm reduction could be considered by cannabis vaping for marijuana smokers. However, the toxicities of liquids and aerosols remain under investigation because although the use of e-cigarettes is likely to be less harmful than traditional cigarette smoking, trace levels of contaminants have been identified. Simultaneously, other electronic devices, such as e-vaporisers, e-hookahs or e-pipes, have been developed and commercialised. Consequently, misuse of electronic devices has increased, and experimentation has been documented on Internet web fora. Although legal and illegal drugs are currently consumed with these e-devices, no scientific papers are available to support the observations reported by numerous media and web fora. Moreover, building on illegal drug vaping and vaporisation with e-devices (vaping misuse), legal drug vaping (an alternative use of vaping) could present therapeutic benefits, as occurs with medical cannabis vaporisation with table vaporisers. This review seeks to synthesise the problems of e-cigarette and liquid refill toxicity in order to introduce the dangers of illegal and legal drugs consumed using vaping and vaporisation for recreational purposes, and finally, to present the potential therapeutic benefits of vaping as a new administration route for legal drugs.

Additives to local anesthetics for peripheral nerve blocks: Evidence, limitations, and recommendations.

PubMed

Bailard, Neil S; Ortiz, Jaime; Flores, Roland A

2014-03-01

The therapeutic rationale, clinical effectiveness, and potential adverse effects of medications used in combination with local anesthetics for peripheral nerve block therapy are reviewed. A wide range of agents have been tested as adjuncts to peripheral nerve blocks, which are commonly performed for regional anesthesia during or after hand or arm surgery, neck or spine surgery, and other procedures. Studies to determine the comparative merits of nerve block adjuncts are complicated by the wide variety of coadministered local anesthetics and sites of administration and by the heterogeneity of primary endpoints. Sodium bicarbonate has been shown to speed the onset of mepivacaine nerve blocks but delay the onset of others. Epinephrine has been shown to prolong sensory nerve blockade and delay systemic uptake of local anesthetics, thus reducing the risk of anesthetic toxicity. Tramadol, buprenorphine, dexamethasone, and clonidine appear to be effective additives in some situations. Midazolam, magnesium, dexmedetomidine, and ketamine cannot be routinely recommended as nerve block additives due to a dearth of supportive data, modest efficacy, and (in the case of ketamine) significant adverse effects. Recent studies suggest that administering additives intravenously or intramuscularly can provide many of the benefits of perineural administration while reducing the potential for neurotoxicity, contamination, and other hazards. Some additives to local anesthetics can hasten the onset of nerve block, prolong block duration, or reduce toxicity. On the other hand, poorly selected or unnecessary additives may not have the desired effect and may even expose patients to unnecessary risks.

Therapeutic Uses of Triphala in Ayurvedic Medicine.

PubMed

Peterson, Christine Tara; Denniston, Kate; Chopra, Deepak

2017-08-01

The aim of this article is to review the current literature on the therapeutic uses and efficacy of Triphala. Herbal remedies are among the most ancient medicines used in traditional systems of healthcare such as Ayurveda. Triphala, a well-recognized and highly efficacious polyherbal Ayurvedic medicine consisting of fruits of the plant species Emblica officinalis (Amalaki), Terminalia bellerica (Bibhitaki), and Terminalia chebula (Haritaki), is a cornerstone of gastrointestinal and rejuvenative treatment. A search of the PubMed database was conducted. In addition, numerous additional therapeutic uses described both in the Ayurvedic medical literature and anecdotally are being validated scientifically. In addition to laxative action, Triphala research has found the formula to be potentially effective for several clinical uses such as appetite stimulation, reduction of hyperacidity, antioxidant, anti-inflammatory, immunomodulating, antibacterial, antimutagenic, adaptogenic, hypoglycemic, antineoplastic, chemoprotective, and radioprotective effects, and prevention of dental caries. Polyphenols in Triphala modulate the human gut microbiome and thereby promote the growth of beneficial Bifidobacteria and Lactobacillus while inhibiting the growth of undesirable gut microbes. The bioactivity of Triphala is elicited by gut microbiota to generate a variety of anti-inflammatory compounds. This review summarizes recent data on pharmacological properties and clinical effects of Triphala while highlighting areas in need of additional investigation and clinical development.

Angolan Cymbopogon citratus used for therapeutic benefits: nutritional composition and influence of solvents in phytochemicals content and antioxidant activity of leaf extracts.

PubMed

Soares, Marta O; Alves, Rita C; Pires, Pedro C; Oliveira, M Beatriz P P; Vinha, Ana F

2013-10-01

Folk medicine is a relevant and effective part of indigenous healthcare systems which are, in practice, totally dependent on traditional healers. An outstanding coincidence between indigenous medicinal plant uses and scientifically proved pharmacological properties of several phytochemicals has been observed along the years. This work focused on the leaves of a medicinal plant traditionally used for therapeutic benefits (Angolan Cymbopogon citratus), in order to evaluate their nutritional value. The bioactive phytochemical composition and antioxidant activity of leaf extracts prepared with different solvents (water, methanol and ethanol) were also evaluated. The plant leaves contained ∼60% of carbohydrates, protein (∼20%), fat (∼5%), ash (∼4%) and moisture (∼9%). The phytochemicals screening revealed the presence of tannins, flavonoids, and terpenoids in all extracts. Methanolic extracts also contained alkaloids and steroids. Several methods were used to evaluate total antioxidant capacity of the different extracts (DPPH·, NO·, and H₂O₂ scavenging assays, reducing power, and FRAP). Ethanolic extracts presented a significantly higher antioxidant activity (p<0.05) except for FRAP, in which the best results were achieved by the aqueous extracts. Methanolic extracts showed the lowest radical scavenging activities for both DPPH· and NO· radicals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Lipid-lowering therapy: who can benefit?

PubMed

Lewis, Sandra J

2011-01-01

Cardiovascular disease (CVD) is the leading cause of death in the US. Despite the decline in CVD-associated mortality rates in recent years, coronary heart disease (CHD) still causes one in every six deaths in this country. Because most CHD risk factors are modifiable (eg, smoking, hypertension, obesity, onset of type 2 diabetes, and dyslipidemia), cardiovascular risk can be reduced by timely and appropriate interventions, such as smoking cessation, diet and lifestyle changes, and lipid-modifying therapy. Dyslipidemia, manifested by elevated low-density lipoprotein cholesterol (LDL-C), is central to the development and progression of atherosclerosis, which can be silent for decades before triggering a first major cardiovascular event. Consequently, dyslipidemia has become a primary target of intervention in strategies for the prevention of cardiovascular events. The guidelines of the Adult Treatment Panel (ATP) III, updated in 2004, recommend therapeutic lifestyle changes and the use of lipid-lowering medications, such as statins, to achieve specific LDL-C goals based on a person's global cardiovascular risk. For high-risk individuals, such as patients with CHD and diabetic patients without CHD, an LDL-C target of < 100 mg/dL is recommended, and statin therapy should be considered to help patients achieve this goal. If correctly dosed in appropriate patients, currently approved statins are generally safe and provide significant cardiovascular benefits in diverse populations, including women, the elderly, and patients with diabetes. A recent primary prevention trial also showed that statins benefit individuals traditionally not considered at high risk of CHD, such as those with no hyperlipidemia but elevated C-reactive protein. Additional evidence suggests that statins may halt or slow atherosclerotic disease progression. Recent evidence confirms the pivotal role of statins in primary and secondary prevention.

Population genetics and benefit sharing.

PubMed

Knoppers, B M

2000-01-01

The majority of international or national guidelines, specific to human genetics concentrate on actual or potential clinical applications. In contrast, the Ethics Committee of the Human Genome Organisation (HUGO) attempts to provide guidance to the bench scientists engaged in fundamental research in genomics prior to any clinical applications. Often confused as constituting the Human Genome Project (HGP) itself, HUGO's (Human Genome Organization) ultimate goal is to assist in the worldwide collaboration underpinning the HGP. It is an international organisation with 1,229 members in approximately 60 countries. The Ethics Committee is one of HUGO's six international advisory committees. Composed of experts from a number of countries and disciplines, the HUGO Ethics Committee promotes discussion and understanding of social, legal, and ethical issues as they relate to the conduct of, and knowledge derived from, the Genome Initiative. Currently, it has 13 members from 11 difference countries. It has produced statements on the conduct of genetic research, on cloning, and, has most recently presented a 'Statement on Benefit-Sharing', April 11, 2000. The Intellectual Property Committee of HUGO has been active in the controversial area of patenting. The issue of benefit-sharing is one that has its source in the mandate of both committees. How to avoid both commodification of the person through payment for access to DNA and biopiracy with no return to benefits to the families or community? While patents are a legitimate form of recognition for innovation, there seems to be no therapeutic exception to some of its stringent rules and the 'morality' exclusion has lain dormant. The HUGO 'Statement on Benefit-Sharing' examines the issues of defining community, common heritage, distributive justice and solidarity before arriving at its conclusions in benefit-sharing. This communication reviews some of these issues.

20 CFR 404.1919 - How benefits are recomputed.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false How benefits are recomputed. 404.1919 Section 404.1919 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY... will recompute the pro rata PIA only if the inclusion of the additional earnings results in an increase...

Prospects for Therapeutic Tolerance in Humans

PubMed Central

Baker, Kenneth F; Isaacs, John D

2015-01-01

Purpose of review To provide an overview of recent advances and future possibilities for therapeutic tolerance. Recent findings Allograft survival despite complete immunosuppressant withdrawal has been demonstrated in selected renal transplant recipients with haematopoietic chimerism. Early clinical trials of mesenchymal stromal cell therapy have shown promising results in several autoimmune diseases. Regulatory T-cells show potential benefit in graft versus host disease, although challenges to ex vivo expansion remain. Targeted modulation of T-cell function in vivo with monoclonal antibodies have shown beneficial effects in phase II/III trials of multiple sclerosis (alemtuzumab) and type I diabetes mellitus (teplizumab, otelixizumab). Emerging data from animal models suggests an important role for the commensal microbiome in the maintenance and disruption of immune tolerance with parallels in human studies. Summary After years of slow progress, recent research has reduced the translational gap between animal models and clinical therapeutic tolerance. Early detection of autoimmunity, potentially at preclinical stages, offers a window of opportunity for tolerogenic therapy. Reliable biomarkers of tolerance are urgently needed to provide objective measurements of the effectiveness of tolerogenic therapies, and to allow for intelligent immunosuppressant withdrawal in patients whose autoimmune disease is stable. Video Abstract PMID:24378931

Therapeutic Amenorrhea in Patients at Risk for Thrombocytopenia

PubMed Central

Martin-Johnston, Meredith K.; Okoji, Olanma Y.; Armstrong, Alicia

2016-01-01

To examine the need for and evaluate the method of menses suppression in women at risk for thrombocytopenia. A systematic review of the published literature in MEDLINE using the search terms thrombocytopenia, menorrhagia, therapeutic amenorrhea, progestin intrauterine device, combination oral contraceptive—extended and cyclic, gonadotropin releasing hormone agonist, danazol, and progestins. There are an increased number of reproductive age women at risk for thrombocytopenia who would benefit from menses suppression. A number of effective medical regimens are available. In patients who fail medical therapy, endometrial ablation appears to be effective in women with thrombocytopenia. As a result of the increased number of women at risk for thrombocytopenia, there is a need for therapeutic amenorrhea. The type of regimen selected depends upon the patients need for contraception and the ability to tolerate estrogen-containing medications. For women who fail medical therapy, there are surgical options, which are associated with less morbidity than hysterectomy. PMID:18492296

Preclinical evaluation of potential therapeutic targets in dedifferentiated liposarcoma.

PubMed

Hanes, Robert; Grad, Iwona; Lorenz, Susanne; Stratford, Eva W; Munthe, Else; Reddy, Chilamakuri Chandra Sekhar; Meza-Zepeda, Leonardo A; Myklebost, Ola

2016-08-23

Sarcomas are rare cancers with limited treatment options. Patients are generally treated by chemotherapy and/or radiotherapy in combination with surgery, and would benefit from new personalized approaches. In this study we demonstrate the potential of combining personal genomic characterization of patient tumors to identify targetable mutations with in vitro testing of specific drugs in patient-derived cell lines. We have analyzed three metastases from a patient with high-grade metastatic dedifferentiated liposarcoma (DDLPS) by exome and transcriptome sequencing as well as DNA copy number analysis. Genomic aberrations of several potentially targetable genes, including amplification of KITLG and FRS2, in addition to amplification of CDK4 and MDM2, characteristic of this disease, were identified. We evaluated the efficacy of drugs targeting these aberrations or the corresponding signaling pathways in a cell line derived from the patient. Interestingly, the pan-FGFR inhibitor NVP-BGJ398, which targets FGFR upstream of FRS2, strongly inhibited cell proliferation in vitro and induced an accumulation of cells into the G0 phase of the cell cycle. This study indicates that FGFR inhibitors have therapeutic potential in the treatment of DDLPS with amplified FRS2.

Therapeutic Affordances of Online Support Group Use in Women With Endometriosis

PubMed Central

2016-01-01

Background The Internet has provided women living with endometriosis new opportunities to seek support online. Online support groups may provide a range of therapeutic affordances that may benefit these women. Objective To examine the presence of therapeutic affordances as perceived by women who use endometriosis online support groups. Methods Sixty-nine women (aged 19-50 years, mean 34.2 years; 65.2% (45/69) United Kingdom, 21.7% (15/69) United States) participated in a Web-based interview exploring online support group use. Participants had been using online support groups for an average of 2 years and 4 months (range = 1 month to 14 years, 9 months). Responses were analyzed using inductive thematic analysis. Results The analysis revealed 4 therapeutic affordances related to online support group use: (1) “connection,” that is, the ability to connect in order to support each other, exchange advice, and to try to overcome feelings of loneliness; (2) “exploration,” that is, the ability to look for information, learn, and bolster their knowledge; (3) “narration,” that is, the ability to share their experiences, as well as read about the experiences of others; and (4) “self-presentation,” that is, the ability to manage how they present themselves online. The associated outcomes of use were predominantly positive, such as reassurance and improved coping. However, a number of negative aspects were revealed including the following: concerns about the accuracy of information, arguments between members, overreliance on the group, becoming upset by negative experiences or good news items, and confidentiality of personal information. Conclusions Our findings support the previously proposed SCENA (Self-presentation, Connection, Exploration, Narration, and Adaptation) model and reveal a range of positive aspects that may benefit members, particularly in relation to reassurance and coping. However, negative aspects need to be addressed to maximize the potential

Recommendations for research priorities in breast cancer by the Coalition of Cancer Cooperative Groups Scientific Leadership Council: systemic therapy and therapeutic individualization.

PubMed

Sparano, Joseph A; Hortobagyi, Gabriel N; Gralow, Julie R; Perez, Edith A; Comis, Robert L

2010-02-01

Over 9,000 women with breast cancer are enrolled annually on clinical trials sponsored by the National Cancer Institute (NCI), accounting for about one-third of all patients enrolled on NCI-sponsored trials. Thousands are also enrolled on pharmaceutical-sponsored studies. Although breast cancer mortality rates have recently declined for the first time in part due to systemic therapeutic advances, coordinated efforts will be necessary to maintain this trend. The Coalition of Cancer Cooperative Groups convened the Scientific Leadership Council in breast cancer (BC), an expert panel, to identify priorities for future research and current trials with greatest practice-changing potential. Panelists formed a consensus on research priorities for chemoprevention, development and application of molecular markers for predicting therapeutic benefit and toxicity, intermediate markers predictive of therapeutic effect, pathogenesis-based therapeutic approaches, utilization of adaptive designs requiring fewer patients to achieve objectives, special and minority populations, and effects of BC and treatment on patients and families. Panelists identified 13 ongoing studies as High Priority and identified gaps in the current trial portfolio. We propose priorities for current and future clinical breast cancer research evaluating systemic therapies that may serve to improve the efficiency of clinical trials, identify individuals most likely to derive therapeutic benefit, and prioritize therapeutic strategies.

Advances in therapeutic vaccines for pancreatic cancer.

PubMed

Plate, Janet M D

2012-08-01

Pancreatic cancer is one of the most difficult-to-treat cancers. Despite surgical resection, radiation and/or chemotherapy, greater than 94% of people with pancreatic cancer do not survive beyond 5 years. In fact, median survival after diagnosis of metastatic pancreatic cancer is 4.5 months. The majority of patients are diagnosed with nonresectable, metastatic disease, and chemotherapy only extends their median survival by less than 2 months with only 18% of those treated surviving beyond 1 year. Despite the severity of their disease, most patients exhibit tumor specific cellular immunity to their pancreatic cancer antigens. Obviously their immunity is ineffective in preventing tumor growth. Recent studies have demonstrated that the tumor microenvironment may hold the key to determining the nature of the tumors' ability to escape from immune attack. Preliminary clinical trials have suggested that blocking these escape mechanisms may result in survival benefit to the patients, and phase I and II clinical trials with tumor vaccines have led to some survival benefits. Perhaps combining therapies directed against immune escape mechanisms with tumor vaccines will result in even greater survival benefit for patients with pancreatic cancer. While therapeutic vaccines for pancreatic cancers have been reviewed previously (Plate, 2011), updates on recent preliminary reports of two clinical vaccine trials are worthy of our attention.

Current progress on aptamer-targeted oligonucleotide therapeutics

PubMed Central

Dassie, Justin P; Giangrande, Paloma H

2014-01-01

Exploiting the power of the RNAi pathway through the use of therapeutic siRNA drugs has remarkable potential for treating a vast array of human disease conditions. However, difficulties in delivery of these and similar nucleic acid-based pharmacological agents to appropriate organs or tissues, remains a major impediment to their broad clinical application. Synthetic nucleic acid ligands (aptamers) have emerged as effective delivery vehicles for therapeutic oligonucleotides, including siRNAs. In this review, we summarize recent attractive developments in creatively employing cell-internalizing aptamers to deliver therapeutic oligonucleotides (e.g., siRNAs, miRNAs, anti-miRs and antisense oligos) to target cells. We also discuss advancements in aptamer-siRNA chimera technology, as well as, aptamer-functionalized nanoparticles for siRNA delivery. In addition, the challenges and future prospects of aptamer-targeted oligonucleotide drugs for clinical translation are further highlighted. PMID:24304250

Pharmacokinetic and pharmacodynamic considerations for the next generation protein therapeutics.

PubMed

Shah, Dhaval K

2015-10-01

Increasingly sophisticated protein engineering efforts have been undertaken lately to generate protein therapeutics with desired properties. This has resulted in the discovery of the next generation of protein therapeutics, which include: engineered antibodies, immunoconjugates, bi/multi-specific proteins, antibody mimetic novel scaffolds, and engineered ligands/receptors. These novel protein therapeutics possess unique physicochemical properties and act via a unique mechanism-of-action, which collectively makes their pharmacokinetics (PK) and pharmacodynamics (PD) different than other established biological molecules. Consequently, in order to support the discovery and development of these next generation molecules, it becomes important to understand the determinants controlling their PK/PD. This review discusses the determinants that a PK/PD scientist should consider during the design and development of next generation protein therapeutics. In addition, the role of systems PK/PD models in enabling rational development of the next generation protein therapeutics is emphasized.

Pharmacokinetic and pharmacodynamic considerations for the next generation protein therapeutics

PubMed Central

Shah, Dhaval K.

2015-01-01

Increasingly sophisticated protein engineering efforts have been undertaken lately to generate protein therapeutics with desired properties. This has resulted in the discovery of the next generation of protein therapeutics, which include: engineered antibodies, immunoconjugates, bi/multi-specific proteins, antibody mimetic novel scaffolds, and engineered ligands/receptors. These novel protein therapeutics possess unique physicochemical properties and act via a unique mechanism-of-action, which collectively makes their pharmacokinetics (PK) and pharmacodynamics (PD) different than other established biological molecules. Consequently, in order to support the discovery and development of these next generation molecules, it becomes important to understand the determinants controlling their PK/PD. This review discusses the determinants that a PK/PD scientist should consider during the design and development of next generation protein therapeutics. In addition, the role of systems PK/PD models in enabling rational development of the next generation protein therapeutics is emphasized. PMID:26373957

Therapeutic options to treat sulfur mustard poisoning--the road ahead.

PubMed

Smith, William J

2009-09-01

For the past 15 years the international research community has conducted a basic and applied research program aimed at identifying a medical countermeasure against chemical threat vesicant, or blistering, agents. The primary emphasis of this program has been the development of therapeutic protection against sulfur mustard and its cutaneous pathology-blister formation. In addition to the work on a medical countermeasures, significant research has been conducted on the development of topical skin protectants and medical strategies for wound healing. This review will focus on the pharmacological strategies investigated, novel therapeutic targets currently under investigation and therapeutic approaches being considered for transition to advanced development. Additionally, we will review the expansion of our understanding of the pathophysiological mechanisms of mustard injury that has come from this research. While great strides have been made through these investigations, the complexity of the mustard insult demands that further studies extend the inroads made and point the way toward better understanding of cellular and tissue disruptions caused by sulfur mustard.

Do drug advertisements provide therapeutic information?

PubMed Central

Stimson, G V

1977-01-01

In this study of advertisements appearing in medical periodicals and by direct mail advertising to general practitioners, Dr. Stimson, a sociologist, concludes that from what is intended to provide therapeutic information hardly any therapeutic information is provided. He reminds the reader of the safeguards which surround all drug advertising by law and by the code of practice of the Association of the British Pharmaceutical Industry but these safeguards do not appear to control real or potential sins of omission. Frequently in these advertisements the literature relating to the drug is quoted but Dr. Stimson found that it was difficult to trace all the papers quoted in different types of medical library. (Some references quoted were to unpublished papers but surely the blame should be shared in this situation?) Dr. Stimson also gives a vivid and fascinating glimpse of what he calls the 'images and stereotypes' of the patients who, it is claimed, would benefit from the drug being advertised. Certainly most general practitioners must be aware that when they prescribe that image is displaced by an individual but the portrait gallery is indeed depressing. However, to balance these advertisements drug companies issue data sheets which must be more informative than advertisements and conform to regulations in their format. Unfortunately data sheets are only issued every 15 months whereas the 'average general practitioner is potentially exposed to 1,300 advertisements every month'. In other words, the data sheet and not the advertisement should be the guideline but it arrives too infrequently to offset the lack of therapeutic information contained in advertisements. PMID:870694

Therapeutic affect reduction, emotion regulation, and emotional memory reconsolidation: A neuroscientific quandary.

PubMed

LaBar, Kevin S

2015-01-01

Lane et al. emphasize the role of emotional arousal as a precipitating factor for successful psychotherapy. However, as therapy ensues, the arousal diminishes. How can the unfolding therapeutic process generate long-term memories for reconsolidated emotional material without the benefit of arousal? Studies investigating memory for emotionally regulated material provide some clues regarding the neural pathways that may underlie therapy-based memory reconsolidation.

Discovery and design of carbohydrate-based therapeutics.

PubMed

Cipolla, Laura; Araújo, Ana C; Bini, Davide; Gabrielli, Luca; Russo, Laura; Shaikh, Nasrin

2010-08-01

Till now, the importance of carbohydrates has been underscored, if compared with the two other major classes of biopolymers such as oligonucleotides and proteins. Recent advances in glycobiology and glycochemistry have imparted a strong interest in the study of this enormous family of biomolecules. Carbohydrates have been shown to be implicated in recognition processes, such as cell-cell adhesion, cell-extracellular matrix adhesion and cell-intruder recognition phenomena. In addition, carbohydrates are recognized as differentiation markers and as antigenic determinants. Due to their relevant biological role, carbohydrates are promising candidates for drug design and disease treatment. However, the growing number of human disorders known as congenital disorders of glycosylation that are being identified as resulting from abnormalities in glycan structures and protein glycosylation strongly indicates that a fast development of glycobiology, glycochemistry and glycomedicine is highly desirable. The topics give an overview of different approaches that have been used to date for the design of carbohydrate-based therapeutics; this includes the use of native synthetic carbohydrates, the use of carbohydrate mimics designed on the basis of their native counterpart, the use of carbohydrates as scaffolds and finally the design of glyco-fused therapeutics, one of the most recent approaches. The review covers mainly literature that has appeared since 2000, except for a few papers cited for historical reasons. The reader will gain an overview of the current strategies applied to the design of carbohydrate-based therapeutics; in particular, the advantages/disadvantages of different approaches are highlighted. The topic is presented in a general, basic manner and will hopefully be a useful resource for all readers who are not familiar with it. In addition, in order to stress the potentialities of carbohydrates, several examples of carbohydrate-based marketed therapeutics are given

Bioactive compounds of sea cucumbers and their therapeutic effects

NASA Astrophysics Data System (ADS)

Shi, Shujuan; Feng, Wenjing; Hu, Song; Liang, Shixiu; An, Nina; Mao, Yongjun

2016-05-01

Sea cucumbers belong to the Class Holothuroidea of marine invertebrates. They are commercially valuable and prized as a food and folk medicine in Asia. Nutritionally, sea cucumbers have an impressive profile of valuable nutrients such as vitamins, minerals and amino acids. A number of unique biological and pharmacological activities/properties, including anticancer, anticoagulant/antithrombotic, antimicrobial, antioxidant, antihyperlipidemic, antihyperglycemic, anti-inflammatory, antihypertension and radioprotective, have been ascribed to various compounds isolated from sea cucumbers. The therapeutic properties and medicinal benefits of sea cucumbers can be linked to the presence of a wide array of bioactives, especially triterpene glycosides, acid mucopolysaccharide, sphingoid bases, glycolipids, fucosylated chondroitin sulfate, polysaccharides, phospholipids, cerebrosides, phosphatidylcholines, and other extracts and hydrolysates. This review highlights the valuable bioactive components as well as the multiple therapeutic properties of sea cucumbers with a view to exploring their potential uses as functional foods and a natural source of new multifunctional drugs.

20 CFR 416.805 - When additional evidence may be required.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false When additional evidence may be required. 416.805 Section 416.805 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Determination of Age § 416.805 When additional evidence may be...

Optimizing oncology therapeutics through quantitative translational and clinical pharmacology: challenges and opportunities.

PubMed

Venkatakrishnan, K; Friberg, L E; Ouellet, D; Mettetal, J T; Stein, A; Trocóniz, I F; Bruno, R; Mehrotra, N; Gobburu, J; Mould, D R

2015-01-01

Despite advances in biomedical research that have deepened our understanding of cancer hallmarks, resulting in the discovery and development of targeted therapies, the success rates of oncology drug development remain low. Opportunities remain for objective dose selection informed by exposure-response understanding to optimize the benefit-risk balance of novel therapies for cancer patients. This review article discusses the principles and applications of modeling and simulation approaches across the lifecycle of development of oncology therapeutics. Illustrative examples are used to convey the value gained from integration of quantitative clinical pharmacology strategies from the preclinical-translational phase through confirmatory clinical evaluation of efficacy and safety. © 2014 American Society for Clinical Pharmacology and Therapeutics.

Therapeutic interventions in cerebral palsy.

PubMed

Patel, Dilip R

2005-11-01

Various therapeutic interventions have been used in the management of children with cerebral palsy. Traditional physiotherapy and occupational therapy are widely used interventions and have been shown to be of benefit in the treatment of cerebral palsy. Evidence in support of the effectiveness of the neurodevelopmental treatment is equivocal at best. There is evidence to support the use and effectiveness of neuromuscular electrical stimulation in children with cerebral palsy. The effectiveness of many other interventions used in the treatment of cerebral palsy has not been clearly established based on well-controlled trials. These include: sensory integration, body-weight support treadmill training, conductive education, constraint-induced therapy, hyperbaric oxygen therapy, and the Vojta method. This article provides an overview of salient aspects of popular interventions used in the management of children with cerebral palsy.

Therapeutic monoclonal antibodies for respiratory diseases: Current challenges and perspectives, March 31 - April 1, 2016, Tours, France.

PubMed

Desoubeaux, Guillaume; Reichert, Janice M; Sleeman, Matthew; Reckamp, Karen L; Ryffel, Bernhard; Adamczewski, Jörg P; Sweeney, Theresa D; Vanbever, Rita; Diot, Patrice; Owen, Caroline A; Page, Clive; Lerondel, Stéphanie; Le Pape, Alain; Heuze-Vourc'h, Nathalie

2016-01-01

Monoclonal antibody (mAb) therapeutics have tremendous potential to benefit patients with lung diseases, for which there remains substantial unmet medical need. To capture the current state of mAb research and development in the area of respiratory diseases, the Research Center of Respiratory Diseases (CEPR-INSERM U1100), the Laboratory of Excellence "MAbImprove," the GDR 3260 "Antibodies and therapeutic targeting," and the Grant Research program ARD2020 "Biotherapeutics" invited speakers from industry, academic and government organizations to present their recent research results at the Therapeutic Monoclonal Antibodies for Respiratory Diseases: Current challenges and perspectives congress held March 31 - April 1, 2016 in Tours, France.

Targeting Beta-Amyloid at the CSF: A New Therapeutic Strategy in Alzheimer's Disease.

PubMed

Menendez-Gonzalez, Manuel; Padilla-Zambrano, Huber S; Alvarez, Gabriel; Capetillo-Zarate, Estibaliz; Tomas-Zapico, Cristina; Costa, Agustin

2018-01-01

Although immunotherapies against the amyloid-β (Aβ) peptide tried so date failed to prove sufficient clinical benefit, Aβ still remains the main target in Alzheimer's disease (AD). This article aims to show the rationale of a new therapeutic strategy: clearing Aβ from the CSF continuously (the "CSF-sink" therapeutic strategy). First, we describe the physiologic mechanisms of Aβ clearance and the resulting AD pathology when these mechanisms are altered. Then, we review the experiences with peripheral Aβ-immunotherapy and discuss the related hypothesis of the mechanism of action of "peripheral sink." We also present Aβ-immunotherapies acting on the CNS directly. Finally, we introduce alternative methods of removing Aβ including the "CSF-sink" therapeutic strategy. As soluble peptides are in constant equilibrium between the ISF and the CSF, altering the levels of Aβ oligomers in the CSF would also alter the levels of such proteins in the brain parenchyma. We conclude that interventions based in a "CSF-sink" of Aβ will probably produce a steady clearance of Aβ in the ISF and therefore it may represent a new therapeutic strategy in AD.

Combined oral contraceptives: health benefits beyond contraception.

PubMed

Caserta, D; Ralli, E; Matteucci, E; Bordi, G; Mallozzi, M; Moscarini, M

2014-09-01

It has been recognized for over 50 years that combined oral contraceptives (COCs) are also capable of offering health benefits beyond contraception through the treatment and prevention of several gynaecological and medical disorders. During the last years a constant attention was given to the adverse effects of COCs, whereas their non-contraceptive benefits were underestimated. To date, most women are still unaware of the therapeutic uses of hormonal contraceptives, while on the contrary there is an extensive and constantly increasing of these non-contraceptive health benefits. This review summarizes the conditions of special interest for physicians, including dysmenorrhoea, menorrhagia, hyperandrogenism (acne, hirsutism, polycystic ovary syndrome), functional ovarian cysts, endometriosis, premenstrual syndrome, myomas, pelvic inflammatory disease, bone mineral density, benign breast disease and endometrial/ovarian and colorectal cancer. The benefits of COCs in rheumatoid arthritis, multiple sclerosis, menstrual migraine and in perimenopause have also been treated for more comprehensive information. Using COCs specifically for non-contraceptive indications is still outside the product licence in the majority of cases. We strongly believe that these aspects are not of minor relevance and they deserve a special consideration by health providers and by the mass media, which have the main responsibility in the diffusion of scientific information. Thus, counseling and education are necessary to help women make well-informed health-care decisions and it is also crucial to increase awareness among general practitioners and gynaecologists.

Gratitude and well being: the benefits of appreciation.

PubMed

Sansone, Randy A; Sansone, Lori A

2010-11-01

The word "gratitude" has a number of different meanings, depending on the context. However, a practical clinical definition is as follows-gratitude is the appreciation of what is valuable and meaningful to oneself; it is a general state of thankfulness and/or appreciation. The majority of empirical studies indicate that there is an association between gratitude and a sense of overall well being. However, there are several studies that indicate potential nuances in the relationship between gratitude and well being as well as studies with negative findings. In terms of assessing gratitude, numerous assessment measures are available. From a clinical perspective, there are suggested therapeutic exercises and techniques to enhance gratitude, and they appear relatively simple and easy to integrate into psychotherapy practice. However, the therapeutic efficacy of these techniques remains largely unknown. Only future research will clarify the many questions around assessment, potential benefits, and enhancement of gratitude.

Therapeutic Uses of Triphala in Ayurvedic Medicine

PubMed Central

Denniston, Kate; Chopra, Deepak

2017-01-01

Abstract Aim: The aim of this article is to review the current literature on the therapeutic uses and efficacy of Triphala. Herbal remedies are among the most ancient medicines used in traditional systems of healthcare such as Ayurveda. Triphala, a well-recognized and highly efficacious polyherbal Ayurvedic medicine consisting of fruits of the plant species Emblica officinalis (Amalaki), Terminalia bellerica (Bibhitaki), and Terminalia chebula (Haritaki), is a cornerstone of gastrointestinal and rejuvenative treatment. Methods: A search of the PubMed database was conducted. Results: In addition, numerous additional therapeutic uses described both in the Ayurvedic medical literature and anecdotally are being validated scientifically. In addition to laxative action, Triphala research has found the formula to be potentially effective for several clinical uses such as appetite stimulation, reduction of hyperacidity, antioxidant, anti-inflammatory, immunomodulating, antibacterial, antimutagenic, adaptogenic, hypoglycemic, antineoplastic, chemoprotective, and radioprotective effects, and prevention of dental caries. Polyphenols in Triphala modulate the human gut microbiome and thereby promote the growth of beneficial Bifidobacteria and Lactobacillus while inhibiting the growth of undesirable gut microbes. The bioactivity of Triphala is elicited by gut microbiota to generate a variety of anti-inflammatory compounds. Conclusions: This review summarizes recent data on pharmacological properties and clinical effects of Triphala while highlighting areas in need of additional investigation and clinical development. PMID:28696777

Leaving patients to their own devices? Smart technology, safety and therapeutic relationships.

PubMed

Ho, Anita; Quick, Oliver

2018-03-06

This debate article explores how smart technologies may create a double-edged sword for patient safety and effective therapeutic relationships. Increasing utilization of health monitoring devices by patients will likely become an important aspect of self-care and preventive medicine. It may also help to enhance accurate symptom reports, diagnoses, and prompt referral to specialist care where appropriate. However, the development, marketing, and use of such technology raise significant ethical implications for therapeutic relationships and patient safety. Drawing on lessons learned from other direct-to-consumer health products such as genetic testing, this article explores how smart technology can also pose regulatory challenges and encourage overutilization of healthcare services. In order for smart technology to promote safer care and effective therapeutic encounters, the technology and its utilization must be safe. This article argues for unified regulatory guidelines and better education for both healthcare providers and patients regarding the benefits and risks of these devices.

The Molecular Revolution in Cutaneous Biology: Emerging Landscape in Genomic Dermatology: New Mechanistic Ideas, Gene Editing, and Therapeutic Breakthroughs.

PubMed

Titeux, Matthias; Izmiryan, Araksya; Hovnanian, Alain

2017-05-01

Stunning technological advances in genomics have led to spectacular breakthroughs in the understanding of the underlying defects, biological pathways and therapeutic targets of skin diseases leading to new therapeutic interventions. Next-generation sequencing has revolutionized the identification of disease-causing genes and has a profound impact in deciphering gene and protein signatures in rare and frequent skin diseases. Gene addition strategies have shown efficacy in junctional EB and in recessive dystrophic EB (RDEB). TALENs and Cripsr/Cas9 have emerged as highly efficient new tools to edit genomic sequences to creat new models and to correct or disrupt mutated genes to treat human diseases. Therapeutic approaches have not been limited to DNA modification and strategies at the mRNA, protein and cellular levels have also emerged, some of which have already proven clinical efficacy in RDEB. Improved understanding of the pathogenesis of skin disorders has led to the development of specific drugs or repurposing of existing medicines as in basal cell nevus syndrome, alopecia areata, melanoma and EB simplex. These discoveries pave the way for improved targeted personalized medicine for rare and frequent diseases. It is likely that a growing number of orphan skin diseases will benefit from combinatory new therapies in a near future. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

A therapeutic skating intervention for children with autism spectrum disorder.

PubMed

Casey, Amanda Faith; Quenneville-Himbeault, Gabriel; Normore, Alexa; Davis, Hanna; Martell, Stephen G

2015-01-01

The purpose of this study was to evaluate the effects of a highly structured therapeutic skating intervention on motor outcomes and functional capacity in 2 boys with autism spectrum disorder aged 7 and 10 years. This multiple-baseline, single-subject study assigned participants to three 1-hour skating sessions per week for 12 weeks focusing on skill and motor development. Multiple data points assessed (a) fidelity to the intervention and (b) outcomes measures including the Pediatric Balance Scale, Timed Up and Go, floor to stand, Six-Minute Walk Test, goal attainment, and weekly on-ice testing. Improvements were found in balance, motor behavior, and functional capacity by posttest with gains remaining above pretest levels at follow-up. Therapeutic skating may produce physical benefits for children with autism spectrum disorder and offer a viable, inexpensive community-based alternative to other forms of physical activity.

Therapeutic benefit of balneotherapy and hydrotherapy in the management of fibromyalgia syndrome: a qualitative systematic review and meta-analysis of randomized controlled trials.

PubMed

Naumann, Johannes; Sadaghiani, Catharina

2014-07-07

In the present systematic review and meta-analysis, we assessed the effectiveness of different forms of balneotherapy (BT) and hydrotherapy (HT) in the management of fibromyalgia syndrome (FMS). A systematic literature search was conducted through April 2013 (Medline via Pubmed, Cochrane Central Register of Controlled Trials, EMBASE, and CAMBASE). Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Meta-analysis showed moderate-to-strong evidence for a small reduction in pain (SMD -0.42; 95% CI [-0.61, -0.24]; P < 0.00001; I2 = 0%) with regard to HT (8 studies, 462 participants; 3 low-risk studies, 223 participants), and moderate-to-strong evidence for a small improvement in health-related quality of life (HRQOL; 7 studies, 398 participants; 3 low-risk studies, 223 participants) at the end of treatment (SMD -0.40; 95% CI [-0.62, -0.18]; P = 0.0004; I2 = 15%). No effect was seen at the end of treatment for depressive symptoms and tender point count (TPC). High-quality studies with larger sample sizes are needed to confirm the therapeutic benefit of BT and HT, with focus on long-term results and maintenance of the beneficial effects.

What is the evidence to support the use of therapeutic gardens for the elderly?

PubMed

Detweiler, Mark B; Sharma, Taral; Detweiler, Jonna G; Murphy, Pamela F; Lane, Sandra; Carman, Jack; Chudhary, Amara S; Halling, Mary H; Kim, Kye Y

2012-06-01

Horticulture therapy employs plants and gardening activities in therapeutic and rehabilitation activities and could be utilized to improve the quality of life of the worldwide aging population, possibly reducing costs for long-term, assisted living and dementia unit residents. Preliminary studies have reported the benefits of horticultural therapy and garden settings in reduction of pain, improvement in attention, lessening of stress, modulation of agitation, lowering of as needed medications, antipsychotics and reduction of falls. This is especially relevant for both the United States and the Republic of Korea since aging is occurring at an unprecedented rate, with Korea experiencing some of the world's greatest increases in elderly populations. In support of the role of nature as a therapeutic modality in geriatrics, most of the existing studies of garden settings have utilized views of nature or indoor plants with sparse studies employing therapeutic gardens and rehabilitation greenhouses. With few controlled clinical trials demonstrating the positive or negative effects of the use of garden settings for the rehabilitation of the aging populations, a more vigorous quantitative analysis of the benefits is long overdue. This literature review presents the data supporting future studies of the effects of natural settings for the long term care and rehabilitation of the elderly having the medical and mental health problems frequently occurring with aging.

What Is the Evidence to Support the Use of Therapeutic Gardens for the Elderly?

PubMed Central

Detweiler, Mark B.; Sharma, Taral; Detweiler, Jonna G.; Murphy, Pamela F.; Lane, Sandra; Carman, Jack; Chudhary, Amara S.; Halling, Mary H.

2012-01-01

Horticulture therapy employs plants and gardening activities in therapeutic and rehabilitation activities and could be utilized to improve the quality of life of the worldwide aging population, possibly reducing costs for long-term, assisted living and dementia unit residents. Preliminary studies have reported the benefits of horticultural therapy and garden settings in reduction of pain, improvement in attention, lessening of stress, modulation of agitation, lowering of as needed medications, antipsychotics and reduction of falls. This is especially relevant for both the United States and the Republic of Korea since aging is occurring at an unprecedented rate, with Korea experiencing some of the world's greatest increases in elderly populations. In support of the role of nature as a therapeutic modality in geriatrics, most of the existing studies of garden settings have utilized views of nature or indoor plants with sparse studies employing therapeutic gardens and rehabilitation greenhouses. With few controlled clinical trials demonstrating the positive or negative effects of the use of garden settings for the rehabilitation of the aging populations, a more vigorous quantitative analysis of the benefits is long overdue. This literature review presents the data supporting future studies of the effects of natural settings for the long term care and rehabilitation of the elderly having the medical and mental health problems frequently occurring with aging. PMID:22707959

Benefiting from 'evil': an incipient moral problem in human stem cell research.

PubMed

Green, Ronald M

2002-11-01

When does benefiting from others' wrongdoing effectively make one a moral accomplice in their evil deeds? If stem cell research lives up to its therapeutic promise, this question (which has previously cropped up in debates over fetal tissue research or the use of Nazi research data) is likely to become a central one for opponents of embryo destruction. I argue that benefiting from wrongdoing is prima facie morally wrong under any of three conditions: (1) when the wrongdoing is one's agent; (2) when acceptance of benefit directly encourages the repetition of the wrongful deed (even though no agency relationship is involved); and (3) when acceptance of a benefit legitimates a wrongful practice. I conclude by showing that, because of the ways in which most embryonic stem cell lines come into being, people who oppose embryo destruction may use human embryonic stem cells without incurring moral blame.

Therapeutic plasma exchange: a technical and operational review.

PubMed

Kaplan, Andre A

2013-02-01

Therapeutic plasma exchange (TPE) is an extracorporeal blood purification technique designed for the removal of large molecular weight substances. Examples of these substances include pathogenic autoantibodies, immune complexes, cryoglobulins, myeloma light chains, endotoxin and cholesterol containing lipoproteins. The basic premise of the treatment is that removal of these substances will allow for the reversal of the pathologic processes related to their presence. This review will cover the techniques for performing TPE, the kinetics of the removal of large molecules from the plasma and the benefits and risks of the different types of replacement fluids. Copyright © 2013 Wiley Periodicals, Inc.

Walking groups for women with breast cancer: Mobilising therapeutic assemblages of walk, talk and place.

PubMed

Ireland, Aileen V; Finnegan-John, Jennifer; Hubbard, Gill; Scanlon, Karen; Kyle, Richard G

2018-03-08

Walking is widely accepted as a safe and effective method of promoting rehabilitation and a return to physical activity after a cancer diagnosis. Little research has considered the therapeutic qualities of landscape in relation to understanding women's recovery from breast cancer, and no study has considered the supportive and therapeutic benefits that walking groups might contribute to their wellbeing. Through a study of a volunteer-led walking group intervention for women living with and beyond breast cancer (Best Foot Forward) we address this gap. A mixed-methods design was used including questionnaires with walkers (n = 35) and walk leaders (n = 13); telephone interviews with walkers (n = 4) and walk leaders (n = 9); and walking interviews conducted outdoors and on the move with walkers (n = 15) and walk leaders (n = 4). Questionnaires were analysed descriptively. Interviews were audio-recorded, transcribed verbatim, and analysed thematically. Our study found that the combination of walking and talking enabled conversations to roam freely between topics and individuals, encouraging everyday and cancer-related conversation that created a form of 'shoulder-to-shoulder support' that might not occur in sedentary supportive care settings. Walking interviews pointed to three facets of the outdoor landscape - as un/natural, dis/placed and im/mobile - that walkers felt imbued it with therapeutic qualities. 'Shoulder-to-shoulder support' was therefore found to be contingent on the therapeutic assemblage of place, walk and talk. Thus, beyond the physical benefits that walking brings, it is the complex assemblage of walking and talking in combination with the fluid navigation between multiple spaces that mobilises a therapeutic assemblage that promotes wellbeing in people living with and beyond breast cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Benefits of Meditation for Outdoor Education.

ERIC Educational Resources Information Center

Ettenger, Jim

Outdoor education is not merely about learning outdoor skills; it should also involve self-reflective activities. Meditation is a technique used for self-reflection, has many proven psychological and physiological benefits, and would be a good addition to any wilderness program. Research has shown that the psychological benefits of meditation…

Therapeutic potential of n-3 polyunsaturated fatty acids in disease.

PubMed

Fetterman, James W; Zdanowicz, Martin M

2009-07-01

The potential therapeutic benefits of supplementation with n-3 polyunsaturated fatty acids (PUFAs) in various diseases are reviewed, and the antiinflammatory actions, activity, and potential drug interactions and adverse effects of n-3 PUFAs are discussed. Fish oils are an excellent source of long-chain n-3 PUFAs, such as eicosapentaenoic acid and docosahexaenoic acid. After consumption, n-3 PUFAs can be incorporated into cell membranes and reduce the amount of arachidonic acid available for the synthesis of proinflammatory eicosanoids (e.g., prostaglandins, leukotrienes). Likewise, n-3 PUFAs can also reduce the production of inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-1, and interleukin-6. Considerable research has been conducted to evaluate the potential therapeutic effects of fish oils in numerous conditions, including arthritis, coronary artery disease, inflammatory bowel disease, asthma, and sepsis, all of which have inflammation as a key component of their pathology. Additional investigations into the use of supplementation with fish oils in patients with neural injury, cancer, ocular diseases, and critical illness have recently been conducted. The most commonly reported adverse effects of fish oil supplements are a fishy aftertaste and gastrointestinal upset. When recommending an n-3 PUFA, clinicians should be aware of any possible adverse effect or drug interaction that, although not necessarily clinically significant, may occur, especially for patients who may be susceptible to increased bleeding (e.g., patients taking warfarin). The n-3 PUFAs have been shown to be efficacious in treating and preventing various diseases. The wide variation in dosages and formulations used in studies makes it difficult to recommend dosages for specific treatment goals.

Benefit of the addition of hormone therapy to neoadjuvant anthracycline-based chemotherapy for breast cancer: comparison of predicted and observed pCR.

PubMed

Generali, Daniele; Corona, Silvia Paola; Pusztai, Lajos; Rouzier, Roman; Allevi, Giovanni; Aguggini, Sergio; Milani, Manuela; Strina, Carla; Frati, Albane

2018-03-01

Neoadjuvant hormonal therapy is generally considered a valid option for hormone receptor positive breast cancer (BC) patients who are unfit for chemotherapy or surgery. Whilst numerous studies analyzed efficacy of neoadjuvant chemotherapy (CT) or endocrine therapy (HT) alone in hormone receptor positive patients, there is a lack of research looking at the usefulness of a preoperative combinatorial approach of CT and HT in this patient subgroup. Using a predictive model previously described in the literature, developed to analyze the probability of benefit from preoperative chemotherapy, we were able to compare pathological complete response (pCR) rates expected with the use of CT alone with the pCR rates reported in a population of 192 patients treated with the combination of tamoxifen plus anthracycline-based CT at Cremona Hospital between 2003 and 2006. Even with a relatively small patient population, this approach provided insightful information for the selection of hormone receptor positive BC patients most likely to benefit from the use of preoperative HT and CT in combination. Whilst no statistically significant benefit was obtained with the addition of tamoxifen to neoadjuvant chemotherapy in the entire population, or in any of the molecular stratification subgroups, the analysis of the calibration curve showed that a combinatorial approach may improve pCR in patients with luminal B tumors. More specific trials should be designed to confirm our initial results. To the best of our knowledge, this is the first report investigating the efficacy of the combination of CT and HT in the neoadjuvant treatment of hormone receptor positive BC.

The social dimensions of therapeutic horticulture.

PubMed

Harris, Holly

2017-07-01

Harnessing nature to promote mental health is increasingly seen as a sustainable solution to healthcare across the industrialised world. The benefits of these approaches to well-being include reduced symptoms of anxiety, depression and improved social functioning. Many studies assume that contact with nature is the main therapeutic component of these interventions yet 'green care' programmes typically include activities not based on 'nature' that may contribute to positive outcomes. This study explored the views of service users participating in a Therapeutic Horticultural programme on what factors promoted their engagement in the project, to identify variables other than 'nature' that may be responsible for successful engagement in these programmes. A secondary aim was to assess the significance 'nature' plays including, for example whether a prior interest in horticultural-related activities, such as gardening, is significant. Two focus groups were held with mental health service users (n = 15) attending a gardening project in south-east England. Findings revealed that the social element of the project was the key facilitator to engagement; the flexible structure of the gardening project was also significant and allowed service users to feel empowered. 'Nature' evoked a sense of calm and provided participants with a non-threatening space that was engaging. © 2017 John Wiley & Sons Ltd.

Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke.

PubMed

Hayakawa, Kazuhide; Mishima, Kenichi; Fujiwara, Michihiro

2010-07-08

Cannabis contains the psychoactive component delta⁸-tetrahydrocannabinol (delta⁸-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol. It is well-known that delta⁸-THC and other cannabinoid CB₁ receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta⁸-THC also mediates psychological effects through the activation of the CB₁ receptor in the central nervous system. In addition to the CB₁ receptor agonists, cannabis also contains therapeutically active components which are CB₁ receptor independent. Of the CB₁ receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson's disease, Alzheimer's disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB₁ receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.

Therapeutic robotics for children with disabilities: a case study.

PubMed

Drane, James; Safos, Charlotte; Lathan, Corinna E

2009-01-01

The advancement of technology is having a profound effect on enhancing the lives of children with disabilities. As advances in biomedical technology allow research breakthroughs to continue at a steady pace, more and more is being discovered about the nature of different disorders in children. At the same time, partly due to the continuing rapid rate of advancement (and societal acceptance) of robotics technology, researchers, educators, and therapists are exploring the idea that robots might be used as an effective therapeutic and educational tool. Over the past nine years, AnthroTronix has collaborated extensively with therapists, educators, researchers, parents, and children to uncover the therapeutic and educational benefits of including robotics as part of rehabilitation curriculum for children. As a central part of this effort, the company has worked with its colleagues to develop and refine the CosmoBot system, an interactive robotic toolkit designed to enhance therapy, education, and play for children with disabilities.

Therapeutic communication training in long-term care institutions: recommendations for future research.

PubMed

Levy-Storms, Lené

2008-10-01

The purpose of this review is to critique contemporary experimental research and to recommend future directions for research interventions on nursing aides' therapeutic communication with older adults who have cognitive impairment and/or dementia in institutional long-term care settings. This literature review covers 13 journal articles (1999-2006) and focuses on the strengths and weaknesses of experimental research interventions to improve nursing aides' therapeutic communication with older adults who have cognitive impairment and/or dementia in long-term care settings. Based on this review, recommendations for improved experimental designs include a minimum of two groups with one being a control and randomization of subjects at the care unit level, an average 3-5h of total training, a minimum of a 6-month total evaluation period, and objective outcomes relevant to both nursing aides and residents. Findings from studies in this review indicate that the following therapeutic communication techniques can be taught and can benefit staffs and older adults' quality of life: verbal and non-verbal communication behaviors including open-ended questions, positive statements, eye contact, affective touch, and smiling. Some evidence exists to support that nursing aides can improve their therapeutic communication during care. Nursing aides need not only more training in therapeutic communication but also ongoing, dedicated supervision in psychosocial aspects of care.

Delivery of Therapeutic Proteins via Extracellular Vesicles: Review and Potential Treatments for Parkinson's Disease, Glioma, and Schwannoma.

PubMed

Hall, Justin; Prabhakar, Shilpa; Balaj, Leonora; Lai, Charles P; Cerione, Richard A; Breakefield, Xandra O

2016-04-01

Extracellular vesicles present an attractive delivery vehicle for therapeutic proteins. They intrinsically contain many proteins which can provide information to other cells. Advantages include reduced immune reactivity, especially if derived from the same host, stability in biologic fluids, and ability to target uptake. Those from mesenchymal stem cells appear to be intrinsically therapeutic, while those from cancer cells promote tumor progression. Therapeutic proteins can be loaded into vesicles by overexpression in the donor cell, with oligomerization and membrane sequences increasing their loading. Examples of protein delivery for therapeutic benefit in pre-clinical models include delivery of: catalase for Parkinson's disease to reduce oxidative stress and thus help neurons to survive; prodrug activating enzymes which can convert a prodrug which crosses the blood-brain barrier into a toxic chemotherapeutic drug for schwannomas and gliomas; and the apoptosis-inducing enzyme, caspase-1 under a Schwann cell specific promoter for schwannoma. This therapeutic delivery strategy is novel and being explored for a number of diseases.

Evaluation of Two Dry Commercial Therapeutic Diets for the Management of Feline Chronic Gastroenteropathy

PubMed Central

Perea, Sally C.; Marks, Stanley L.; Daristotle, Leighann; Koochaki, Patricia E.; Haydock, Richard

2017-01-01

effective in the management of feline chronic vomiting. Cats that fail to respond to this dietary approach after a 2- to 4-week trial may benefit from a limited novel or hydrolyzed ingredient formula and may require additional diagnostics to better characterize the underlying disease. PMID:28540291

The possible therapeutic benefits of utilizing motion gaming systems on pediatric patients presenting autism.

PubMed

Crowder, Stephen A; Merritte, Kristin

2013-09-01

Autism is a pervasive developmental disorder that affects a growing number of children in the United States each year. It is characterized by substantive differences in brain structure and function that lead to long-term cognitive and social deficits. These differences, combined with the increasing prevalence of autism in children, warrant the need for development of innovative, cost-effective and widely available alternative and complementary therapies. Motion gaming has the potential to be highly efficacious as a therapeutic technique to aid in developing memory, facial recognition, motor skills and social integration in the pediatric autistic population. This paper outlines the major deficits in the brains of individuals with autism and describes how the use of motion gaming could capitalize on the individual strengths of each patient, leading to improvements in a variety of deficits.

Toward a new generation of therapeutics: artificial cell targeted delivery of live cells for therapy.

PubMed

Prakash, Satya; Martoni, Christopher

2006-01-01

Scientific evidence in the prevention and treatment of various disorders is accumulating regarding probiotics. The health benefits supported by adequate clinical data include increased resistance to infectious disease, decreased duration of diarrhea, management of inflammatory bowel disease, reduction of serum cholesterol, prevention of allergy, modulation of cytokine gene expression, and suppression of carcinogen production. Recent ventures in metabolic engineering and heterologous protein expression have enhanced the enzymatic and immunomodulatory effects of probiotics and, with time, may allow more active intervention among critical care patients. In addition, a number of approaches are currently being explored, including the physical and chemical protection of cells, to increase probiotic viability and its health benefits. Traditional immobilization of probiotics in gel matrices, most notably calcium alginate and kappa-carrageenan, has frequently been employed, with noted improvements in viability during freezing and storage. Conflicting reports exist, however, on the protection offered by immobilization from harsh physiologic environments. An alternative approach, microencapsulation in "artificial cells," builds on immobilization technologies by combining enhanced mechanical stability of the capsule membrane with improved mass transport, increased cell loading, and greater control of parameters. This review summarizes the current clinical status of probiotics, examines the promises and challenges of current immobilization technologies, and presents the concept of artificial cells for effective delivery of therapeutic bacterial cells.

What are true community benefits?

PubMed

Trocchio, J

1996-01-01

Not-for-profit healthcare organizations have increasingly recognized the need to document their community benefit services, but not all healthcare services should be included in a community benefits report. Some services are reasonably expected of any high-quality healthcare organization, regardless of its tax status. Others are provided as part of a commitment to the community, but they cannot or should not be quantified. A third group of services, however, can be counted and reported in an inventory of benefits. To qualify as a true community benefit, an activity must respond to a particular health problem in the community, especially one involving special populations. In addition, it must be financed through philanthropic contributions, volunteer efforts, or an endowment; generate a low or negative margin; or be a service that would be discontinued if the decision were made on a purely financial basis. Once an organization has determined that an activity is a community benefit and not a basic service or promotional program, organizational leaders must decide whether to include the service in a quantitative inventory or in a more general narrative without assignment of specific financial benefit. The community benefit services might be further broken down according to the intended recipient, whether it is the poor or the broader community.

20 CFR 416.263 - No additional application needed.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false No additional application needed. 416.263 Section 416.263 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Eligibility Special Provisions for People Who Work Despite A Disabling...

20 CFR 416.263 - No additional application needed.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false No additional application needed. 416.263 Section 416.263 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Eligibility Special Provisions for People Who Work Despite A Disabling...

20 CFR 416.263 - No additional application needed.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false No additional application needed. 416.263 Section 416.263 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Eligibility Special Provisions for People Who Work Despite A Disabling...

20 CFR 416.263 - No additional application needed.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false No additional application needed. 416.263 Section 416.263 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Eligibility Special Provisions for People Who Work Despite A Disabling...

Determinants of immunogenic response to protein therapeutics.

PubMed

Singh, Satish K; Cousens, Leslie P; Alvarez, David; Mahajan, Pramod B

2012-09-01

Protein therapeutics occupy a very significant position in the biopharmaceutical market. In addition to the preclinical, clinical and post marketing challenges common to other drugs, unwanted immunogenicity is known to affect efficacy and/or safety of most biotherapeutics. A standard set of immunogenicity risk factors are routinely used to inform monitoring strategies in clinical studies. A number of in-silico, in vivo and in vitro approaches have also been employed to predict immunogenicity of biotherapeutics, but with limited success. Emerging data also indicates the role of immune tolerance mechanisms and impact of several product-related factors on modulating host immune responses. Thus, a comprehensive discussion of the impact of innate and adaptive mechanisms and molecules involved in induction of host immune responses on immunogenicity of protein therapeutics is needed. A detailed understanding of these issues is essential in order to fully exploit the therapeutic potential of this class of drugs. This Roundtable Session was designed to provide a common platform for discussing basic immunobiological and pharmacological issues related to the role of biotherapeutic-associated risk factors, as well as host immune system in immunogenicity against protein therapeutics. The session included overview presentations from three speakers, followed by a panel discussion with audience participation. Copyright © 2012. Published by Elsevier Ltd.. All rights reserved.

Pitfalls associated with the therapeutic reference pricing practice of asthma medication

PubMed Central

2012-01-01

Background Therapeutic reference pricing (TRP) based on the WHO daily defined dose (DDD) is a method frequently employed for the cost-containment of pharmaceuticals. Our objective was to compare average drug use in the real world with DDD and to evaluate whether TRP based on DDD could result in cost savings on maintenance medication and the total direct health expenditures for asthma patients treated with Symbicort Turbuhaler (SYT) and Seretide Diskus (SED) in Hungary. Methods Real-world data were derived from the Hungarian National Health Insurance Fund database. Average doses and costs were compared between the high-dose and medium-dose SYT and SED groups. Multiple linear regressions were employed to adjust the data for differences in the gender and age distribution of patients. Results 27,779 patients with asthma were included in the analysis. Average drug use was lower than DDD in all groups, 1.38-1.95 inhalations in both SED groups, 1.28-1.97 and 1.74-2.49 inhalations in the medium and high-dose SYT groups, respectively. Although the cost of SED based on the DDD would be much lower than the cost of SYT in the medium-dose groups, no difference was found in the actual cost of the maintenance therapy. No significant differences were found between the groups in terms of total medical costs. Conclusions Cost-containment initiatives by payers may influence clinical decisions. TRP for inhalation asthma drugs raises special concern, because of differences in the therapeutic profile of pharmaceuticals and the lack of proven financial benefits after exclusion of the effect of generic price erosion. Our findings indicate that the presented TRP approach of asthma medications based on the daily therapeutic costs according to the WHO DDD does not result in reduced public healthcare spending in Hungary. Further analysis is required to show whether TRP generates additional expenditures by inducing switching costs and reducing patient compliance. Potential confounding factors

Pitfalls associated with the therapeutic reference pricing practice of asthma medication.

PubMed

Kalo, Zoltan; Abonyi-Toth, Zsolt; Bartfai, Zoltan; Voko, Zoltan

2012-07-20

Therapeutic reference pricing (TRP) based on the WHO daily defined dose (DDD) is a method frequently employed for the cost-containment of pharmaceuticals. Our objective was to compare average drug use in the real world with DDD and to evaluate whether TRP based on DDD could result in cost savings on maintenance medication and the total direct health expenditures for asthma patients treated with Symbicort Turbuhaler (SYT) and Seretide Diskus (SED) in Hungary. Real-world data were derived from the Hungarian National Health Insurance Fund database. Average doses and costs were compared between the high-dose and medium-dose SYT and SED groups. Multiple linear regressions were employed to adjust the data for differences in the gender and age distribution of patients. 27,779 patients with asthma were included in the analysis. Average drug use was lower than DDD in all groups, 1.38-1.95 inhalations in both SED groups, 1.28-1.97 and 1.74-2.49 inhalations in the medium and high-dose SYT groups, respectively. Although the cost of SED based on the DDD would be much lower than the cost of SYT in the medium-dose groups, no difference was found in the actual cost of the maintenance therapy. No significant differences were found between the groups in terms of total medical costs. Cost-containment initiatives by payers may influence clinical decisions. TRP for inhalation asthma drugs raises special concern, because of differences in the therapeutic profile of pharmaceuticals and the lack of proven financial benefits after exclusion of the effect of generic price erosion. Our findings indicate that the presented TRP approach of asthma medications based on the daily therapeutic costs according to the WHO DDD does not result in reduced public healthcare spending in Hungary. Further analysis is required to show whether TRP generates additional expenditures by inducing switching costs and reducing patient compliance. Potential confounding factors may limit the generalisability of our

29 CFR 4022.23 - Computation of maximum guaranteeable benefits.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Converting Temporary Additional Benefit Under Step-Down Life Annuity Age of participant 1 at the later of the... benefit payable for life commencing at age 65, the maximum guaranteeable monthly amount of such benefit... age 65 that corresponds to the later of the participant's age at the termination date or his age at...

Recent Progress in Functional Micellar Carriers with Intrinsic Therapeutic Activities for Anticancer Drug Delivery.

PubMed

Qu, Ying; Chu, BingYang; Shi, Kun; Peng, JinRong; Qian, ZhiYong

2017-12-01

Polymeric micelles have presented superior delivery properties for poorly water-soluble chemotherapeutic agents. However, it remains discouraging that there may be some additional short or long-term toxicities caused by the metabolites of high quantities of carriers. If carriers had simultaneous therapeutic effects with the drug, these issues would not be a concern. For this, carriers not only simply act as drug carriers, but also exert an intrinsic therapeutic effect as a therapeutic agent. The functional micellar carriers would be beneficial to maximize the anticancer effect, overcome the drug resistance and reduce the systemic toxicity. In this review, we aim to summarize the recent progress on the development of functional micellar carriers with intrinsic anticancer activities for the delivery of anticancer drugs. This review focuses on the design strategies, properties of carriers and the drug loading behavior. In addition, the combinational therapeutic effects between carriers and chemotherapeutic agents are also discussed.

The vascular endothelium in diabetes--a therapeutic target?

PubMed

Mather, Kieren J

2013-03-01

Insulin resistance affects the vascular endothelium, and contributes to systemic insulin resistance by directly impairing the actions of insulin to redistribute blood flow as part of its normal actions driving muscle glucose uptake. Impaired vascular function is a component of the insulin resistance syndrome, and is a feature of type 2 diabetes. On this basis, the vascular endothelium has emerged as a therapeutic target where the intent is to improve systemic metabolic state by improving vascular function. We review the available literature presenting studies in humans, evaluating the effects of metabolically targeted and vascular targeted therapies on insulin action and systemic metabolism. Therapies that improve systemic insulin resistance exert strong concurrent effects to improve vascular function and vascular insulin action. RAS-acting agents and statins have widely recognized beneficial effects on vascular function but have not uniformly produced the hoped-for metabolic benefits. These observations support the notion that systemic metabolic benefits can arise from therapies targeted at the endothelium, but improving vascular insulin action does not result from all treatments that improve endothelium-dependent vasodilation. A better understanding of the mechanisms of insulin's actions in the vascular wall will advance our understanding of the specificity of these responses, and allow us to better target the vasculature for metabolic benefits.

Survival benefit with proapoptotic molecular and pathologic responses from dual targeting of mammalian target of rapamycin and epidermal growth factor receptor in a preclinical model of pancreatic neuroendocrine carcinogenesis.

PubMed

Chiu, Christopher W; Nozawa, Hiroaki; Hanahan, Douglas

2010-10-10

Pancreatic neuroendocrine tumors (PNETs), although rare, often metastasize, such that surgery, the only potentially curative therapy, is not possible. There is no effective systemic therapy for patients with advanced PNETs. Therefore, new strategies are needed. Toward that end, we investigated the potential benefit of dual therapeutic targeting of the epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) kinases, using a preclinical mouse model of PNET. Rapamycin and erlotinib, inhibitors of mTOR and EGFR, respectively, were used to treat RIP-Tag2 transgenic mice bearing advanced multifocal PNET. Tumor growth and survival were monitored, and tumors were surveyed for potential biomarkers of response to the therapeutics. Rapamycin monotherapy was notably efficacious, prolonging survival concomitant with tumor stasis (stable disease). However, the tumors developed resistance, as evidenced by eventual relapse to progressive tumor growth. Erlotinib monotherapy slowed tumor growth and elicited a marginal survival benefit. In combination, there was an unprecedented survival benefit in the face of this aggressive multifocal cancer and, in contrast to either monotherapy, the development of adaptive resistance was not apparent. Additionally, the antiapoptotic protein survivin was implicated as a biomarker of sensitivity and beneficial responses to the dual targeted therapy. Preclinical trials in a mouse model of endogenous PNET suggest that combined targeting of the mTOR and EGFR signaling pathways could have potential clinical benefit in treating PNET. These results have encouraged development of an ongoing phase II clinical trial aimed to evaluate the efficacy of this treatment regimen in human neuroendocrine tumors.

Therapeutic gold, silver, and platinum nanoparticles.

PubMed

Yamada, Miko; Foote, Matthew; Prow, Tarl W

2015-01-01

There are an abundance of nanoparticle technologies being developed for use as part of therapeutic strategies. This review focuses on a narrow class of metal nanoparticles that have therapeutic potential that is a consequence of elemental composition and size. The most widely known of these are gold nanoshells that have been developed over the last two decades for photothermal ablation in superficial cancers. The therapeutic effect is the outcome of the thickness and diameter of the gold shell that enables fine tuning of the plasmon resonance. When these metal nanoparticles are exposed to the relevant wavelength of light, their temperature rapidly increases. This in turn induces a localized photothermal ablation that kills the surrounding tumor tissue. Similarly, gold nanoparticles have been developed to enhance radiotherapy. The high-Z nature of gold dramatically increases the photoelectric cross-section. Thus, the photoelectric effects are significantly increased. The outcome of these interactions is enhanced tumor killing with lower doses of radiation, all while sparing tissue without gold nanoparticles. Silver nanoparticles have been used for their wound healing properties in addition to enhancing the tumor-killing effects of anticancer drugs. Finally, platinum nanoparticles are thought to serve as a reservoir for platinum ions that can induce DNA damage in cancer cells. The future is bright with the path to clinical trials is largely cleared for some of the less complex therapeutic metal nanoparticle systems. © 2014 The Authors. WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals, Inc.

Therapeutic bond judgments: Congruence and incongruence.

PubMed

Atzil-Slonim, Dana; Bar-Kalifa, Eran; Rafaeli, Eshkol; Lutz, Wolfgang; Rubel, Julian; Schiefele, Ann-Kathrin; Peri, Tuvia

2015-08-01

The present study had 2 aims: (a) to implement West and Kenny's (2011) Truth-and-Bias model to simultaneously assess the temporal congruence and directional discrepancy between clients' and therapists' ratings of the bond facet of the therapeutic alliance, as they cofluctuate from session to session; and (b) to examine whether symptom severity and a personality disorder (PD) diagnosis moderate congruence and/or discrepancy. Participants included 213 clients treated by 49 therapists. At pretreatment, clients were assessed for a PD diagnosis and completed symptom measures. Symptom severity was also assessed at the beginning of each session, using client self-reports. Both clients and therapists rated the therapeutic bond at the end of each session. Therapists and clients exhibited substantial temporal congruence in their session-by-session bond ratings, but therapists' ratings tended to be lower than their clients' across sessions. Additionally, therapeutic dyads whose session-by-session ratings were more congruent also tended to have a larger directional discrepancy (clients' ratings being higher). Pretreatment symptom severity and PD diagnosis did not moderate either temporal congruence or discrepancy at the dyad level; however, during sessions when clients were more symptomatic, therapist and client ratings were both farther apart and tracked each other less closely. Our findings are consistent with a "better safe than sorry" pattern, which suggests that therapists are motivated to take a vigilant approach that may lead both to underestimation and to attunement to fluctuations in the therapeutic bond. (c) 2015 APA, all rights reserved).

Design of clinical trials for therapeutic cancer vaccines development.

PubMed

Mackiewicz, Jacek; Mackiewicz, Andrzej

2009-12-25

Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate.

Therapeutic treatment of Marburg and Ravn virus infection in nonhuman primates with a human monoclonal antibody.

PubMed

Mire, Chad E; Geisbert, Joan B; Borisevich, Viktoriya; Fenton, Karla A; Agans, Krystle N; Flyak, Andrew I; Deer, Daniel J; Steinkellner, Herta; Bohorov, Ognian; Bohorova, Natasha; Goodman, Charles; Hiatt, Andrew; Kim, Do H; Pauly, Michael H; Velasco, Jesus; Whaley, Kevin J; Crowe, James E; Zeitlin, Larry; Geisbert, Thomas W

2017-04-05

As observed during the 2013-2016 Ebola virus disease epidemic, containment of filovirus outbreaks is challenging and made more difficult by the lack of approved vaccine or therapeutic options. Marburg and Ravn viruses are highly virulent and cause severe and frequently lethal disease in humans. Monoclonal antibodies (mAbs) are a platform technology in wide use for autoimmune and oncology indications. Previously, we described human mAbs that can protect mice from lethal challenge with Marburg virus. We demonstrate that one of these mAbs, MR191-N, can confer a survival benefit of up to 100% to Marburg or Ravn virus-infected rhesus macaques when treatment is initiated up to 5 days post-inoculation. These findings extend the small but growing body of evidence that mAbs can impart therapeutic benefit during advanced stages of disease with highly virulent viruses and could be useful in epidemic settings. Copyright © 2017, American Association for the Advancement of Science.

Inflammation and therapeutic vaccination in CNS diseases

NASA Astrophysics Data System (ADS)

Weiner, Howard L.; Selkoe, Dennis J.

2002-12-01

The spectrum of inflammatory diseases of the central nervous system has been steadily expanding from classical autoimmune disorders such as multiple sclerosis to far more diverse diseases. Evidence now suggests that syndromes such as Alzheimer's disease and stroke have important inflammatory and immune components and may be amenable to treatment by anti-inflammatory and immunotherapeutic approaches. The notion of 'vaccinating' individuals against a neurodegenerative disorder such as Alzheimer's disease is a marked departure from classical thinking about mechanism and treatment, and yet therapeutic vaccines for both Alzheimer's disease and multiple sclerosis have been validated in animal models and are in the clinic. Such approaches, however, have the potential to induce unwanted inflammatory responses as well as to provide benefit.

Benchmarking DoD Use of Additive Manufacturing and Quantifying Costs

DTIC Science & Technology

2017-03-01

46 VI. Cost Benefit ...developing a cost model. The US Army Logistics Innovation Agency published a study called “Additive Manufacturing Cost - Benefit Analysis”. This...to over fifteen thousand dollars on GSA Advantage. Desktop printers do not require extensive support equipment. 47    VI. Cost Benefit

The benefits of using bluetooth accessories with hearing aids.

PubMed

Smith, Pauline; Davis, Adrian

2014-10-01

To investigate the benefits in reported outcomes after providing bluetooth accessories for established hearing aid users. Prospective observational study using validated quantitative outcome measures and detailed patient narrative before and two months after patients were provided with bluetooth accessories. Twelve patients with bilateral NHS hearing aids participated. They had a wide range of ages and hearing loss. After two months, 10 patients reported substantial additional benefit and kept the accessories; two returned them for various reasons. Statistically significant changes were seen in two validated outcome measures: the Glasgow Hearing Aid Benefit Profile and the International Outcome Inventory - Hearing Aids, but not in the Speech, Spatial and Qualities of Hearing Scale. Two notable benefits were reported: some described hearing the emotion and mood in a voice for the first time; others were amazed to report an improved ability to hear film or to hold conversations over the telephone. The provision of bluetooth accessories can give additional reported benefit for some patients - we need better knowledge about who benefits, and whether further support/training to individuals would make a difference.

Therapeutic recreation treatment time during inpatient rehabilitation

PubMed Central

Gassaway, Julie; Dijkers, Marcel; Rider, Cecelia; Edens, Kelly; Cahow, Claire; Joyce, Joan

2011-01-01

Objective Following spinal cord injury (SCI), certified therapeutic recreation specialists (CTRSs) work with patients during rehabilitation to re-create leisure lifestyles. Although there is much literature available to describe the benefits of recreation, little has been written about the process of inpatient or outpatient rehabilitation therapeutic recreation (TR) programs or the effectiveness of such programs. To delineate how TR time is used during inpatient rehabilitation for SCI. Methods Six rehabilitation centers enrolled 600 patients with traumatic SCI for an observational study. CTRSs documented time spent on each of a set of specific TR activities during each patient encounter. Patterns of time use are described, for all patients and by neurologic category. Ordinary least-squares stepwise regression models are used to identify patient and injury characteristics predictive of total treatment time (overall and average per week) and time spent in TR activities. Results Ninety-four percent of patients enrolled in the SCIRehab study participated in TR. Patients received a mean total of 17.5 hours of TR; significant differences were seen in the amount of time spent in each activity among and within neurologic groups. The majority (76%) of patients participated in at least one structured therapeutic outing. Patient and injury characteristics explained little of the variation in time spent within activities. Conclusion The large amount of variability seen in TR treatment time within and among injury group categories, which is not explained well by patient and injury characteristics, sets the stage for future analyses to associate treatments with outcomes. PMID:21675356

Mineral waters, electricity, and hemlock: devising therapeutics for children in eighteenth-century institutions.

PubMed

Mathisen, Ashley

2013-01-01

The development of paediatric medicine as a formal field of medical specialisation is usually traced to the mid-nineteenth century at the earliest. While it is true that formal specialisation in children's medicine was not, on the whole, typical for eighteenth-century medical practitioners, many displayed a deep and lasting interest in the diseases of children, and were consequently eager to develop therapeutic practices which could be targeted at infants and children. This led to a variety of attempts at innovation, many of which benefitted from the co-operation of, and opportunities afforded by, institutions. By examining the efforts of several medical practitioners at the London Foundling Hospital and at the Dispensary for the Infant Poor, this article explores how eighteenth-century medical practitioners used their affiliations with institutions to address the problems of devising or adapting therapeutic practices and treatments for children. In tailoring medical practice to suit children and, more specifically, in using institutions to do so, medical practitioners were demonstrating that child patients required special consideration, that children's diseases could be managed medically and with the benefit of new approaches and methods, and that children's health, as a whole, was the province of medical practitioners.

Complement therapeutics in inflammatory diseases: promising drug candidates for C3-targeted intervention.

PubMed

Mastellos, D C; Ricklin, D; Hajishengallis, E; Hajishengallis, G; Lambris, J D

2016-02-01

There is increasing appreciation that complement dysregulation lies at the heart of numerous immune-mediated and inflammatory disorders. Complement inhibitors are therefore being evaluated as new therapeutic options in various clinical translation programs and the first clinically approved complement-targeted drugs have profoundly impacted the management of certain complement-mediated diseases. Among the many members of the intricate protein network of complement, the central component C3 represents a 'hot-spot' for complement-targeted therapeutic intervention. C3 modulates both innate and adaptive immune responses and is linked to diverse immunomodulatory systems and biological processes that affect human pathophysiology. Compelling evidence from preclinical disease models has shown that C3 interception may offer multiple benefits over existing therapies or even reveal novel therapeutic avenues in disorders that are not commonly regarded as complement-driven, such as periodontal disease. Using the clinically developed compstatin family of C3 inhibitors and periodontitis as illustrative examples, this review highlights emerging therapeutic concepts and developments in the design of C3-targeted drug candidates as novel immunotherapeutics for oral and systemic inflammatory diseases. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Role of Chromosomal Instability in Cancer and Therapeutic Responses

PubMed Central

Vargas-Rondón, Natalia

2017-01-01

Cancer is one of the leading causes of death, and despite increased research in recent years, control of advanced-stage disease and optimal therapeutic responses remain elusive. Recent technological improvements have increased our understanding of human cancer as a heterogeneous disease. For instance, four hallmarks of cancer have recently been included, which in addition to being involved in cancer development, could be involved in therapeutic responses and resistance. One of these hallmarks is chromosome instability (CIN), a source of genetic variation in either altered chromosome number or structure. CIN has become a hot topic in recent years, not only for its implications in cancer diagnostics and prognostics, but also for its role in therapeutic responses. Chromosomal alterations are mainly used to determine genetic heterogeneity in tumors, but CIN could also reveal treatment efficacy, as many therapies are based on increasing CIN, which causes aberrant cells to undergo apoptosis. However, it should be noted that contradictory findings on the implications of CIN for the therapeutic response have been reported, with some studies associating high CIN with a better therapeutic response and others associating it with therapeutic resistance. Considering these observations, it is necessary to increase our understanding of the role CIN plays not only in tumor development, but also in therapeutic responses. This review focuses on recent studies that suggest possible mechanisms and consequences of CIN in different disease types, with a primary focus on cancer outcomes and therapeutic responses. PMID:29283387

Bioactive Antimicrobial Peptides as Therapeutics for Corneal Wounds and Infections.

PubMed

Griffith, Gina L; Kasus-Jacobi, Anne; Pereira, H Anne

2017-06-01

Significance: More than 2 million eye injuries and infections occur each year in the United States that leave civilians and military members with reduced or complete vision loss due to the lack of effective therapeutics. Severe ocular injuries and infections occur in varied settings including the home, workplace, and battlefields. In this review, we discuss the potential of developing antimicrobial peptides (AMPs) as therapeutics for the treatment of corneal wounds and infections for which the current treatment options are inadequate. Recent Advances: Standard-of-care employs the use of fluorescein dye for the diagnosis of ocular defects and is followed by the use of antibiotics and/or steroids to treat the infection and reduce inflammation. Recent advances for treating corneal wounds include the development of amniotic membrane therapies, wound chambers, and drug-loaded hydrogels. In this review, we will discuss an innovative approach using AMPs with the dual effect of promoting corneal wound healing and clearing infections. Critical Issues: An important aspect of treating ocular injuries is that treatments need to be effective and administered expeditiously. This is especially important for injuries that occur during combat and in individuals who demonstrate delayed wound healing. To overcome gaps in current treatment modalities, bioactive peptides based on naturally occurring cationic antimicrobial proteins are being investigated as new therapeutics. Future Directions: The development of new therapeutics that can treat ocular infections and promote corneal wound healing, including the healing of persistent corneal epithelial defects, would be of great clinical benefit.

The biopsychosocial benefits and shortfalls for armed forces veterans engaged in archaeological activities.

PubMed

Finnegan, Alan

2016-12-01

Organised outdoor activities are advocated as promoting multiple benefits for a veteran's wellbeing, of whom up to 50% have suffered either/both physical and mental health (MH) problems. This has resulted in significant investment in a growing number of outdoor events, one of which is the Defence Archaeology Group (DAG) which utilises the technical and social aspects of field archaeology in the recovery and skill development of injured veterans. To advance knowledge within veterans' MH and wellbeing through an understanding of the potential long term biopsychosocial benefits and shortfalls for veterans undertaking DAG activities. A constructivist grounded theory approach was used to enable identification of the issues from the participant veteran's perspective. DAG archaeological excavations in April and August 2015. Semi-structured interviews with 14 veterans. The qualitative coding resulted in the indication of 18 categories subsumed within four clusters: motivation and access; mental health; veteran and teamwork; therapeutic environment and leadership. The psychological benefits were improved self-esteem, confidence, a reduction in stigma and motivation to seek help. The reduction in situational stressors associated with difficult life conditions also appeared to improve mood, and there was a clear benefit in being in a caring environment where other people actively paid an interest. There were extended social benefits associated with being accepted as part of a team within a familiar military environment, which presented an opportunity to establish friendships and utilise military skill sets. Organised outdoor activities offer multi-factorial hope for veterans searching for ways to ease the transition to civilian life and recover from military stress and trauma. The relaxing and reflective environment within a military setting appears to construct a sense of personal safety and thereby offers therapeutic value. Copyright © 2016 Elsevier Ltd. All rights

Benefits from additives and xylanase during enzymatic hydrolysis of bamboo shoot and mature bamboo.

PubMed

Li, Kena; Wang, Xiao; Wang, Jingfeng; Zhang, Junhua

2015-09-01

Effects of additives (BSA, PEG 6000, and Tween 80) on enzymatic hydrolysis of bamboo shoot and mature bamboo fractions (bamboo green, bamboo timber, bamboo yellow, bamboo node, and bamboo branches) by cellulases and/or xylanase were evaluated. The addition of additives was comparable to the increase of cellulase loadings in the conversion of cellulose and xylan in bamboo fractions. Supplementation of xylanase (1 mg/g DM) with cellulases (10 FPU/g DM) in the hydrolysis of bamboo fractions was more efficient than addition of additives in the production of glucose and xylose. Moreover, addition of additives could further increase the glucose release from different bamboo fractions by cellulases and xylanase. Bamboo green exhibited the lowest hydrolyzability. Almost all of the polysaccharides in pretreated bamboo shoot fractions were hydrolyzed by cellulases with the addition of additives or xylanase. Additives and xylanase showed great potential for reducing cellulase requirement in the hydrolysis of bamboo. Copyright © 2015 Elsevier Ltd. All rights reserved.

Menstrual Migraine: Therapeutic Approaches

PubMed Central

2009-01-01

The development of diagnostic criteria has enabled greater recognition of menstrual migraine as a highly prevalent and disabling condition meriting specific treatment. Although few therapeutic trials have yet been undertaken in accordance with the criteria, the results of those published to date confirm the efficacy of acute migraine drugs for symptomatic treatment. If this approach is insufficient, the predictability of attacks provides the opportunity for perimenstrual prophylaxis. Continuous contraceptive strategies provide an additional option for management, although clinical trial data are limited. Future approaches to treatment could explore the genomic and nongenomic actions of sex steroids. PMID:21180623

Triggering receptor expressed on myeloid cells 2 (TREM2): a potential therapeutic target for Alzheimer disease?

PubMed

Deming, Yuetiva; Li, Zeran; Benitez, Bruno A; Cruchaga, Carlos

2018-06-20

There are currently no effective therapeutics for Alzheimer disease (AD). Clinical trials targeting amyloid beta thus far have shown very little benefit and only in the earliest stages of disease. These limitations have driven research to identify alternative therapeutic targets, one of the most promising is the triggering receptor expressed on myeloid cells 2 (TREM2). Areas covered: Here, we review the literature to-date and discuss the potentials and pitfalls for targeting TREM2 as a potential therapeutic for AD. We focus on research in animal and cell models for AD and central nervous system injury models which may help in understanding the role of TREM2 in disease. Expert opinion: Studies suggest TREM2 plays a key role in AD pathology; however, results have been conflicting about whether TREM2 is beneficial or harmful. More research is necessary before designing TREM2-targeting therapies. Successful therapeutics will most likely be administered early in disease.

20 CFR 655.154 - Additional positive recruitment.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Additional positive recruitment. 655.154... recruitment. (a) Where to conduct additional positive recruitment. The employer must conduct positive recruitment within a multistate region of traditional or expected labor supply where the CO finds that there...

Therapeutic, prophylactic, untoward, and contraceptive effects of combined oral contraceptives: catholic teaching, natural law, and the principle of double effect when deciding to prescribe and use.

PubMed

Casey, Murray Joseph; Salzman, Todd A

2014-01-01

Combined oral contraceptives (COC) have been demonstrated to have significant benefits for the treatment and prevention of disease. These medications also are associated with untoward health effects, and they may be directly contraceptive. Prescribers and users must compare and weigh the intended beneficial health effects against foreseeable but unintended possible adverse effects in their decisions to prescribe and use. Additionally, those who intend to abide by Catholic teachings must consider prohibitions against contraception. Ethical judgments concerning both health benefits and contraception are approached in this essay through an overview of the therapeutic, prophylactic, untoward, and contraceptive effects of COC and discussion of magisterial and traditional Catholic teachings from natural law. Discerning through the principle of double effect, proportionate reason, and evidence gathered from the sciences, medical and moral conclusions are drawn that we believe to be fully compliant with good medicine and Catholic teaching.

Therapeutic scrapbooking: a technique to promote positive coping and emotional strength in parents of pediatric oncology patients.

PubMed

McCarthy, Paula G; Sebaugh, Jill Genone

2011-01-01

Therapeutic scrapbooking is an intervention being used with parents and caregivers of children with cancer. The purpose of the group is to promote hopefulness, mobilize internal strengths, and thereby enhance the parents' and caregivers' coping abilities to benefit pediatric oncology patients. Facilitators, licensed in medical social work, provide a safe environment for participants to verbalize their stories and share their distress. Scrapbooking is a "normal" activity without the negative stigma that a "support group" may carry, minimizing the reluctance to attend this supportive group. Outcome measurements indicate this therapeutic intervention achieves positive results.

Quantifying Components of Drug Expenditure Inflation: The British Columbia Seniors' Drug Benefit Plan

PubMed Central

Morgan, Steven G

2002-01-01

Objective To quantify the relative and absolute importance of different factors contributing to increases in per capita prescription drug costs for a population of Canadian seniors. Data Sources/Study Setting Data consist of every prescription claim from 1985 to 1999 for the British Columbia Pharmacare Plan A, a tax-financed public drug plan covering all community-dwelling British Columbians aged 65 and older. Study Design Changes in per capita prescription drug expenditures are attributed to changes to four components of expenditure inflation: (1) the pattern of exposure to drugs across therapeutic categories; (2) the mix of drugs used within therapeutic categories; (3) the rate of generic drug product selection; and (4) the prices of unchanged products. Data Collection/Extraction Methods Data were extracted from administrative claims files housed at the UBC Centre for Health Services and Policy Research. Principal Findings Changes in drug prices, the pattern of exposure to drugs across therapeutic categories, and the mix of drugs used within therapeutic categories all caused spending per capita to increase. Incentives for generic substitution and therapeutic reference pricing policies temporarily slowed the cost-increasing influence of changes in product selection by encouraging the use of generic drug products and/or cost-effective brand-name products within therapeutic categories. Conclusions The results suggest that drug plans (and patients) would benefit from more concerted efforts to evaluate the relative cost-effectiveness of competing products within therapeutic categories of drugs. PMID:12479495

Agonist anti-GITR antibody significantly enhances the therapeutic efficacy of Listeria monocytogenes-based immunotherapy.

PubMed

Shrimali, Rajeev; Ahmad, Shamim; Berrong, Zuzana; Okoev, Grigori; Matevosyan, Adelaida; Razavi, Ghazaleh Shoja E; Petit, Robert; Gupta, Seema; Mkrtichyan, Mikayel; Khleif, Samir N

2017-08-15

We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4 + and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment. Here we tested the immune and therapeutic efficacy of Listeria-based immunotherapy combination with agonist antibody to glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) in TC-1 mouse tumor model. We evaluated the potency of combination on tumor growth and survival of treated animals and profiled tumor microenvironment for effector and suppressor cell populations. We demonstrate that combination of Listeria-based immunotherapy with agonist antibody to GITR synergizes to improve immune and therapeutic efficacy of treatment in a mouse tumor model. We show that this combinational treatment leads to significant inhibition of tumor-growth, prolongs survival and leads to complete regression of established tumors in 60% of treated animals. We determined that this therapeutic benefit of combinational treatment is due to a significant increase in tumor infiltrating effector CD4 + and CD8 + T cells along with a decrease of inhibitory cells. To our knowledge, this is the first study that exploits Lm-based immunotherapy combined with agonist anti-GITR antibody as a potent treatment strategy that simultaneously targets both the effector and suppressor arms of the immune system, leading to significantly improved anti-tumor efficacy. We believe that our findings depicted in this manuscript provide a promising and translatable strategy that can enhance the overall

Dietary Supplementations as Neuroprotective Therapies: Focus on NT-020 Diet Benefits in a Rat Model of Stroke

PubMed Central

Kaneko, Yuji; Cortes, Lourdes; Sanberg, Cyndy; Acosta, Sandra; Bickford, Paula C.; Borlongan, Cesar V.

2012-01-01

Stroke remains the number one cause of disability in the adult population. Despite scientific progress in our understanding of stroke pathology, only one treatment (tissue plasminogen activator or tPA) is able to afford benefits but to less than 3% of ischemic stroke patients. The development of experimental dietary supplement therapeutics designed to stimulate endogenous mechanisms that confer neuroprotection is likely to open new avenues for exploring stroke therapies. The present review article evaluates the recent literature supporting the benefits of dietary supplementation for the therapy of ischemic stroke. This article focuses on discussing the medical benefits of NT-020 as an adjunct agent for stroke therapy. Based on our preliminary data, a pre-stroke treatment with dietary supplementation promotes neuroprotection by decreasing inflammation and enhancing neurogenesis. However, we recognize that a pre-stroke treatment holds weak clinical relevance. Thus, the main goal of this article is to provide information about recent data that support the assumption of natural compounds as neuroprotective and to evaluate the therapeutic effects of a dietary supplement called NT-020 as in a stroke model. We focus on a systematic assessment of practical treatment parameters so that NT-020 and other dietary supplementations can be developed as an adjunct agent for the prevention or treatment of chronic diseases. We offer rationale for determining the optimal dosage, therapeutic window, and mechanism of action of NT-020 as a dietary supplement to produce neuroprotection when administered immediately after stroke onset. We highlight our long-standing principle in championing both translational and basic science approaches in an effort to fully reveal the therapeutic potential of NT-020 as dietary supplementation in the treatment of stroke. We envision dietary supplementation as an adjunct therapy for stroke at acute, subacute, and even chronic periods. PMID:22837703

Structurally Based Therapeutic Evaluation: A Therapeutic and Practical Approach to Teaching Medicinal Chemistry.

ERIC Educational Resources Information Center

Alsharif, Naser Z.; And Others

1997-01-01

Explains structurally based therapeutic evaluation of drugs, which uses seven therapeutic criteria in translating chemical and structural knowledge into therapeutic decision making in pharmaceutical care. In a Creighton University (Nebraska) medicinal chemistry course, students apply the approach to solve patient-related therapeutic problems in…

Cumulative Childhood Trauma and Therapeutic Alliance: The Moderator Role of Attachment in Adult Patients Consulting in Sex Therapy.

PubMed

Lafrenaye-Dugas, Anne-Julie; Godbout, Natacha; Hébert, Martine

2018-03-05

While it is documented that clients consulting in sex therapy tend to report high rates of childhood interpersonal traumas (e.g., physical, psychological and sexual abuse), which are associated to insecure attachment and poorer therapeutic alliance, the interrelations of these variables have not yet been evaluated in this specific population. This study examined the associations between attachment, cumulative trauma and therapeutic alliance in 278 sex therapy patients who filled out self-report questionnaires. Results revealed that avoidant attachment acted as a moderator between cumulative trauma and the agreement on tasks dimension of therapeutic alliance. Results suggests the relevance for sex therapists to investigate past traumas and current attachment representations to guide interventions and optimize treatment benefits.

Therapeutic monoclonal antibodies for respiratory diseases: Current challenges and perspectives, March 31 – April 1, 2016, Tours, France

PubMed Central

Desoubeaux, Guillaume; Reichert, Janice M.; Sleeman, Matthew; Reckamp, Karen L.; Ryffel, Bernhard; Adamczewski, Jörg P.; Sweeney, Theresa D.; Vanbever, Rita; Diot, Patrice; Owen, Caroline A.; Page, Clive; Lerondel, Stéphanie; Le Pape, Alain; Heuze-Vourc'h, Nathalie

2016-01-01

ABSTRACT Monoclonal antibody (mAb) therapeutics have tremendous potential to benefit patients with lung diseases, for which there remains substantial unmet medical need. To capture the current state of mAb research and development in the area of respiratory diseases, the Research Center of Respiratory Diseases (CEPR-INSERM U1100), the Laboratory of Excellence “MAbImprove,” the GDR 3260 “Antibodies and therapeutic targeting,” and the Grant Research program ARD2020 “Biotherapeutics” invited speakers from industry, academic and government organizations to present their recent research results at the Therapeutic Monoclonal Antibodies for Respiratory Diseases: Current challenges and perspectives congress held March 31 – April 1, 2016 in Tours, France. PMID:27266390

Cyclic peptides as potential therapeutic agents for skin disorders.

PubMed

Namjoshi, Sarika; Benson, Heather A E

2010-01-01

There is an increasing understanding of the role of peptides in normal skin function and skin disease. With this knowledge, there is significant interest in the application of peptides as therapeutics in skin disease or as cosmeceuticals to enhance skin appearance. In particular, antimicrobial peptides and those involved in inflammatory processes provide options for the development of new therapeutic directions in chronic skin conditions such as psoriasis and dermatitis. To exploit their potential, it is essential that these peptides are delivered to their site of action in active form and in sufficient quantity to provide the desired effect. Many polymers permeate the skin poorly and are vulnerable to enzymatic degradation. Synthesis of cyclic peptide derivatives can substantially alter the physicochemical characteristics of the peptide with the potential to improve its skin permeation. In addition, cyclization can stabilize the peptide structure and thereby increase its stability. This review describes the role of cyclic peptides in the skin, examples of current cyclic peptide therapeutic products, and the potential for cyclic peptides as dermatological therapeutics and cosmeceuticals.

Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

PubMed Central

Hayakawa, Kazuhide; Mishima, Kenichi; Fujiwara, Michihiro

2010-01-01

Cannabis contains the psychoactive component delta9-tetrahydrocannabinol (delta9-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol. It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta9-THC also mediates psychological effects through the activation of the CB1 receptor in the central nervous system. In addition to the CB1 receptor agonists, cannabis also contains therapeutically active components which are CB1 receptor independent. Of the CB1 receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke. PMID:27713349

Emerging therapeutic uses of direct-acting oral anticoagulants: An evidence-based perspective.

PubMed

Raschi, Emanuel; Bianchin, Matteo; De Ponti, Roberto; De Ponti, Fabrizio; Ageno, Walter

2017-06-01

Direct-acting oral anticoagulants (DOACs) were claimed to cause a potential paradigm shift in the therapeutic scenario of patients requiring short- and long-term anticoagulation, by virtue of their pharmacological properties, perceived as innovative. The evidence gathered so far (from pre-approval pivotal trials to real-world post-marketing observational data) consistently confirmed that DOACs are overall comparable to vitamin-K antagonists (VKAs) in terms of safety, efficacy and effectiveness and unequivocally documented a consistent and clinically relevant reduced risk of intracranial bleeding in the settings of non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE). Interestingly, two parallel paths can be identified in the current research scenario: A) in the aforementioned consolidated therapeutic indications, an innovative approach is directed towards tailored treatment strategies, to identify patients most likely to benefit from one of the different anticoagulant drugs, in particular subpopulations at increased risk of adverse events (e.g., bleeding); B) in unconventional settings, DOACs are gaining interest for potential use in emerging diseases characterized by arterial and venous thromboembolic risk. In these scenarios, the risk-benefit profile of DOACs, as compared to VKAs or heparins, is less defined. The aim of this review is to critically assess the body of evidence underlying emerging therapeutic uses of DOACs (e.g., heparin-induced thrombocytopenia, anti-phospholipid antibody syndrome), including evolving issues in special populations (e.g., patients with VTE and cancer or cirrhosis). This will be achieved by analyzing the strength (i.e., systematic reviews, randomized clinical trials, observational studies, case report/series) and consistency (i.e., concordance) of both published and unpublished evidence registered in major public repositories. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanisms of Plasma Therapeutics

NASA Astrophysics Data System (ADS)

Graves, David

2015-09-01

In this talk, I address research directed towards biomedical applications of atmospheric pressure plasma such as sterilization, surgery, wound healing and anti-cancer therapy. The field has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that plasmas readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. It is postulated that cold atmospheric plasma (CAP) can trigger a therapeutic shielding response in tissue in part by creating a time- and space-localized, burst-like form of oxy-nitrosative stress on near-surface exposed cells through the flux of plasma-generated RONS. RONS-exposed surface layers of cells communicate to the deeper levels of tissue via a form of the ``bystander effect,'' similar to responses to other forms of cell stress. In this proposed model of CAP therapeutics, the plasma stimulates a cellular survival mechanism through which aerobic organisms shield themselves from infection and other challenges.

Therapeutic polymers for dental adhesives: Loading resins with bio-active components

PubMed Central

Imazato, Satoshi; Ma, Sai; Chen, Ji-hua; Xu, Hockin H.K.

2014-01-01

Objectives Many recent adhesives on the market exhibit reasonable clinical performance. Future innovations in adhesive materials should therefore seek out novel properties rather than simply modifying existing technologies. It is proposed that adhesive materials that are “bio-active” could contribute to better prognosis of restorative treatments. Methods This review examines the recent approaches used to achieve therapeutic polymers for dental adhesives by incorporating bio-active components. A strategy to maintain adhesive restorations is the focus of this paper. Results Major trials on therapeutic dental adhesives have looked at adding antibacterial activities or remineralization effects. Applications of antibacterial resin monomers based on quaternary ammonium compounds have received much research attention, and the loading of nano-sized bioactive particles or multiple ion-releasing glass fillers have been perceived as advantageous since they are not expected to influence the mechanical properties of the carrier polymer. Significance The therapeutic polymer approaches described here have the potential to provide clinical benefits. However, not many technological applications in this category have been successfully commercialized. Clinical evidence as well as further advancement of these technologies can be a driving force to make these new types of materials clinically available. PMID:23899387

Physical dose of therapeutic exercises in institutional neck rehabilitation.

PubMed

Wasenius, Niko; Karapalo, Teppo; Sjögren, Tuulikki; Pekkonen, Mika; Mälkiä, Esko

2013-03-01

To determine the intensity and volume of therapeutic exercises during a standard 13-day inpatient neck rehabilitation course in relation to overall physical activity in rehabilitation and everyday life. Cross-sectional study. Subjects (n = 19; 16 women and 3 men; mean age 48.6 years, standard deviation (SD) 6.6) with chronic non-specific neck pain were recruited from two inpatient neck rehabilitation courses. Intensity and volume of therapeutic exercises and physical activity were measured in metabolic equivalents (METs) with an objective measurement device and all-time recall questionnaire. Maximum oxygen uptake was determined in METs (METc) by direct maximal cycle ergometer. Subjects' mean METc was 7.2 METs (SD 1.4) or 25.3 ml/kg/min (SD 4.8). Intensity of all therapeutic exercises was 1.9 METs or 27 %METc (SD 5.1) and volume 7.7 MET-hours/week. Intensity of specific neck and shoulder exercises was 2.0 METs or 28 %METc (SD 5.4) and volume 2.5 MET-hours/week. In addition, subjects were more active in everyday life than in inpatient rehabilitation. The therapeutic exercise dose failed to reach previously reported target values for pain relief. The dose of therapeutic exercises and confounding physical activity should be carefully controlled in pain rehabilitation programmes.

Exploring the Therapeutic Affordances of Self-Harm Online Support Communities: An Online Survey of Members

PubMed Central

Bullock, Emma

2017-01-01

Background A growing number of online communities have been established to support those who self-harm. However, little is known about the therapeutic affordances arising from engagement with these communities and resulting outcomes. Objective The aim of this study was to explore the presence of therapeutic affordances as reported by members of self-harm online support communities. Methods In total, 94 respondents (aged 13-63 years, mean=23.5 years; 94% female) completed an online survey exploring their experiences of engaging with a self-harm online support community. Respondents varied in terms of how long they had been accessing an online community, with 22% (21/94) accessing less than 1 year, 39% (37/94) 1 to 2 years, 14% (13/94) 2 to 3 years, and 24.5% (23/94) more than 3 years. Responses were analyzed using deductive thematic analysis. Results The results of our analysis describe each of the five therapeutic affordances that were present in the data, namely (1) connection, the ability to make contact with others who self-harm for the purposes of mutual support and in so doing reduce feelings of loneliness and isolation; (2) adaptation, that is, how use of online support varies in relation to the personal circumstances of the individual user; (3) exploration, that is, the ability to learn about self-harm and learn about strategies to reduce or stop self-harming behavior; (4) narration, that is, the ability to share experiences, as well as read about the experiences of others; and (5) self-presentation, that is, how and what users present about themselves to others in the online community. Conclusions Our findings suggest that engagement with self-harm online support communities may confer a range of therapeutic benefits for some users, which may serve to minimize the psychosocial burden of self-harm and promote positive coping strategies. In addition, the online nature of the support available may be helpful to those who are unable to access face

5 CFR 831.407 - Purchase of additional annuity.

Code of Federal Regulations, 2010 CFR

2010-01-01

... benefit, each $100 credited to his or her voluntary contribution account, including interest, purchases an additional annuity at the rate of $7 per year, plus 20 cents for each full year, if any, he or she is over... benefit, each $100 credited to his or her voluntary contribution account, including interest, purchases an...

Canonical and non-canonical barriers facing antimiR cancer therapeutics.

PubMed

Cheng, Christopher J; Saltzman, W Mark; Slack, Frank J

2013-01-01

Once considered genetic "oddities", microRNAs (miRNAs) are now recognized as key epigenetic regulators of numerous biological processes, including some with a causal link to the pathogenesis, maintenance, and treatment of cancer. The crux of small RNA-based therapeutics lies in the antagonism of potent cellular targets; the main shortcoming of the field in general, lies in ineffective delivery. Inhibition of oncogenic miRNAs is a relatively nascent therapeutic concept, but as with predecessor RNA-based therapies, success hinges on delivery efficacy. This review will describes the canonical (e.g. pharmacokinetics and clearance, cellular uptake, endosome escape, etc.) and non-canonical (e.g. spatial localization and accessibility of miRNA, technical limitations of miRNA inhibition, off-target impacts, etc.) challenges to the delivery of antisense-based anti-miRNA therapeutics (i.e. antimiRs) for the treatment of cancer. Emphasis will be placed on how the current leading antimiR platforms-ranging from naked chemically modified oligonucleotides to nanoscale delivery vehicles-are affected by and overcome these barriers. The perplexity of antimiR delivery presents both engineering and biological hurdles that must be overcome in order to capitalize on the extensive pharmacological benefits of antagonizing tumor-associated miRNAs.

[The nurses involved in therapeutic innovation].

PubMed

Cheron, Coralie

2016-03-01

Clinical research nurses (CRNs) play an important role within the teams involved in the fight against cancer and in therapeutic innovation. In the dermatology department of the Gustave-Roussy Institute, patients treated for melanoma and taking part in clinical trials are supported along their care pathway by a CRN who, in addition to her clinical expertise, acts as a link between the different players concerned. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

[Therapeutic massage on behavioral disturbances of elderly patients with dementia].

PubMed

Barquilla Ávila, Carolina; Rodríguez-Mansilla, Juan

2015-12-01

To know the efficacy of therapeutic massage on behavioral disturbances of elderly patients with dementia. Literature review. The literature search was done in six scientific databases: PubMed, Cochrane Library Plus, PEDro, Dialnet, Scopus and CSIC, between 1983 and 2013. The search terms were "massage", "dementia", "therapy", "behavior disorders" and "Alzheimer". Of the 496 articles analyzed, 11 scientific articles have met the selection criteria. Inclusion criteria were: clinical trials, published in English or Spanish, which had analyzed the effects of massage therapy on altered behaviors in people with dementia. The variables were massage benefits, type of massage and massage lubricant. Their authors use different massage techniques (effleurage, pétrissage, pressures, frictions and kneading), obtain better conduct disorders (aggression, anxiety, agitation, and resistance to care) of elderly. The therapeutic massage can be a complementary treatment in the rehabilitation program for better behavior disorders. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

On the TRAIL to successful cancer therapy? Predicting and counteracting resistance against TRAIL-based therapeutics

PubMed Central

Dimberg, Lina Y.; Anderson, Charles K.; Camidge, Ross; Behbakht, Kian; Thorburn, Andrew; Ford, Heide L.

2015-01-01

TRAIL and agonistic antibodies against TRAIL death receptors kill tumor cells while causing virtually no damage to normal cells. Several novel drugs targeting TRAIL receptors are currently in clinical trials. However, TRAIL resistance is a common obstacle in TRAIL based therapy and limits the efficiency of these drugs. In this review article we discuss different mechanisms of TRAIL resistance and how they can be predicted and therapeutically circumvented. In addition, we provide a brief overview of all TRAIL based clinical trials conducted so far. It is apparent that although the effects of TRAIL therapy are disappointingly modest overall, a small subset of patients responds very well to TRAIL. We argue that the true potential of targeting TRAIL death receptors in cancer can only be reached when we find efficient ways to select for those patients that are most likely to benefit from the treatment. To achieve this, it is crucial to identify biomarkers that can help us predict TRAIL sensitivity. PMID:22580613

Updates in hyperkalemia: Outcomes and therapeutic strategies.

PubMed

Kovesdy, Csaba P

2017-03-01

Hyperkalemia is a frequent clinical abnormality in patients with chronic kidney disease, and it is associated with higher risk of mortality and malignant arrhythmias. Severe hyperkalemia is a medical emergency, which requires immediate therapies, followed by interventions aimed at preventing its recurrence. Current treatment paradigms for chronic hyperkalemia management are focused on eliminating predisposing factors, such as high potassium intake in diets or supplements, and the use of medications known to raise potassium level. Among the latter, inhibitors of the renin-angiotensin aldosterone system are some of the most commonly involved medications, and their discontinuation is often the first step taken by clinicians to prevent the recurrence of hyperkalemia. While this strategy is usually successful, it also deprives patients of the recognized benefits of this class, such as their renoprotective effects. The development of novel potassium binders has ushered in a new era of hyperkalemia management, with a focus on chronic therapy while maintaining the use of beneficial, but hyperkalemia-inducing medications such as renin-angiotensin aldosterone system inhibitors. This review article examines the incidence and clinical consequences of hyperkalemia, and its various treatment options, with special emphasis on novel therapeutic agents and the potential benefits of their application.

The Benefit of Additional Oviposition Targets for a Polyphagous Butterfly

PubMed Central

Johansson, Josefin; Bergström, Anders; Janz, Niklas

2007-01-01

While the reasons for the prevalence of specialists over generalists among herbivorous insects have been at the focus of much interest, less effort has been put into understanding the polyphagous exceptions. Recent studies have suggested that these exceptions may be important for insect diversification, which calls for a better understanding of the potential factors that can lead to an increased host plant repertoire. Females of the Nymphalid butterfly, Polygonia c-album, were used to test if egg output and/or likelihood of finding a host increased with the addition of a secondary host. There was no effect of prior eggs on the host for willingness to oviposit on a plant. The main experiments were conducted both in small laboratory cages and in large outdoor experimental arenas. No positive effect was found when another oviposition target was added in small cages in the laboratory. On the other hand, in the outdoor arenas the females more often found a host to oviposit on and had a higher egg output when they had access to an additional host, even though the second host was lower in their preference hierarchy. The difference between these experiments was attributed to searching for acceptable host plants within a patch, a factor that was included in the large cages but not in the small. When host availability is limited, adding oviposition targets can potentially act to counterbalance specialization and thus favor the evolution of generalization. PMID:20334600

Potential Benefit of Singing for People with Parkinson's Disease: A Systematic Review.

PubMed

Barnish, Jean; Atkinson, Rachel A; Barran, Susannah M; Barnish, Maxwell S

2016-06-03

There is evidence that participation in performing arts brings psychosocial benefits in the general population and in recent years there has been substantial interest in the potential therapeutic benefit of performing arts, including singing, for people with chronic medical conditions including those of neurological aetiology. To systematically review the existing body of evidence regarding the potential benefit of singing on clinical outcomes of people with PD. Seven online bibliographic databases were systematically searched in January 2016 and supplementary searches were conducted. Full-text original peer-reviewed scientific papers that investigated the potential benefit of singing on at least one of speech, functional communication, cognitive status, motor function and quality of life in human participants with PD were eligible for inclusion. 449 unique records were identified, 25 full-text articles were screened and seven studies included in the review. All seven studies assessed the impact of singing on speech, five found partial evidence of benefit and two found no evidence of benefit. One study assessed each of functional communication and quality of life and no significant benefit was found. No included study assessed the impact of singing on motor function or cognitive status. Singing may benefit the speech of people with PD, although evidence is not unequivocal. Further research is required to assess wider benefits including on functional communication, cognitive status, motor function and quality of life. Substantial methodological limitations were identified in the existing literature. Recommendations are made for advancing the state of the literature.

Physician assessments of the value of therapeutic information delivered via e-mail

PubMed Central

Grad, Roland; Pluye, Pierre; Repchinsky, Carol; Jovaisas, Barbara; Marlow, Bernard; Marques Ricarte, Ivan L.; Galvão, Maria Cristiane Barbosa; Shulha, Michael; de Gaspé Bonar, James

2014-01-01

Abstract Problem addressed Although e-learning programs are popular and access to electronic knowledge resources has improved, raising awareness about updated therapeutic recommendations in practice continues to be a challenge. Objective of program To raise awareness about and document the use of therapeutic recommendations. Program description In 2010, family physicians evaluated e-Therapeutics (e-T) Highlights with a Web-based tool called the Information Assessment Method (IAM). The e-T Highlights consisted of information found in the primary care reference e-Therapeutics+. Each week, family physicians received an e-mail containing a link to 1 Highlight from a different chapter of e-Therapeutics+. Family physicians received continuing medical education credits for each Highlight they rated with the IAM. Of the 5346 participants, 85% of them were full-time or part-time practitioners. A total of 31 429 Highlights ratings were received in 2010 (median of 2 ratings per participant, range 1 to 49). Among participants who rated more than 2 Highlights, the median number of ratings was 7 (mean 11.9). The relevance of the information from individual Highlights varied widely; however, for 90% of the rated Highlights participants indicated total or partial relevance of the information for at least 1 patient. For 41% of rated Highlights, participants expected patient health benefits to result from implementing the recommendation, such as avoiding an unnecessary or inappropriate treatment, or a preventive intervention. Conclusion This continuing medical education program stimulated family physicians to rate therapeutic recommendations that were delivered weekly via e-mail. The process of rating e-T Highlights with the IAM raised awareness about treatment recommendations and documented self-reported use of this information in practice. PMID:24829020

Social Workers' Reflections on the Therapeutic Encounter With Elder Abuse and Neglect.

PubMed

Goldblatt, Hadass; Band-Winterstein, Tova; Alon, Sara

2016-02-24

The aim of this qualitative study was to explore social workers' reflections on their experience of the therapeutic encounter with victims and perpetrators of elder abuse and neglect. The research questions were as follows: How do social workers tune themselves toward the therapeutic encounter with elder abuse? How do they position themselves vis-à-vis the clients? How do social workers describe the meaning of the intervention both for the clients and for themselves? What is the added value of the therapeutic encounter in this field for the social workers? Participants were 17 experienced women social workers, who worked with abusers and with abused and neglected older adults in Israel. Data were collected via in-depth semi-structured interviews, which were later transcribed and content analyzed. Two main themes emerged from the findings, emphasizing two key aspects of the social workers' reflective process experienced during the therapeutic encounter: (a) focus on the client: "This is the journey of their lives"-reflection on the therapeutic "journey"; (b) focus on the social worker's inner and professional world: "'There is nothing to be done' is no longer in my vocabulary"-a personal and professional maturation process. The social workers expressed a positive attitude toward their elder clients. A unique dialogue developed in the therapeutic encounter, whereby the social workers considered any change as valuable if it allowed the elders a sense of control and self-worth, whereas the social workers were enriched by the elders' life experience, and matured both personally and professionally. Thus, both sides benefited from this reciprocal relationship. Implications for further research and practice are discussed. © The Author(s) 2016.

Protein-Based Therapeutic Killing for Cancer Therapies.

PubMed

Serna, Naroa; Sánchez-García, Laura; Unzueta, Ugutz; Díaz, Raquel; Vázquez, Esther; Mangues, Ramón; Villaverde, Antonio

2018-03-01

The treatment of some high-incidence human diseases is based on therapeutic cell killing. In cancer this is mainly achieved by chemical drugs that are systemically administered to reach effective toxic doses. As an innovative alternative, cytotoxic proteins identified in nature can be adapted as precise therapeutic agents. For example, individual toxins and venom components, proapoptotic factors, and antimicrobial peptides from bacteria, animals, plants, and humans have been engineered as highly potent drugs. In addition to the intrinsic cytotoxic activities of these constructs, their biological fabrication by DNA recombination allows the recruitment, in single pharmacological entities, of diverse functions of clinical interest such as specific cell-surface receptor binding, self-activation, and self-assembling as nanoparticulate materials, with wide applicability in cell-targeted oncotherapy and theragnosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Therapeutic applications of circadian rhythms for the cardiovascular system

PubMed Central

Tsimakouridze, Elena V.; Alibhai, Faisal J.; Martino, Tami A.

2015-01-01

The cardiovascular system exhibits dramatic time-of-day dependent rhythms, for example the diurnal variation of heart rate, blood pressure, and timing of onset of adverse cardiovascular events such as heart attack and sudden cardiac death. Over the past decade, the circadian clock mechanism has emerged as a crucial factor regulating these daily fluctuations. Most recently, these studies have led to a growing clinical appreciation that targeting circadian biology offers a novel therapeutic approach toward cardiovascular (and other) diseases. Here we describe leading-edge therapeutic applications of circadian biology including (1) timing of therapy to maximize efficacy in treating heart disease (chronotherapy); (2) novel biomarkers discovered by testing for genomic, proteomic, metabolomic, or other factors at different times of day and night (chronobiomarkers); and (3) novel pharmacologic compounds that target the circadian mechanism with potential clinical applications (new chronobiology drugs). Cardiovascular disease remains a leading cause of death worldwide and new approaches in the management and treatment of heart disease are clearly warranted and can benefit patients clinically. PMID:25941487

Hedgehog Signaling in Prostate Cancer and Its Therapeutic Implication

PubMed Central

Gonnissen, Annelies; Isebaert, Sofie; Haustermans, Karin

2013-01-01

Activation of Hedgehog (Hh) signaling is implicated in the development and progression of several tumor types, including prostate cancer, which is still the most common non-skin malignancy and the third leading cause of cancer-related mortality in men in industrialized countries worldwide. Several studies have indicated that the Hh pathway plays a crucial role in the development as well as in the progression of this disease to more aggressive and even therapy-resistant disease states. Moreover, preclinical data have shown that inhibition of Hh signaling has the potential to reduce prostate cancer invasiveness and metastatic potential. Clinical trials investigating the benefit of Hh inhibitors in patients with prostate cancer have recently been initiated. However, acquired drug resistance has already been observed in other tumor types after long-term Hh inhibition. Therefore, combining Hh inhibitors with ionizing radiation, chemotherapy or other molecular targeted agents could represent an alternative therapeutic strategy. In this review, we will highlight the role of Hh signaling in the development and progression of prostate cancer and summarize the different therapeutic applications of Hedgehog inhibition. PMID:23880852

Aqueous Plasma Pharmacy: Preparation Methods, Chemistry, and Therapeutic Applications

PubMed Central

Joslin, Jessica M.; McCall, James R.; Bzdek, Justin P.; Johnson, Derek C.; Hybertson, Brooks M.

2017-01-01

Plasma pharmacy is a subset of the broader field of plasma medicine. Although not strictly defined, the term aqueous plasma pharmacy (APP) is used to refer to the generation and distribution of reactive plasma-generated species in an aqueous solution followed by subsequent administration for therapeutic benefits. APP attempts to harness the therapeutic effects of plasma-generated oxidant species within aqueous solution in various applications, such as disinfectant solutions, cell proliferation related to wound healing, and cancer treatment. The subsequent use of plasma-generated solutions in the APP approach facilitates the delivery of reactive plasma species to internal locations within the body. Although significant efforts in the field of plasma medicine have concentrated on employing direct plasma plume exposure to cells or tissues, here we focus specifically on plasma discharge in aqueous solution to render the solution biologically active for subsequent application. Methods of plasma discharge in solution are reviewed, along with aqueous plasma chemistry and the applications for APP. The future of the field also is discussed regarding necessary research efforts that will enable commercialization for clinical deployment. PMID:28428835

Overview of Levee Setback Projects and Benefits

DTIC Science & Technology

2017-07-31

VII-17 July 2017 2 Levee setback projects do not necessarily remove or relocate an entire levee (USACE 2012). Levee alterations that create “ managed ...reduction or environmental improvement. For individual projects , there may also be additional economic and societal benefits. Flood Risk Management ...ERDC/CHL CHETN-VII-17 July 2017 Approved for public release; distribution is unlimited. Overview of Levee Setback Projects and Benefits by

26 CFR 53.4958-1 - Taxes on excess benefit transactions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... organization (as defined in section 4958(e) and § 53.4958-2) and a disqualified person (as defined in section... imposed is liable for an additional tax of 200 percent of the excess benefit. An organization manager (as... reasonable cause. If an organization manager also receives an excess benefit from an excess benefit...

Garlic: a review of potential therapeutic effects

PubMed Central

Bayan, Leyla; Koulivand, Peir Hossain; Gorji, Ali

2014-01-01

Throughout history, many different cultures have recognized the potential use of garlic for prevention and treatment of different diseases. Recent studies support the effects of garlic and its extracts in a wide range of applications. These studies raised the possibility of revival of garlic therapeutic values in different diseases. Different compounds in garlic are thought to reduce the risk for cardiovascular diseases, have anti-tumor and anti-microbial effects, and show benefit on high blood glucose concentration. However, the exact mechanism of all ingredients and their long-term effects are not fully understood. Further studies are needed to elucidate the pathophysiological mechanisms of action of garlic as well as its efficacy and safety in treatment of various diseases. PMID:25050296

DNA and aptamer stabilized gold nanoparticles for targeted delivery of anticancer therapeutics

NASA Astrophysics Data System (ADS)

Latorre, Alfonso; Posch, Christian; Garcimartín, Yolanda; Celli, Anna; Sanlorenzo, Martina; Vujic, Igor; Ma, Jeffrey; Zekhtser, Mitchell; Rappersberger, Klemens; Ortiz-Urda, Susana; Somoza, Álvaro

2014-06-01

Gold nanoparticles (GNPs) can be used as carriers of a variety of therapeutics. Ideally, drugs are released in the target cells in response to cell specific intracellular triggers. In this study, GNPs are loaded with doxorubicin or AZD8055, using a self-immolative linker which facilitates the release of anticancer therapeutics in malignant cells without modifications of the active compound. An additional modification with the aptamer AS1411 further increases the selectivity of GNPs towards cancer cells. Both modifications increase targeted delivery of therapeutics with GNPs. Whereas GNPs without anticancer drugs do not affect cell viability in all cells tested, AS1411 modified GNPs loaded with doxorubicin or AZD8055 show significant and increased reduction of cell viability in breast cancer and uveal melanoma cell lines. These results highlight that modified GNPs can be functionalized to increase the efficacy of cancer therapeutics and may further reduce toxicity by increasing targeted delivery towards malignant cells.Gold nanoparticles (GNPs) can be used as carriers of a variety of therapeutics. Ideally, drugs are released in the target cells in response to cell specific intracellular triggers. In this study, GNPs are loaded with doxorubicin or AZD8055, using a self-immolative linker which facilitates the release of anticancer therapeutics in malignant cells without modifications of the active compound. An additional modification with the aptamer AS1411 further increases the selectivity of GNPs towards cancer cells. Both modifications increase targeted delivery of therapeutics with GNPs. Whereas GNPs without anticancer drugs do not affect cell viability in all cells tested, AS1411 modified GNPs loaded with doxorubicin or AZD8055 show significant and increased reduction of cell viability in breast cancer and uveal melanoma cell lines. These results highlight that modified GNPs can be functionalized to increase the efficacy of cancer therapeutics and may further

Thiol–ene click hydrogels for therapeutic delivery

PubMed Central

Kharkar, Prathamesh M.; Rehmann, Matthew S.; Skeens, Kelsi M.; Maverakis, Emanual; Kloxin, April M.

2016-01-01

Hydrogels are of growing interest for the delivery of therapeutics to specific sites in the body. For use as a delivery vehicle, hydrophilic precursors are usually laden with bioactive moieties and then directly injected to the site of interest for in situ gel formation and controlled release dictated by precursor design. Hydrogels formed by thiol–ene click reactions are attractive for local controlled release of therapeutics owing to their rapid reaction rate and efficiency under mild aqueous conditions, enabling in situ formation of gels with tunable properties often responsive to environmental cues. Herein, we will review the wide range of applications for thiol–ene hydrogels, from the prolonged release of anti-inflammatory drugs in the spine to the release of protein-based therapeutics in response to cell-secreted enzymes, with a focus on their clinical relevance. We will also provide a brief overview of thiol–ene click chemistry and discuss the available alkene chemistries pertinent to macromolecule functionalization and hydrogel formation. These chemistries include functional groups susceptible to Michael type reactions relevant for injection and radically-mediated reactions for greater temporal control of formation at sites of interest using light. Additionally, mechanisms for the encapsulation and controlled release of therapeutic cargoes are reviewed, including i) tuning the mesh size of the hydrogel initially and temporally for cargo entrapment and release and ii) covalent tethering of the cargo with degradable linkers or affinity binding sequences to mediate release. Finally, myriad thiol–ene hydrogels and their specific applications also are discussed to give a sampling of the current and future utilization of this chemistry for delivery of therapeutics, such as small molecule drugs, peptides, and biologics. PMID:28361125

Theranostics Using Antibodies and Antibody-Related Therapeutics.

PubMed

Moek, Kirsten L; Giesen, Danique; Kok, Iris C; de Groot, Derk Jan A; Jalving, Mathilde; Fehrmann, Rudolf S N; Lub-de Hooge, Marjolijn N; Brouwers, Adrienne H; de Vries, Elisabeth G E

2017-09-01

In theranostics, radiolabeled compounds are used to determine a treatment strategy by combining therapeutics and diagnostics in the same agent. Monoclonal antibodies (mAbs) and antibody-related therapeutics represent a rapidly expanding group of cancer medicines. Theranostic approaches using these drugs in oncology are particularly interesting because antibodies are designed against specific targets on the tumor cell membrane and immune cells as well as targets in the tumor microenvironment. In addition, these drugs are relatively easy to radiolabel. Noninvasive molecular imaging techniques, such as SPECT and PET, provide information on the whole-body distribution of radiolabeled mAbs and antibody-related therapeutics. Molecular antibody imaging can potentially elucidate drug target expression, tracer uptake in the tumor, tumor saturation, and heterogeneity for these parameters within the tumor. These data can support drug development and may aid in patient stratification and monitoring of the treatment response. Selecting a radionuclide for theranostic purposes generally starts by matching the serum half-life of the mAb or antibody-related therapeutic and the physical half-life of the radionuclide. Furthermore, PET imaging allows better quantification than the SPECT technique. This information has increased interest in theranostics using PET radionuclides with a relatively long physical half-life, such as 89 Zr. In this review, we provide an overview of ongoing research on mAbs and antibody-related theranostics in preclinical and clinical oncologic settings. We identified 24 antibodies or antibody-related therapeutics labeled with PET radionuclides for theranostic purposes in patients. For this approach to become integrated in standard care, further standardization with respect to the procedures involved is required. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Applying 'evidence-based medicine' theory to interventional radiology. Part 2: a spreadsheet for swift assessment of procedural benefit and harm.

PubMed

Maceneaney, P M; Malone, D E

2000-12-01

To design a spreadsheet program to analyse interventional radiology (IR) data rapidly produced in local research or reported in the literature using 'evidence-based medicine' (EBM) parameters of treatment benefit and harm. Microsoft Excel(TM)was used. The spreadsheet consists of three worksheets. The first shows the 'Levels of Evidence and Grades of Recommendations' that can be assigned to therapeutic studies as defined by the Oxford Centre for EBM. The second and third worksheets facilitate the EBM assessment of therapeutic benefit and harm. Validity criteria are described. These include the assessment of the adequacy of sample size in the detection of possible procedural complications. A contingency (2 x 2) table for raw data on comparative outcomes in treated patients and controls has been incorporated. Formulae for EBM calculations are related to these numerators and denominators in the spreadsheet. The parameters calculated are benefit - relative risk reduction, absolute risk reduction, number needed to treat (NNT). Harm - relative risk, relative odds, number needed to harm (NNH). Ninety-five per cent confidence intervals are calculated for all these indices. The results change automatically when the data in the therapeutic outcome cells are changed. A final section allows the user to correct the NNT or NNH in their application to individual patients. This spreadsheet can be used on desktop and palmtop computers. The MS Excel(TM)version can be downloaded via the Internet from the URL ftp://radiography.com/pub/TxHarm00.xls. A spreadsheet is useful for the rapid analysis of the clinical benefit and harm from IR procedures.

A benefit-cost framework of motivation for a specific activity.

PubMed

Studer, B; Knecht, S

2016-01-01

How can an individual be motivated to perform a target exercise or activity? This question arises in training, therapeutic, and education settings alike, yet despite-or even because of-the large range of extant motivation theories, finding a clear answer to this question can be challenging. Here we propose an application-friendly framework of motivation for a specific activity or exercise that incorporates core concepts from several well-regarded psychological and economic theories of motivation. The key assumption of this framework is that motivation for performing a given activity is determined by the expected benefits and the expected costs of (performance of) the activity. Benefits comprise positive feelings, gains, and rewards experienced during performance of the activity (intrinsic benefits) or achieved through the activity (extrinsic benefits). Costs entail effort requirements, time demands, and other expenditure (intrinsic costs) as well as unwanted associated outcomes and missing out on alternative activities (extrinsic costs). The expected benefits and costs of a given exercise are subjective and state dependent. We discuss convergence of the proposed framework with a selection of extant motivation theories and briefly outline neurobiological correlates of its main components and assumptions. One particular strength of our framework is that it allows to specify five pathways to increasing motivation for a target exercise, which we illustrate and discuss with reference to previous empirical data. © 2016 Elsevier B.V. All rights reserved.

Program Benefits Guidance: Analysis of Benefits Associated with Projects and Technologies Supported by the Alternative and Renewable Fuel and Vehicle Technology Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Melaina, Marc; Warner, Ethan; Sun, Yongling

The Alternative and Renewable Fuel and Vehicle Technologies Program (ARFVTP) supports a wide range of alternative, low-carbon fuel and vehicle projects in California. This report focuses on two types of ARFVTP benefits. Expected benefits reflect successful deployment of vehicles and fuels supported through program projects. Market transformation benefits represent benefits resulting from project influences on future market conditions to accelerated technology adoption rates. Data collected directly from ARFVTP projects funded from 2009 to first quarter 2014 are used as inputs to the benefits analysis, where possible. Expected benefit estimation methods rely primarily upon project-level data and result in year single-pointmore » estimates within the 2011 to 2025 analysis period. Results suggest that the 178 projects evaluated for expected benefits, representing an investment of $351.3 million in ARFVTP funds, could result in a reduction in petroleum fuel use by 236 million gallons per year and greenhouse gases (GHGs) by 1.7 million metric tonnes carbon dioxide equivalent (MMTCO2e) per year by 2025. Market transformation benefits are described as accruing in addition to expected benefits. They are inherently more uncertain and theoretical than expected benefits, and are therefore reported as high and low ranges, with results suggesting reductions of 1.1 MMTCO2e to 2.5 MMTCO2e per year in GHG reductions and 102 million to 330 million gallons per year in petroleum fuel reductions by 2025. Taking both benefit types into account, results suggest that ARFVTP projects have the potential to make substantial progress toward meeting California's long-term GHG and petroleum fuel use reduction goals. As additional project data become available and market success with alternative and renewable fuels and vehicles grows, the analytic framework relied upon to develop these estimates will become more rigorous and will have a greater capacity to inform future ARFVTP activities.« less

The Therapeutic Roller Coaster

PubMed Central

CHU, JAMES A.

1992-01-01

Survivors of severe childhood abuse often encounter profound difficulties. In addition to posttraumatic and dissociative symptomatology, abuse survivors frequently have characterologic problems, particularly regarding self-care and maintaining relationships. Backgrounds of abuse, abandonment, and betrayal are often recapitulated and reenacted in therapy, making the therapeutic experience arduous and confusing for therapists and patients. Efforts must be directed at building an adequate psychotherapeutic foundation before undertaking exploration and abreaction of past traumatic experiences. This discussion sets out a model for treatment of childhood abuse survivors, describing stages of treatment and suggesting interventions. Common treatment dilemmas or "traps" are discussed, with recommendations for their resolution. PMID:22700116

On the advancement of therapeutic penality: therapeutic authority, personality science and the therapeutic community.

PubMed

McBride, Ruari-Santiago

2017-09-01

In this article I examine the advancement of therapeutic penality in the UK, a penal philosophy that reimagines prison policy, practices and environments utilising psychological knowledge. Adopting a historical approach, I show how modern therapeutic penality is linked to the emergence of personality science in the nineteenth century and the development of the democratic therapeutic community (DTC) model in the twentieth century. I outline how at the turn of the twenty-first century a catalytic event generated a moral panic that led the British government to mobilise psychological knowledge and technologies in an attempt to manage dangerous people with severe personality disorder. Tracing subsequent developments, I argue psychological ways of talking, thinking and acting have obtained unparalleled salience in domains of penality and, in turn, radically transformed the conditions of imprisonment. © 2017 Foundation for the Sociology of Health & Illness.

Bioactive Antimicrobial Peptides as Therapeutics for Corneal Wounds and Infections

PubMed Central

Griffith, Gina L.; Kasus-Jacobi, Anne; Pereira, H. Anne

2017-01-01

Significance: More than 2 million eye injuries and infections occur each year in the United States that leave civilians and military members with reduced or complete vision loss due to the lack of effective therapeutics. Severe ocular injuries and infections occur in varied settings including the home, workplace, and battlefields. In this review, we discuss the potential of developing antimicrobial peptides (AMPs) as therapeutics for the treatment of corneal wounds and infections for which the current treatment options are inadequate. Recent Advances: Standard-of-care employs the use of fluorescein dye for the diagnosis of ocular defects and is followed by the use of antibiotics and/or steroids to treat the infection and reduce inflammation. Recent advances for treating corneal wounds include the development of amniotic membrane therapies, wound chambers, and drug-loaded hydrogels. In this review, we will discuss an innovative approach using AMPs with the dual effect of promoting corneal wound healing and clearing infections. Critical Issues: An important aspect of treating ocular injuries is that treatments need to be effective and administered expeditiously. This is especially important for injuries that occur during combat and in individuals who demonstrate delayed wound healing. To overcome gaps in current treatment modalities, bioactive peptides based on naturally occurring cationic antimicrobial proteins are being investigated as new therapeutics. Future Directions: The development of new therapeutics that can treat ocular infections and promote corneal wound healing, including the healing of persistent corneal epithelial defects, would be of great clinical benefit. PMID:28616359

The role of sports and exercise in allergic disease: drawbacks and benefits.

PubMed

Silva, Diana; Moreira, André

2015-01-01

Although training and exercise have several benefits, overdoing it might not necessarily be a good thing. For instance, elite athletes have an increased risk for asthma and allergy. Several mechanisms can be implicated for this risk, which include the interplay between environmental training factors and athlete's personal risk factors, such as genetic susceptibility, neurogenic-mediated inflammation, and epithelial sensitivity. However, an overwhelming amount of scientific evidence shows the positive effects of sports as part of a healthy lifestyle. Training reduces breathlessness and asthma symptoms and attenuates Th2-mediated inflammatory responses. Taken together, the benefits far outweigh the potential hazards of training. An easily administered therapeutic healthy lifestyle intervention, which could be used alongside current treatment, must be developed.

Pomegranate extract and exercise provide additive benefits on improvement of immune function by inhibiting inflammation and oxidative stress in high-fat-diet-induced obesity in rats.

PubMed

Zhao, Fei; Pang, Wentao; Zhang, Ziyi; Zhao, Jialong; Wang, Xin; Liu, Ye; Wang, Xun; Feng, Zhihui; Zhang, Yong; Sun, Wenyan; Liu, Jiankang

2016-06-01

Obesity is reported to be associated with immune dysfunction and a state of low-grade, chronic inflammation. Either pomegranate extract (PomE) or exercise (Ex) has been shown to have antiobesity, anti-inflammatory and antioxidant effects. Nevertheless, no study has addressed the additive benefits of PomE and Ex on the restoration of obesity-induced immune defects. The present work aims to study the effect of PomE and Ex as a combined intervention on immune function and the underlying mechanism involved in inflammation and oxidative stress in rats with high-fat-diet (HFD)-induced obesity. Our results demonstrate that the combination of PomE and Ex showed additive benefits on inhibition of HFD-induced body weight increase and improvement of HFD-induced immune dysfunction, including (a) attenuating the abnormality of histomorphology of the spleen, (b) increasing the ratio of the CD4+:CD8+ T cell subpopulations in splenocytes and peripheral blood mononuclear cells (PBMC), (c) inhibition of apoptosis in splenocytes and PBMC, (d) normalizing peritoneal macrophage phenotypes and (e) restoring immunomodulating factors in serum. We also find that immune dysfunction in HFD-fed rats was associated with increased inflammatory cytokine secretion and oxidative stress biomarkers, and that the combination of PomE and Ex effectively inhibited the inflammatory response and decreased oxidative damage. The effect of PomE and Ex as a combined intervention is greater than the effect of either PomE or Ex alone, showing that PomE and Ex may be additively effective in improving immune function in HFD-fed rats by inhibiting inflammation and decreasing oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

Therapeutic Use of Filgrastim for Established Febrile Neutropenia Is Cost Effective Among Patients With Solid Tumors and Lymphomas.

PubMed

Wang, Xiao Jun; Tong, Wei Xiang; Chan, Alexandre

2017-06-01

With the emergence of biosimilar filgrastim to the market, there is a gradual decrease in the listed price of the originator product of filgrastim over the years, and this could have an impact on the cost-effectiveness of filgrastim in the treatment of febrile neutropenia (FN). A cost-effectiveness analysis would allow clinicians to make informed decision when considering the therapeutic filgrastim among low-risk FN patients. This study aims to evaluate the cost-effectiveness of adding therapeutic filgrastim to antibiotics in the treatment of established FN among patients with solid tumors and lymphomas. A decision tree model was created to compare two treatment options for established FN as follows: (1) antibiotics alone (standard care) and (2) antibiotics with therapeutic filgrastim (comparator). The target population was a hypothetical cohort of adult cancer patients with solid tumors or lymphomas hospitalized with FN in Singapore. The analysis was performed from a hospital's perspective over a 21-day time horizon. The main outcome measures included costs, quality-adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to evaluate the robustness of the results. Compared with antibiotics alone, the treatment strategy of antibiotics with therapeutic filgrastim was a dominant choice, incurring a cost saving of US$125 per patient (comparator versus standard care: US$9110 versus US$9235) and additional health benefit of 0.0007 QALY gained per patient (comparator versus standard care: 0.0450 versus 0.0443). Model results were robust against the parameter variations in the one-way sensitivity analyses, but increasing the cost of filgrastim beyond US$87 per injection would increase the ICER to >US$50,000/QALY. Furthermore, the strategy of antibiotics with therapeutic filgrastim was the preferred choice (dominant or cost-effective) in 83.7% of the model iterations at a

The role of endemic plants in Mauritian traditional medicine - Potential therapeutic benefits or placebo effect?

PubMed

Rummun, Nawraj; Neergheen-Bhujun, Vidushi S; Pynee, Kersley B; Baider, Cláudia; Bahorun, Theeshan

2018-03-01

The Mauritian endemic flora has been recorded to be used as medicines for nearly 300 years. Despite acceptance of these endemic plants among the local population, proper documentation of their therapeutic uses is scarce. This review aims at summarising documented traditional uses of Mauritian endemic species with existing scientific data of their alleged bioactivities, in a view to appeal for more stringent validations for their ethnomedicinal uses. A comprehensive bibliographic investigation was carried out by analysing published books on ethnopharmacology and international peer-reviewed papers via scientific databases namely ScienceDirect and PubMed. The keywords "Mauritius endemic plants" and "Mauritius endemic medicinal plants" were used and articles published from 1980 to 2016 were considered. 675 works of which 12 articles were filtered which documented the ethnomedicinal uses and 22 articles reported the biological activities of Mauritian endemic plants. Only materials published in English or French language were included in the review. Available data on the usage of Mauritian endemic plants in traditional medicine and scientific investigation were related. We documented 87 taxa of Mauritian endemic plants for their medicinal value. Endemic plants are either used as part of complex herbal formulations or singly, and are prescribed by herbalists to mitigate a myriad of diseases from metabolic disorders, dermatological pathologies, arthritis to sexually transmissible diseases. However, these species have undergone a limited consistent evaluation to validate their purported ethnomedicinal claims. As the World Health Organization Traditional Medicine Strategy 2014-2023 emphasises on moving traditional medicine into mainstream medicine on an equally trusted footage, the re-evaluation and modernization of Mauritius cultural heritage become necessary. With a consumer-driven 'return to nature', scientific validation and valorization of the herbal remedies, including

Quantitative Analysis of Therapeutic Drugs in Dried Blood Spot Samples by Paper Spray Mass Spectrometry: An Avenue to Therapeutic Drug Monitoring

NASA Astrophysics Data System (ADS)

Manicke, Nicholas Edward; Abu-Rabie, Paul; Spooner, Neil; Ouyang, Zheng; Cooks, R. Graham

2011-09-01

A method is presented for the direct quantitative analysis of therapeutic drugs from dried blood spot samples by mass spectrometry. The method, paper spray mass spectrometry, generates gas phase ions directly from the blood card paper used to store dried blood samples without the need for complex sample preparation and separation; the entire time for preparation and analysis of blood samples is around 30 s. Limits of detection were investigated for a chemically diverse set of some 15 therapeutic drugs; hydrophobic and weakly basic drugs, such as sunitinib, citalopram, and verapamil, were found to be routinely detectable at approximately 1 ng/mL. Samples were prepared by addition of the drug to whole blood. Drug concentrations were measured quantitatively over several orders of magnitude, with accuracies within 10% of the expected value and relative standard deviation (RSD) of around 10% by prespotting an internal standard solution onto the paper prior to application of the blood sample. We have demonstrated that paper spray mass spectrometry can be used to quantitatively measure drug concentrations over the entire therapeutic range for a wide variety of drugs. The high quality analytical data obtained indicate that the technique may be a viable option for therapeutic drug monitoring.

Engineering of blended nanoparticle platform for delivery of mitochondria-acting therapeutics

PubMed Central

Marrache, Sean; Dhar, Shanta

2012-01-01

Mitochondrial dysfunctions cause numerous human disorders. A platform technology based on biodegradable polymers for carrying bioactive molecules to the mitochondrial matrix could be of enormous potential benefit in treating mitochondrial diseases. Here we report a rationally designed mitochondria-targeted polymeric nanoparticle (NP) system and its optimization for efficient delivery of various mitochondria-acting therapeutics by blending a targeted poly(d,l-lactic-co-glycolic acid)-block (PLGA-b)-poly(ethylene glycol) (PEG)-triphenylphosphonium (TPP) polymer (PLGA-b-PEG-TPP) with either nontargeted PLGA-b-PEG-OH or PLGA-COOH. An optimized formulation was identified through in vitro screening of a library of charge- and size-varied NPs, and mitochondrial uptake was studied by qualitative and quantitative investigations of cytosolic and mitochondrial fractions of cells treated with blended NPs composed of PLGA-b-PEG-TPP and a triblock copolymer containing a fluorescent quantum dot, PLGA-b-PEG-QD. The versatility of this platform was demonstrated by studying various mitochondria-acting therapeutics for different applications, including the mitochondria-targeting chemotherapeutics lonidamine and α-tocopheryl succinate for cancer, the mitochondrial antioxidant curcumin for Alzheimer’s disease, and the mitochondrial uncoupler 2,4-dinitrophenol for obesity. These biomolecules were loaded into blended NPs with high loading efficiencies. Considering efficacy, the targeted PLGA-b-PEG-TPP NP provides a remarkable improvement in the drug therapeutic index for cancer, Alzheimer’s disease, and obesity compared with the nontargeted construct or the therapeutics in their free form. This work represents the potential of a single, programmable NP platform for the diagnosis and targeted delivery of therapeutics for mitochondrial dysfunction-related diseases. PMID:22991470

Advances in refractory ulcerative colitis treatment: A new therapeutic target, Annexin A2

PubMed Central

Tanida, Satoshi; Mizoshita, Tsutomu; Ozeki, Keiji; Katano, Takahito; Kataoka, Hiromi; Kamiya, Takeshi; Joh, Takashi

2015-01-01

Medical treatment has progressed significantly over the past decade towards achieving and maintaining clinical remission in patients with refractory ulcerative colitis (UC). Proposed mediators of inflammation in UC include pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-2, and the cell-surface adhesive molecule integrin α4β7. Conventional therapeutics for active UC include 5-aminosalicylic acid, corticosteroids and purine analogues (azathioprine and 6-mercaptopurine). Patients who fail to respond to conventional therapy are treated with agents such as the calicineurin inhibitors cyclosporine and tacrolimus, the TNF-α inhibitors infliximab or adalimumab, or a neutralizing antibody (vedolizumab) directed against integrin α4β7. These therapeutic agents are of benefit for patients with refractory UC, but are not universally effective. Our recent research on TNF-α shedding demonstrated that inhibition of annexin (ANX) A2 may be a new therapeutic strategy for the prevention of TNF-α shedding during inflammatory bowel disease (IBD) inflammation. In this review, we provide an overview of therapeutic treatments that are effective and currently available for UC patients, as well as some that are likely to be available in the near future. We also propose the potential of ANX A2 as a new molecular target for IBD treatment. PMID:26269667

Engineering responsive supramolecular biomaterials: Toward smart therapeutics.

PubMed

Webber, Matthew J

2016-09-01

Engineering materials using supramolecular principles enables generalizable and modular platforms that have tunable chemical, mechanical, and biological properties. Applying this bottom-up, molecular engineering-based approach to therapeutic design affords unmatched control of emergent properties and functionalities. In preparing responsive materials for biomedical applications, the dynamic character of typical supramolecular interactions facilitates systems that can more rapidly sense and respond to specific stimuli through a fundamental change in material properties or characteristics, as compared to cases where covalent bonds must be overcome. Several supramolecular motifs have been evaluated toward the preparation of "smart" materials capable of sensing and responding to stimuli. Triggers of interest in designing materials for therapeutic use include applied external fields, environmental changes, biological actuators, applied mechanical loading, and modulation of relative binding affinities. In addition, multistimuli-responsive routes can be realized that capture combinations of triggers for increased functionality. In sum, supramolecular engineering offers a highly functional strategy to prepare responsive materials. Future development and refinement of these approaches will improve precision in material formation and responsiveness, seek dynamic reciprocity in interactions with living biological systems, and improve spatiotemporal sensing of disease for better therapeutic deployment.

[Cadavers and mummies as therapeutic means].

PubMed

Massart, D; Sohawon, S; Noordally, O

2010-01-01

Sickness befallen onto him, man found that plant and animal derivatives invigorated him. Thereafter, he found a therapeutic benefit in using man as a means of self cure and especially, dead man from violent death. The foam of the skull of cadaver was an excellent antiepileptic as well as blood coming out from a freshly decapitated man. By applying on diseased parts of his body, so as to get rid of inflammation or infection, cadaver's hands were used against tumors of all kinds. Dead human skin were processed into belts and used therein for helping delivery of parturition women. The mummy must be blackish, foul smelling and hard. Those who were whitish, odorless and powder-like, were unfit for use. Mummy powder applied to the nose would stop nose bleeding. Ambroise Paré (1510-1590) was an adversary of those practices.

Molecular pathology and prostate cancer therapeutics: from biology to bedside.

PubMed

Rodrigues, Daniel Nava; Butler, Lisa M; Estelles, David Lorente; de Bono, Johann S

2014-01-01

Prostate cancer (PCa) is the second most commonly diagnosed malignancy in men and has an extremely heterogeneous clinical behaviour. The vast majority of PCas are hormonally driven diseases in which androgen signalling plays a central role. The realization that castration-resistant prostate cancer (CRPC) continues to rely on androgen signalling prompted the development of new, effective androgen blocking agents. As the understanding of the molecular biology of PCas evolves, it is hoped that stratification of prostate tumours into distinct molecular entities, each with its own set of vulnerabilities, will be a feasible goal. Around half of PCas harbour rearrangements involving a member of the ETS transcription factor family. Tumours without this rearrangement include SPOP mutant as well as SPINK1-over-expressing subtypes. As the number of targeted therapy agents increases, it is crucial to determine which patients will benefit from these interventions and molecular pathology will be key in this respect. In addition to directly targeting cells, therapies that modify the tumour microenvironment have also been successful in prolonging the lives of PCa patients. Understanding the molecular aspects of PCa therapeutics will allow pathologists to provide core recommendations for patient management. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A new amoxicillin/clavulanate therapeutic system: preparation, in vitro and pharmacokinetic evaluation.

PubMed

Kerc, Janez; Opara, Jerneja

2007-04-20

A new peroral amoxicillin/clavulanate therapeutic system composed of immediate release tablet and controlled release floating capsule was developed and evaluated by in vivo bioavailability study. Pharmacokinetic (PK) parameters for amoxicillin and clavulanic acid of the new therapeutic systems: AUCt, AUCi, (AUCt/AUCi), Cmax, Tmax, kel, T(1/2) and additionally for amoxicillin T(4) and T(2) were calculated from the plasma levels. The study confirmed enhanced pharmacokinetic parameters of a newly developed therapeutic system containing 1500 mg of amoxicillin and 125 mg of clavulanic acid. Prolonged time over MIC of amoxicillin in relation to a regular immediate release amoxicillin/clavulanate formulation was confirmed.

Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond

PubMed Central

Gross, Christina; Berry-Kravis, Elizabeth M; Bassell, Gary J

2012-01-01

Fragile X syndrome (FXS) is an inherited neurodevelopmental disease caused by loss of function of the fragile X mental retardation protein (FMRP). In the absence of FMRP, signaling through group 1 metabotropic glutamate receptors is elevated and insensitive to stimulation, which may underlie many of the neurological and neuropsychiatric features of FXS. Treatment of FXS animal models with negative allosteric modulators of these receptors and preliminary clinical trials in human patients support the hypothesis that metabotropic glutamate receptor signaling is a valuable therapeutic target in FXS. However, recent research has also shown that FMRP may regulate diverse aspects of neuronal signaling downstream of several cell surface receptors, suggesting a possible new route to more direct disease-targeted therapies. Here, we summarize promising recent advances in basic research identifying and testing novel therapeutic strategies in FXS models, and evaluate their potential therapeutic benefits. We provide an overview of recent and ongoing clinical trials motivated by some of these findings, and discuss the challenges for both basic science and clinical applications in the continued development of effective disease mechanism-targeted therapies for FXS. PMID:21796106

Potential Benefits of Edible Berries in the Management of Aerodigestive and Gastrointestinal Tract Cancers: Preclinical and Clinical Evidence.

PubMed

Bishayee, Anupam; Haskell, Yennie; Do, Chau; Siveen, Kodappully Sivaraman; Mohandas, Nima; Sethi, Gautam; Stoner, Gary D

2016-07-26

Epidemiological reports as well as experimental studies have demonstrated the significant health benefits provided by regular berry consumption. Berries possess both prophylactic and therapeutic potential against several chronic illnesses, such as cardiovascular, neurodegenerative, and neoplastic diseases. Berries owe their health benefits to phytoconstituents, such as polyphenolic anthocyanins, ellagic acid, and a diverse array of phytochemicals bestowed with potent antioxidant and anti-inflammatory effects as well as the ability to engage a multitude of signaling pathways. This review highlights the principal chemical constituents present in berries and their primary molecular targets. The article presents and critically analyzes the chemopreventive and therapeutic potential of berry extracts, fractions, and bioactive components on various cancers of the gastrointestinal tract (GIT), including esophageal, stomach, intestinal, and colorectal cancers as well as cancers of the upper aerodigestive tract, such as oral cancer. The current status of clinical studies evaluating berry products in several aforementioned cancers is presented. Various emerging issues including dose-ranging and dosage forms, the role of synergy and the usage of combination therapy as well as other relevant areas essential for the development of berry phytoconstituents as mainstream chemopreventive and therapeutic agents against aerodigestive and GIT cancers are critically discussed.

Protein Homeostasis in Amyotrophic Lateral Sclerosis: Therapeutic Opportunities?

PubMed Central

Webster, Christopher P.; Smith, Emma F.; Shaw, Pamela J.; De Vos, Kurt J.

2017-01-01

Protein homeostasis (proteostasis), the correct balance between production and degradation of proteins, is essential for the health and survival of cells. Proteostasis requires an intricate network of protein quality control pathways (the proteostasis network) that work to prevent protein aggregation and maintain proteome health throughout the lifespan of the cell. Collapse of proteostasis has been implicated in the etiology of a number of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), the most common adult onset motor neuron disorder. Here, we review the evidence linking dysfunctional proteostasis to the etiology of ALS and discuss how ALS-associated insults affect the proteostasis network. Finally, we discuss the potential therapeutic benefit of proteostasis network modulation in ALS. PMID:28512398

Written case formulations in the treatment of anorexia nervosa: Evidence for therapeutic benefits.

PubMed

Allen, Karina L; O'Hara, Caitlin B; Bartholdy, Savani; Renwick, Beth; Keyes, Alexandra; Lose, Anna; Kenyon, Martha; DeJong, Hannah; Broadbent, Hannah; Loomes, Rachel; McClelland, Jessica; Serpell, Lucy; Richards, Lorna; Johnson-Sabine, Eric; Boughton, Nicky; Whitehead, Linette; Treasure, Janet; Wade, Tracey; Schmidt, Ulrike

2016-09-01

Case formulation is a core component of many psychotherapies and formulation letters may provide an opportunity to enhance the therapeutic alliance and improve treatment outcomes. This study aimed to determine if formulation letters predict treatment satisfaction, session attendance, and symptom reductions in anorexia nervosa (AN). It was hypothesized that higher quality formulation letters would predict greater treatment satisfaction, a greater number of attended sessions, and greater improvement in eating disorder symptoms. Patients were adult outpatients with AN (n = 46) who received Maudsley Anorexia Nervosa Treatment for Adults (MANTRA) in the context of a clinical trial. A Case Formulation Rating Scheme was used to rate letters for adherence to the MANTRA model and use of a collaborative, reflective, affirming stance. Analyses included linear regression and mixed models. Formulation letters that paid attention to the development of the AN predicted greater treatment acceptability ratings (p = 0.002). More reflective and respectful letters predicted greater reductions in Eating Disorder Examination scores (p = 0.003). Results highlight the potential significance of a particular style of written formulation as part of treatment for AN. Future research should examine applicability to other psychiatric disorders. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:874-882). © 2016 Wiley Periodicals, Inc.

Melatonin as a Pleiotropic Molecule with Therapeutic Potential for Type 2 Diabetes and Cancer.

PubMed

Wojcik, Marzena; Krawczyk, Michal; Wojcik, Pawel; Cypryk, Katarzyna; Wozniak, Lucyna Alicja

2017-11-20

The incidence of both type 2 diabetes (T2DM) and cancer is increasing worldwide, making these diseases a global health problem along with increasing healthcare expenditures. The current therapeutic approaches for treating these multifactorial diseases are far from satisfactory. As increasing evidence shows beneficial effects of melatonin (MLT) on typical pathological changes occurring during the development of T2DM and cancer, the present review focuses on molecular aspects of antidiabetic and anticancer activities of MLT and, moreover, discusses several future directions of research regarding MLT application as potential therapeutic agent. Critical literature analysis in PubMed central combined with personal expertise. Numerous in vitro and in vivo studies have revealed that MLT possesses a number of antidiabetic health benefits by diminishing hyperglycemia, insulin resistance, oxidative stress, and inflammation through modulating various intracellular signaling pathways or other targets involved in the pathophysiology of this disease. Mounting evidence also indicates that MLT exhibits multi-targeted anticancer effects in numerous human malignancies, mainly resulting from its ability to modulate several signal transduction pathways associated with cell survival, proliferation, and apoptosis. Furthermore, beneficial synergistic action of MLT with chemotherapy and radiotherapy has also been observed. Importantly, no adverse outcomes have been found from the clinical use of MLT, which highlights its therapeutic usefulness, either alone or in combination with other conventional therapies, in cancer treatment. The findings described in this review suggest that MLT may confer potential benefits to human health, particularly in respect to T2DM and cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Excess Benefit Plans and Other Nonqualified Deferred Compensation Palns Under ERISA

ERIC Educational Resources Information Center

Vogel, Mark A.

1977-01-01

The benefits of and restrictions imposed on qualified pension and profit-sharing plans are discussed in terms of Excess Benefit Plans (EPB), a type of deferred compensation plan. EPBs and unfunded deferred compensation plans offer flexible methods of providing additional benefits for executives and key employees. (LBH)

Effect of therapeutic class on counseling in community pharmacies.

PubMed

Vainio, Kirsti K; Airaksinen, Marja S A; Hyykky, Tarja T; Enlund, K Hannes

2002-05-01

To assess the effect and importance of the therapeutic class of a drug as a determinant for verbal counseling by community pharmacists. Direct external observations (n = 1431) of pharmacist-customer interactions at the point of delivery of prescription medicines were conducted in 7 community pharmacies in Finland. Trained observers noted whether the pharmacist provided information on directions for use, mode of action, and adverse effects. To examine factors associated with counseling, a multiple logistic regression analysis was constructed, with the dependent variable being counseling of any of the 3 observed topics. In addition to therapeutic class, other independent variables were the pharmacy; pharmacist's age, gender, and degree; and the customer's age, gender, previous use of medicine, and question asking. Provision of counseling differed significantly according to therapeutic classes. Counseling on any of the 3 observed topics was most likely to be provided for customers with antibiotics (80%) and least likely for customers with gynecologic preparations (18%). Differences between therapeutic classes remained statistically significant when the effects of the other variables were controlled for. Other significant predictors for any verbal counseling were the pharmacy, customer's previous use of the medicine, and question asking. Therapeutic class is an important variable that should be included in further studies and considered when comparing studies on patient counseling in community pharmacies.

From Blue to Green: The Development and Implementation of a Therapeutic Horticulture Program for Residents of a Battered Women's Shelter.

PubMed

Renzetti, Claire M; Follingstad, Diane R

2015-01-01

The delivery of therapeutic services to clients is influenced by service providers' understanding of the "fit" of a specific program with their service mandate as well as their perceptions of the potential benefits of the program. This article discusses the development and implementation of a therapeutic horticulture (TH) program at a battered women's shelter that serves 17 counties in Central Kentucky. Through semistructured interviews, we gauge the shelter staff's perceptions of the relationship of the TH program to the shelter's overall mission; their sense of the program's benefits for residents, for the shelter as a community organization, and for themselves; and their concerns about the TH program. We consider how these findings may impact future programming at the shelter, and we discuss plans for further evaluation of the TH program in terms of its impact on shelter residents' long-term outcomes.

Model competencies in regulatory therapeutic product assessment: Health Canada's good review guiding principles as a reviewing community's code of intellectual conduct.

PubMed

Lim, Robyn R

2007-08-01

This article describes some work from the Therapeutic Products Directorate of Health Canada regarding Good Review Practices (GRP). Background information is provided on the Therapeutic Products Directorate (TPD) and its regulatory activities regarding drug and medical device assessment in both the pre- and post-market setting. The TPD Good Review Guiding Principles (GRGP) are described which include a Definition of a Good Therapeutic Product Regulatory Review, Ten Hallmarks of a Good Therapeutic Product Regulatory Review and Ten Precepts. Analysis of the guiding principles discusses possible linkages between the guiding principles and intellectual virtues. Through this analysis an hypothesis is developed that the guiding principles outline a code of intellectual conduct for Health Canada's reviewers of evidence for efficacy, safety, manufacturing quality and benefit-risk regarding therapeutic products. Opportunities to advance therapeutic product regulatory review as a scientific discipline in its own right and to acknowledge that these reviewers constitute a specific community of practice are discussed. Integration of intellectual and ethical approaches across therapeutic product review sectors is also suggested.

Additive Manufacturing: From Form to Function

DTIC Science & Technology

2016-01-01

embedded electronics in clothing that could allow additional protective benefits and health monitoring options.13 AM has also enabled proof-of-concept...the International Space Station (ISS) in September 2014 to test plastics . The second 3D printer was delivered to the ISS in April 2016. In addition...was developed by the Innovative Advanced Concepts program. The sensor is essentially a transparent sheet of plastic with printed elec- tronics that

Hey Factors at the Crossroad of Tumorigenesis and Clinical Therapeutic Modulation of Hey for Anticancer Treatment.

PubMed

Liu, Zihao; Sanders, Andrew J; Liang, Gehao; Song, Erwei; Jiang, Wen G; Gong, Chang

2017-05-01

Hairy and Enhancer-of-split related with YRPW motif (Hey) transcription factors are important regulators of stem cell embryogenesis. Clinical relevance shows that they are also highly expressed in malignant carcinoma. Recent studies have highlighted functions for the Hey factors in tumor metastasis, the maintenance of cancer cell self-renewal, as well as proliferation and the promotion of tumor angiogenesis. Pathways that regulate Hey gene expression, such as Notch and TGFβ signaling, are frequently aberrant in numerous cancers. In addition, Hey factors control downstream targets via recruitment of histone deacetylases (HDAC). Targeting these signaling pathways or HDACs may reverse tumor progression and provide clinical benefit for cancer patients. Thus, some small molecular inhibitors or monoclonal antibodies of each of these signaling pathways have been studied in clinical trials. This review focuses on the involvement of Hey proteins in malignant carcinoma progression and provides valuable therapeutic information for anticancer treatment. Mol Cancer Ther; 16(5); 775-86. ©2017 AACR . ©2017 American Association for Cancer Research.

Conditional rights, benefit reform, and drug users: reducing dependency?

PubMed

Harris, Neville

2010-01-01

United Kingdom government policy to increase social security claimants' entry to the labour market through conditions attached to unemployed, sickness and incapacity benefits now includes additional measures to activate particular groups such as lone parents and drug users. The latter are a prime target because of their high level of dependency on benefits and because social security rules are seen as having the potential to modify the behaviour of individuals with a lifestyle regarded as being at odds with the moral obligations of citizenship and incompatible with the government's realization of its wider economic and social goals. There are strict procedures for the identification of drug-user claimants, enabling additional conditions to be attached to their benefit rights. This article discusses the general trend in benefit reform towards increased conditionality and evaluates the reforms affecting drug users, considering human rights and other implications. It concludes by reflecting on the status of conditional rights to social security as social rights.

Therapeutic drug levels

MedlinePlus

... medlineplus.gov/ency/article/003430.htm Therapeutic drug levels To use the sharing features on this page, please enable JavaScript. Therapeutic drug levels are lab tests to look for the presence ...

Nanobubbles: a promising efficient tool for therapeutic delivery.

PubMed

Cavalli, Roberta; Soster, Marco; Argenziano, Monica

2016-01-01

In recent decades ultrasound-guided delivery of drugs loaded on nanocarriers has been the focus of increasing attention to improve therapeutic treatments. Ultrasound has often been used in combination with microbubbles, micron-sized spherical gas-filled structures stabilized by a shell, to amplify the biophysical effects of the ultrasonic field. Nanometer size bubbles are defined nanobubbles. They were designed to obtain more efficient drug delivery systems. Indeed, their small sizes allow extravasation from blood vessels into surrounding tissues and ultrasound-targeted site-specific release with minimal invasiveness. Additionally, nanobubbles might be endowed with improved stability and longer residence time in systemic circulation. This review will describe the physico-chemical properties of nanobubbles, the formulation parameters and the drug loading approaches, besides potential applications as a therapeutic tool.

Genome Editing in Stem Cells for Disease Therapeutics.

PubMed

Song, Minjung; Ramakrishna, Suresh

2018-04-01

Programmable nucleases including zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindrome repeats (CRISPR)/CRISPR-associated protein have tremendous potential biological and therapeutic applications as novel genome editing tools. These nucleases enable precise modification of the gene of interest by disruption, insertion, or correction. The application of genome editing technology to pluripotent stem cells or hematopoietic stem cells has the potential to remarkably advance the contribution of this technology to life sciences. Specifically, disease models can be generated and effective therapeutics can be developed with great efficiency and speed. Here we review the characteristics and mechanisms of each programmable nuclease. In addition, we review the applications of these nucleases to stem cells for disease therapies and summarize key studies of interest.

THC therapeutic research by independent and state-sponsored investigators: a historical review.

PubMed

Scigliano, J A

1981-01-01

A brief history of the control and use of cannabis in the United States is presented. Essential to the discussion are the federal law: the Marihuana Tax Stamp Act of 1937; the Controlled Substances Act of 1970; and the Federal Food, Drug and Cosmetic Act of 1962. On mandate of Congress in 1968, initial studies were directed to determine effects of long-term use in man. The annual reporting of the status of "Marihuana and Health" was established. In the early 1970s, the scope of research was broadened to include evaluation of THC for use in certain medical conditions. Interest in therapeutic research may have been influenced by anecdotal reports of benefit for nausea and vomiting of cancer chemotherapy and for elevated intraocular pressure of glaucoma, by the lobbying for laws to legalize marihuana by special interest groups, and by the passage of state "Controlled Substances Therapeutic Research" acts (CSTRA). A listing of approved INDs in four therapeutic categories, a chart comparing the components of laws passed by 25 states, and a bibliography of suggested reading for further contact with the subject matter are included.

Lack of Benefit for the Addition of Androgen Deprivation Therapy to Dose-Escalated Radiotherapy in the Treatment of Intermediate- and High-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krauss, Daniel, E-mail: dkrauss@beaumont.edu; Kestin, Larry; Ye, Hong

2011-07-15

Purpose: Assessment of androgen deprivation therapy (ADT) benefits for prostate cancer treated with dose-escalated radiotherapy (RT). Methods and Materials: From 1991 to 2004, 1,044 patients with intermediate- (n = 782) or high-risk (n = 262) prostate cancer were treated with dose-escalated RT at William Beaumont Hospital. Patients received external-beam RT (EBRT) alone, brachytherapy (high or low dose rate), or high dose rate brachytherapy plus pelvic EBRT. Intermediate-risk patients had Gleason score 7, prostate-specific antigen (PSA) 10.0-19.9 ng/mL, or Stage T2b-T2c. High-risk patients had Gleason score 8-10, PSA {>=}20, or Stage T3. Patients were additionally divided specifically by Gleason score, presencemore » of palpable disease, and PSA level to further define subgroups benefitting from ADT. Results: Median follow-up was 5 years; 420 patients received ADT + dose-escalated RT, and 624 received dose-escalated RT alone. For all patients, no advantages in any clinical endpoints at 8 years were associated with ADT administration. No differences in any endpoints were associated with ADT administration based on intermediate- vs. high-risk group or RT modality when analyzed separately. Patients with palpable disease plus Gleason {>=}8 demonstrated improved clinical failure rates and a trend toward improved survival with ADT. Intermediate-risk patients treated with brachytherapy alone had improved biochemical control when ADT was given. Conclusion: Benefits of ADT in the setting of dose-escalated RT remain poorly defined. This question must continue to be addressed in prospective study.« less

Inspiratory and expiratory respiratory muscle training as an adjunct to concurrent strength and endurance training provides no additional 2000 m performance benefits to rowers.

PubMed

Bell, Gordon J; Game, Alex; Jones, Richard; Webster, Travis; Forbes, Scott C; Syrotuik, Dan

2013-01-01

The purpose of this study was to examine respiratory muscle training (RMT) combined with 9 weeks of resistance and endurance training on rowing performance and cardiopulmonary responses. Twenty-seven rowers (mean ± SD: age = 27 ± 9 years; height = 176.9 ± 10.8 cm; and body mass = 76.1 ± 12.6 kg) were randomly assigned to an inspiratory only (n = 13) or expiratory only (n = 14) training group. Both RMT programs were 3 sets of 10 reps, 6 d/wk in addition to an identical 3 d/wk resistance and 3 d/wk endurance training program. Both groups showed similar improvements in 2000 m rowing performance, cardiorespiratory fitness, strength, and maximum inspiratory (PImax) and expiratory (PEmax) pressures (p < .05). It was concluded that there were no additional benefits of 9 weeks of inspiratory or expiratory RMT on simulated 2000 m rowing performance or cardiopulmonary responses when combined with resistance and endurance training in rowers.