Genome-wide association studies in cardiac electrophysiology: recent discoveries and implications for clinical practice.

PubMed

Milan, David J; Lubitz, Steven A; Kääb, Stefan; Ellinor, Patrick T

2010-08-01

Genome-wide association studies have been increasingly used to study the genetics of complex human diseases. Within the field of cardiac electrophysiology, this technique has been applied to conditions such as atrial fibrillation, and several electrocardiographic parameters including the QT interval. While these studies have identified multiple genomic regions associated with each trait, questions remain, including the best way to explore the pathophysiology of each association and the potential for clinical utility. This review will summarize recent genome-wide association study results within cardiac electrophysiology and discuss their broader implications in basic science and clinical medicine. Copyright 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

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.

Pleural effusion leading to right atrial collapse.

PubMed

Khouzam, Rami N; Yusuf, Jawwad

2014-01-01

Rapid accumulation of pericardial fluid can lead to tamponade, resulting in cardiac chambers' collapse, which can lead to hemodynamic and clinical instability, potentially needing emergent pericardiocentesis. Pleural effusion should also be considered as a potential, if rare, cause of cardiac chambers' collapse and possibly cardiac tamponade. This phenomenon has clinical implications because hemodynamically unstable patients with moderate to large pleural effusion may actually need thoracentesis instead of massive volume resuscitation, inotropic agents, or pericardiocentesis. Copyright © 2013 Wiley Periodicals, Inc.

Deeply discounted medications: Implications of generic prescription drug wars.

PubMed

Czechowski, Jessica L; Tjia, Jennifer; Triller, Darren M

2010-01-01

To describe the history of generic prescription pricing programs at major pharmacy chains and their potential implications on prescribing, quality of care, and patient safety. Publicly available generic prescription discount program drug lists as of May 1, 2009. Fierce competition among major pharmacy chains such as Walgreens, CVS, and Walmart has led to a generic prescription pricing war with unclear public health implications. Introduced in 2006, currently 7 of the 10 largest pharmacy chains advertise a version of a deeply discounted medication (DDM) program, accounting for more than 25,000 locations nationally. By early 2008, almost 70 million Americans had used these programs. Although DDM programs lower drug costs for many patients, DDM formularies include potentially ineffective or harmful medications, have the potential to influence physician prescribing behavior, and may impair pharmacists' ability to review complete drug-dispensing records. DDMs are widespread but have the potential for unintended consequences on patients, providers, and the health care system. A systematic review of DDMs needs to evaluate the clinical, economic, and system-level implications of such programs.

Capital planning for clinical integration.

PubMed

Grauman, Daniel M; Neff, Gerald; Johnson, Molly Martha

2011-04-01

When assessing the financial implications of a physician alignment and clinical integration initiative, a hospital should measure the initiative's potential ROI, perhaps best using a combination of net present value and payback period. The hospital should compare its own historical and projected performance with rating agency median benchmarks for key financial indicators of profitability, debt service, capital and cash flow, and liquidity. The hospital should also consider potential indirect benefits, such as retained outpatient/ancillary revenue, increased inpatient revenue, improved cost control, and improved quality and reporting transparency.

Long non-coding RNAs in hepatocellular carcinoma: Potential roles and clinical implications

PubMed Central

Niu, Zhao-Shan; Niu, Xiao-Jun; Wang, Wen-Hong

2017-01-01

Long non-coding RNAs (lncRNAs) are a subgroup of non-coding RNA transcripts greater than 200 nucleotides in length with little or no protein-coding potential. Emerging evidence indicates that lncRNAs may play important regulatory roles in the pathogenesis and progression of human cancers, including hepatocellular carcinoma (HCC). Certain lncRNAs may be used as diagnostic or prognostic markers for HCC, a serious malignancy with increasing morbidity and high mortality rates worldwide. Therefore, elucidating the functional roles of lncRNAs in tumors can contribute to a better understanding of the molecular mechanisms of HCC and may help in developing novel therapeutic targets. In this review, we summarize the recent progress regarding the functional roles of lncRNAs in HCC and explore their clinical implications as diagnostic or prognostic biomarkers and molecular therapeutic targets for HCC. PMID:28932078

Rivastigmine for Alzheimer's disease: Canadian interpretation of intermediate outcome measures and cost implications.

PubMed

Baladi, J F; Bailey, P A; Black, S; Bouchard, R W; Farcnik, K D; Gauthier, S; Kertesz, A; Mohr, E; Robillard, A

2000-12-01

Clinical studies have shown that patients with Alzheimer's disease (AD) who are treated with rivastigmine have statistically significantly better scores on 5 scales used to assess AD than control patients receiving placebo. However, the clinical meaning and cost implications of these differences are not clear. The purpose of this study was to assess the clinical meaning and cost implications of statistically significant results obtained in clinical trials of rivastigmine for the treatment of AD. Potential cost implications for the health care system, caregivers, and society are considered. Data on clinical effects of rivastigmine were obtained from published North American and European clinical studies of patients with mild to moderately severe AD receiving rivastigmine 6 to 12 mg/d (n = 828) or placebo (n = 647). Differences in scores on the Alzheimer's Disease Assessment Scale-Cognitive Function, Clinician's Interview-Based Impression of Change with both clinical and caregiver information considered, Progressive Deterioration Scale, Mini-Mental State Examination (MMSE), and Global Deterioration Scale were assessed. A convenience panel of 9 Canadian specialists experienced in the treatment of AD provided their opinions on the clinical importance of the trial results. Chart review was performed to identify specific behaviors that improved, and cost implications of improvements were assessed. The panel determined that statistically significant differences in scores on all scales except the MMSE were likely associated with functional or cognitive differences that were clinically relevant for patients, reflecting stabilization that would have beneficial consequences for caregivers and health care resource use. Subsequent chart review showed that improvement on specific scale items confirmed the physician panel's opinion. Analysis of possible cost implications to society indicated that medication expenditures would be offset largely by delays in the need for paid home care and institutionalization, positive effects on caregiver health, and less time lost from work for the caregiver. From the perspective of a Canadian specialist panel, rivastigmine treatment for AD produces clinically relevant effects for patients that are beneficial to caregivers. These effects suggest decreased use of caregiver resources and delays in the need for institutionalization, both of which reduce societal costs.

Neuropeptides in tendinopathy

PubMed Central

Scott, Alexander; Bahr, Roald

2014-01-01

Tendinopathy is a clinical syndrome of pain, tendon thickening, and increased blood flow. The current review highlights evidence supporting an underlying role of neuropeptides in the etiology, clinical presentation, and treatment of painful overuse tendinopathy. Painful tendons demonstrate an increased presence of Substance P-containing nerves which are strongly implicated as a potential source of pain, but which also play important roles in the tendon’s attempt to self-repair. Recent findings have identified potential roles of additional sensory and autonomic neuropeptides which regulate pain, tissue remodeling, and vascular flow, including acetylcholine, noradrenaline and neuropeptide Y. Neuropeptide production within tendons is stimulated by mechanical load and exercise, and both direct and indirect neuropeptide effects may be responsible for the potential benefits of heavy-load eccentric loading. A model is presented which delineates the physiologic basis for signalling pathways between tenocytes, mast cells and sensory and autonomic nerves, with implications for understanding the mechanisms of traditional as well as emerging treatment strategies including sclerosing therapy and nitric oxide. PMID:19273194

Engineered BDNF producing cells as a potential treatment for neurologic disease

PubMed Central

Deng, Peter; Anderson, Johnathon D.; Yu, Abigail S.; Annett, Geralyn; Fink, Kyle D.; Nolta, Jan A.

2018-01-01

Introduction Brain-derived neurotrophic factor (BDNF) has been implicated in wide range of neurological diseases and injury. This neurotrophic factor is vital for neuronal health, survival, and synaptic connectivity. Many therapies focus on the restoration or enhancement of BDNF following injury or disease progression. Areas covered The present review will focus on the mechanisms in which BDNF exerts its beneficial functioning, current BDNF therapies, issues and potential solutions for delivery of neurotrophic factors to the central nervous system, and other disease indications that may benefit from overexpression or restoration of BDNF. Expert opinion Due to the role of BDNF in neuronal development, maturation, and health, BDNF is implicated in numerous neurological diseases making it a prime therapeutic agent. Numerous studies have shown the therapeutic potential of BDNF in a number of neurodegenerative disease models and in acute CNS injury, however clinical translation has fallen short due to issues in delivering this molecule. The use of MSC as a delivery platform for BDNF holds great promise for clinical advancement of neurotrophic factor restoration. The ease with which MSC can be engineered opens the door to the possibility of using this cell-based delivery system to advance a BDNF therapy to the clinic. PMID:27159050

Wikipedia use: Risk for developing technology addiction.

PubMed

Sharma, Manoj Kumar

2016-01-01

The present case highlights the addictive potential of Wikipedia usage. The users approached a technology addiction clinic for the management of excessive use of technology. A clinical interview was used to elicit information about usages. It indicates the addictive use of Wikipedia and associated dysfunction in lifestyle. It has implication for promotion of healthy use of technology.

Hormetic Response to Low-Dose Radiation: Focus on the Immune System and Its Clinical Implications

PubMed Central

Cui, Jiuwei; Yang, Guozi; Pan, Zhenyu; Zhao, Yuguang; Liang, Xinyue; Li, Wei; Cai, Lu

2017-01-01

The interrelationship between ionizing radiation and the immune system is complex, multifactorial, and dependent on radiation dose/quality and immune cell type. High-dose radiation usually results in immune suppression. On the contrary, low-dose radiation (LDR) modulates a variety of immune responses that have exhibited the properties of immune hormesis. Although the underlying molecular mechanism is not fully understood yet, LDR has been used clinically for the treatment of autoimmune diseases and malignant tumors. These advancements in preclinical and clinical studies suggest that LDR-mediated immune modulation is a well-orchestrated phenomenon with clinical potential. We summarize recent developments in the understanding of LDR-mediated immune modulation, with an emphasis on its potential clinical applications. PMID:28134809

Depression at an Early Age.

ERIC Educational Resources Information Center

Alper, Joseph

1986-01-01

Addresses the crisis associated with adolescent affective disorders and probes potential genetics, environmental, and physiological factors. Reviews case examples of depression, eating disorders, and suicide among youths. States clinical implications and advocates early diagnosis and treatment. (ML)

Applying a Cognitive Neuroscience Perspective to Disruptive Behavior Disorders: Implications for Schools.

PubMed

Tyler, Patrick M; White, Stuart F; Thompson, Ronald W; Blair, R J R

2018-02-12

A cognitive neuroscience perspective seeks to understand behavior, in this case disruptive behavior disorders (DBD), in terms of dysfunction in cognitive processes underpinned by neural processes. While this type of approach has clear implications for clinical mental health practice, it also has implications for school-based assessment and intervention with children and adolescents who have disruptive behavior and aggression. This review articulates a cognitive neuroscience account of DBD by discussing the neurocognitive dysfunction related to emotional empathy, threat sensitivity, reinforcement-based decision-making, and response inhibition. The potential implications for current and future classroom-based assessments and interventions for students with these deficits are discussed.

Should dentistry be part of the National Health Information Infrastructure?

PubMed

Schleyer, Titus K L

2004-12-01

The National Health Information Infrastructure, or NHII, proposes to improve the effectiveness, efficiency and overall quality of health in the United States by establishing a national, electronic information network for health care. To date, dentistry's integration into this network has not been discussed widely. The author reviews the NHII and its goals and structure through published reports and background literature. The author evaluates the advantages and disadvantages of the NHII regarding their implications for the dental care system. The NHII proposes to implement computer-based patient records, or CPRs, for most Americans by 2014, connect personal health information with other clinical and public health information, and enable different types of care providers to access CPRs. Advantages of the NHII include transparency of health information across health care providers, potentially increased involvement of patients in their care, better clinical decision making through connecting patient-specific information with the best clinical evidence, increased efficiency, enhanced bioterrorism defense and potential cost savings. Challenges in the implementation of the NHII in dentistry include limited use of CPRs, required investments in information technology, limited availability and adoption of standards, and perceived threats to privacy and confidentiality. The implementation of the NHII is making rapid strides. Dentistry should become an active participant in the NHII and work to ensure that the needs of dental patients and the profession are met. Practice Implications. The NHII has far-reaching implications on dental practice by making it easier to access relevant patient information and by helping to improve clinical decision making.

LncRNAs: the bridge linking RNA and colorectal cancer

PubMed Central

Yang, Qilian; Le, Xiaobing; Yang, Huiliang; Wang, Chenlu; Luo, Zhongyue; Xuan, Yu; Chen, Yi; Deng, Xiangbing; Xu, Lian; Feng, Min; Yi, Tao; Zhao, Xia; Zhou, Shengtao

2017-01-01

Long noncoding RNAs (lncRNAs) are transcribed by genomic regions (exceeding 200 nucleotides in length) that do not encode proteins. While the exquisite regulation of lncRNA transcription can provide signals of malignant transformation, lncRNAs control pleiotropic cancer phenotypes through interactions with other cellular molecules including DNA, protein, and RNA. Recent studies have demonstrated that dysregulation of lncRNAs is influential in proliferation, angiogenesis, metastasis, invasion, apoptosis, stemness, and genome instability in colorectal cancer (CRC), with consequent clinical implications. In this review, we explicate the roles of different lncRNAs in CRC, and the potential implications for their clinical application. PMID:27888635

Clarifying assumptions to enhance our understanding and assessment of clinical reasoning.

PubMed

Durning, Steven J; Artino, Anthony R; Schuwirth, Lambert; van der Vleuten, Cees

2013-04-01

Deciding on a diagnosis and treatment is essential to the practice of medicine. Developing competence in these clinical reasoning processes, commonly referred to as diagnostic and therapeutic reasoning, respectively, is required for physician success. Clinical reasoning has been a topic of research for several decades, and much has been learned. However, there still exists no clear consensus regarding what clinical reasoning entails, let alone how it might best be taught, how it should be assessed, and the research and practice implications therein.In this article, the authors first discuss two contrasting epistemological views of clinical reasoning and related conceptual frameworks. They then outline four different theoretical frameworks held by medical educators that the authors believe guide educators' views on the topic, knowingly or not. Within each theoretical framework, the authors begin with a definition of clinical reasoning (from that viewpoint) and then discuss learning, assessment, and research implications. The authors believe these epistemologies and four theoretical frameworks also apply to other concepts (or "competencies") in medical education.The authors also maintain that clinical reasoning encompasses the mental processes and behaviors that are shared (or evolve) between the patient, physician, and the environment (i.e., practice setting). Clinical reasoning thus incorporates components of all three factors (patient, physician, environment). The authors conclude by outlining practical implications and potential future areas for research.

Increased Neurotropic Threat from Burkholderia pseudomallei Strains with a B. mallei–like Variation in the bimA Motility Gene, Australia

PubMed Central

Fane, Anne; Sarovich, Derek S.; Price, Erin P.; Rush, Catherine M.; Govan, Brenda L.; Parker, Elizabeth; Mayo, Mark; Currie, Bart J.; Ketheesan, Natkunam

2017-01-01

Neurologic melioidosis is a serious, potentially fatal form of Burkholderia pseudomallei infection. Recently, we reported that a subset of clinical isolates of B. pseudomallei from Australia have heightened virulence and potential for dissemination to the central nervous system. In this study, we demonstrate that this subset has a B. mallei–like sequence variation of the actin-based motility gene, bimA. Compared with B. pseudomallei isolates having typical bimA alleles, isolates that contain the B. mallei–like variation demonstrate increased persistence in phagocytic cells and increased virulence with rapid systemic dissemination and replication within multiple tissues, including the brain and spinal cord, in an experimental model. These findings highlight the implications of bimA variation on disease progression of B. pseudomallei infection and have considerable clinical and public health implications with respect to the degree of neurotropic threat posed to human health. PMID:28418830

www.mydrugdealer.com: Ethics and legal implications of Internet-based access to substances of abuse.

PubMed

Klein, Carolina A; Kandel, Surendra

2011-01-01

The Internet has increasingly become an intrinsic part of everyday life, offering countless possibilities for education, services, recreation, and more. In fact, an entire virtual life within the digitalized World Wide Web is possible and common among many Internet users. Today's psychiatrists must therefore incorporate this dimension of human life into clinical practice, to achieve an adequate assessment of the tools and risks available to the patient. We focus on the Internet as a portal for the trade of and access to substances of abuse. We review the legal regulations that may inform care and standards of practice and analyze the difficulties that arise in assessment and monitoring of the current situation. We consider the potential impact of Internet-based narcotics trade on addiction morbidities and the practice of clinical psychiatry, as well as on the potential legal implications that the forensic expert may face.

Increased Neurotropic Threat from Burkholderia pseudomallei Strains with a B. mallei-like Variation in the bimA Motility Gene, Australia.

PubMed

Morris, Jodie L; Fane, Anne; Sarovich, Derek S; Price, Erin P; Rush, Catherine M; Govan, Brenda L; Parker, Elizabeth; Mayo, Mark; Currie, Bart J; Ketheesan, Natkunam

2017-05-01

Neurologic melioidosis is a serious, potentially fatal form of Burkholderia pseudomallei infection. Recently, we reported that a subset of clinical isolates of B. pseudomallei from Australia have heightened virulence and potential for dissemination to the central nervous system. In this study, we demonstrate that this subset has a B. mallei-like sequence variation of the actin-based motility gene, bimA. Compared with B. pseudomallei isolates having typical bimA alleles, isolates that contain the B. mallei-like variation demonstrate increased persistence in phagocytic cells and increased virulence with rapid systemic dissemination and replication within multiple tissues, including the brain and spinal cord, in an experimental model. These findings highlight the implications of bimA variation on disease progression of B. pseudomallei infection and have considerable clinical and public health implications with respect to the degree of neurotropic threat posed to human health.

Clarity and strength of implications for practice in medical journal articles: an exploratory analysis

PubMed Central

Owens, Allessia P; Bartunek, Jean M

2011-01-01

Objective To examine how leading clinical journals report research findings, aiming to assess how they frame their implications for medical practice and to compare that literature's patterns with those of the management literature. Data Source Clinically relevant research articles from three leading clinical journals (N Engl J Med, JAMA, and Ann Intern Med). Methods Review of wording of a sequential sample from 2010, with categorisation, comparison among journals, and comparison with management literature. Results Clinical journals usually state that one approach did or did not differ from another approach (35 of 51 articles, 68.6%), but they recommended a specific course of action (‘therefore, x should be done’) in just 25.5%. One article gave instruction on how to implement the changes. Two-thirds of the reports called for further research. Half used tentative language. Management research articles nearly always specified who should use the information and drew from over 60 types of potential users, whereas the clinical literature named the audience in only 23.5% of clinicians. Conclusions Authors and editors of the clinical literature could test being more clear and direct in presenting implications of research findings for practice, including stating when the findings do not justify changes in practice. PMID:21450773

Intra-tumor heterogeneity: lessons from microbial evolution and clinical implications

PubMed Central

2013-01-01

Multiple subclonal populations of tumor cells can coexist within the same tumor. This intra-tumor heterogeneity will have clinical implications and it is therefore important to identify factors that drive or suppress such heterogeneous tumor progression. Evolutionary biology can provide important insights into this process. In particular, experimental evolution studies of microbial populations, which exist as clonal populations that can diversify into multiple subclones, have revealed important evolutionary processes driving heterogeneity within a population. There are transferrable lessons that can be learnt from these studies that will help us to understand the process of intra-tumor heterogeneity in the clinical setting. In this review, we summarize drivers of microbial diversity that have been identified, such as mutation rate and environmental influences, and discuss how knowledge gained from microbial experimental evolution studies may guide us to identify and understand important selective factors that promote intra-tumor heterogeneity. Furthermore, we discuss how these factors could be used to direct and optimize research efforts to improve patient care, focusing on therapeutic resistance. Finally, we emphasize the need for longitudinal studies to address the impact of these potential tumor heterogeneity-promoting factors on drug resistance, metastatic potential and clinical outcome. PMID:24267946

Exploring policy makers' perspectives on a clinical controversy: airway surgery for adult obstructive sleep apnoea.

PubMed

Elshaug, A G; Hiller, J E; Moss, J R

2009-10-01

Worldwide, there is increasing focus on measures to reduce ineffective healthcare practices. Upper airway surgeries for the treatment of adult obstructive sleep apnoea (OSA) represent a case-study in this area, given recent publications that draw into question their efficacy. Policy stakeholders were canvassed to assess their perspectives on this. Senior health policy stakeholders from Australia were criterion and snowball sampled (to identify opinion leaders). Participants were presented with preparatory material and took part in individual semistructured interviews. These focused on eliciting responses to recently published evidence and a relevant Cochrane review. Questions were posed relating to clinical effectiveness and associated policy implications. Interviews were taped and transcribed for thematic analysis. Participant comments were de-identified. Ten stakeholders were interviewed before saturation was reached. Thematic analysis highlighted participant concern with the diversity of procedures on offer, coupled with limited effectiveness (suggesting potential clinical uncertainty) and considerations therefore of resource allocation (potential opportunity cost). Stakeholders seem aware of the methodological complexities, the ethical issues raised and the role of patients in considerations regarding appropriateness. Finally, policy stakeholders acknowledge that these procedures appear appropriate only for a minority, with consensus that policy level restrictions to government funding for these procedures may be warranted. This report highlights that this clinical controversy is of interest and relevance from a policy perspective with lessons and potential implications for clinical practice. It further highlights the need for clinical consensus on definitions of surgical "success" in treating this condition, as this forms an important pretext to policy considerations.

Structural properties of fracture haematoma: current status and future clinical implications.

PubMed

Wang, Xin; Friis, Thor; Glatt, Vaida; Crawford, Ross; Xiao, Yin

2017-10-01

Blood clots (haematomas) that form immediately following a bone fracture have been shown to be vital for the subsequent healing process. During the clotting process, a number of factors can influence the fibrin clot structure, such as fibrin polymerization, growth factor binding, cellular infiltration (including platelet retraction), protein concentrations and cytokines. The modulation of the fibrin clot structure within the fracture site has important clinical implications and could result in the development of multifunctional scaffolds that mimic the natural structure of a haematoma. Artificial haematoma structures such as these can be created from the patient's own blood and can therefore act as an ideal bone defect filling material for potential clinical application to accelerate bone regeneration. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Is pedophilia a sexual orientation?

PubMed

Seto, Michael C

2012-02-01

In this article, I address the question of whether pedophilia in men can be construed as a male sexual orientation, and the implications for thinking of it in this way for scientific research, clinical practice, and public policy. I begin by defining pedophilia and sexual orientation, and then compare pedophilia (as a potential sexual orientation with regard to age) to sexual orientations with regard to gender (heterosexuality, bisexuality, and homosexuality), on the bases of age of onset, correlations with sexual and romantic behavior, and stability over time. I conclude with comments about the potential social and legal implications of conceptualizing pedophilia as a type of sexual orientation in males.

Social Cognition Dysfunctions in Neurodegenerative Diseases: Neuroanatomical Correlates and Clinical Implications.

PubMed

Christidi, Foteini; Migliaccio, Raffaella; Santamaría-García, Hernando; Santangelo, Gabriella; Trojsi, Francesca

2018-01-01

Social cognitive function, involved in the perception, processing, and interpretation of social information, has been shown to be crucial for successful communication and interpersonal relationships, thereby significantly impacting mental health, well-being, and quality of life. In this regard, assessment of social cognition, mainly focusing on four key domains, such as theory of mind (ToM), emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. With regard to neurodegenerative diseases (NDs), most disorders, characterized by variable disease phenotypes and progression, although similar for the unfavorable prognosis, are associated to impairments of social cognitive function, with consequent negative effects on patients' management. Specifically, in some NDs these deficits may represent core diagnostic criteria, such as for behavioral variant frontotemporal dementia (bvFTD), or may emerge during the disease course as critical aspects, such as for Parkinson's and Alzheimer's diseases. On this background, we aimed to revise the most updated evidence on the neurobiological hypotheses derived from network-based approaches, clinical manifestations, and assessment tools of social cognitive dysfunctions in NDs, also prospecting potential benefits on patients' well-being, quality of life, and outcome derived from potential therapeutic perspectives of these deficits.

Genomics and infectious disease: a call to identify the ethical, legal and social implications for public health and clinical practice.

PubMed

Geller, Gail; Dvoskin, Rachel; Thio, Chloe L; Duggal, Priya; Lewis, Michelle H; Bailey, Theodore C; Sutherland, Andrea; Salmon, Daniel A; Kahn, Jeffrey P

2014-01-01

Advances in genomics are contributing to the development of more effective, personalized approaches to the prevention and treatment of infectious diseases. Genetic sequencing technologies are furthering our understanding of how human and pathogen genomic factors - and their interactions - contribute to individual differences in immunologic responses to vaccines, infections and drug therapies. Such understanding will influence future policies and procedures for infectious disease management. With the potential for tailored interventions for particular individuals, populations or subpopulations, ethical, legal and social implications (ELSIs) may arise for public health and clinical practice. Potential considerations include balancing health-related benefits and harms between individuals and the larger community, minimizing threats to individual privacy and autonomy, and ensuring just distribution of scarce resources. In this Opinion, we consider the potential application of pathogen and host genomic information to particular viral infections that have large-scale public health consequences but differ in ELSI-relevant characteristics such as ease of transmission, chronicity, severity, preventability and treatability. We argue for the importance of anticipating these ELSI issues in advance of new scientific discoveries, and call for the development of strategies for identifying and exploring ethical questions that should be considered as clinical, public health and policy decisions are made.

Suppressing iron oxide nanoparticle toxicity by vascular targeted antioxidant polymer nanoparticles.

PubMed

Cochran, David B; Wattamwar, Paritosh P; Wydra, Robert; Hilt, J Zach; Anderson, Kimberly W; Eitel, Richard E; Dziubla, Thomas D

2013-12-01

The biomedical use of superparamagnetic iron oxide nanoparticles has been of continued interest in the literature and clinic. Their ability to be used as contrast agents for imaging and/or responsive agents for remote actuation makes them exciting materials for a wide range of clinical applications. Recently, however, concern has arisen regarding the potential health effects of these particles. Iron oxide toxicity has been demonstrated in in vivo and in vitro models, with oxidative stress being implicated as playing a key role in this pathology. One of the key cell types implicated in this injury is the vascular endothelial cells. Here, we report on the development of a targeted polymeric antioxidant, poly(trolox ester), nanoparticle that can suppress oxidative damage. As the polymer undergoes enzymatic hydrolysis, active trolox is locally released, providing a long term protection against pro-oxidant agents. In this work, poly(trolox) nanoparticles are targeted to platelet endothelial cell adhesion molecules (PECAM-1), which are able to bind to and internalize in endothelial cells and provide localized protection against the cytotoxicity caused by iron oxide nanoparticles. These results indicate the potential of using poly(trolox ester) as a means of mitigating iron oxide toxicity, potentially expanding the clinical use and relevance of these exciting systems. Copyright © 2013 Elsevier Ltd. All rights reserved.

Social Cognition Dysfunctions in Neurodegenerative Diseases: Neuroanatomical Correlates and Clinical Implications

PubMed Central

Santamaría-García, Hernando; Santangelo, Gabriella

2018-01-01

Social cognitive function, involved in the perception, processing, and interpretation of social information, has been shown to be crucial for successful communication and interpersonal relationships, thereby significantly impacting mental health, well-being, and quality of life. In this regard, assessment of social cognition, mainly focusing on four key domains, such as theory of mind (ToM), emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. With regard to neurodegenerative diseases (NDs), most disorders, characterized by variable disease phenotypes and progression, although similar for the unfavorable prognosis, are associated to impairments of social cognitive function, with consequent negative effects on patients' management. Specifically, in some NDs these deficits may represent core diagnostic criteria, such as for behavioral variant frontotemporal dementia (bvFTD), or may emerge during the disease course as critical aspects, such as for Parkinson's and Alzheimer's diseases. On this background, we aimed to revise the most updated evidence on the neurobiological hypotheses derived from network-based approaches, clinical manifestations, and assessment tools of social cognitive dysfunctions in NDs, also prospecting potential benefits on patients' well-being, quality of life, and outcome derived from potential therapeutic perspectives of these deficits. PMID:29854017

Mismatch Negativity and P3a in Adolescents and Young Adults with Autism Spectrum Disorders: Behavioral Correlates and Clinical Implications

ERIC Educational Resources Information Center

Chien, Yi-Ling; Hsieh, Ming Hsien; Gau, Susan Shur-Fen

2018-01-01

In a sample of 37 adolescents and young adults with autism spectrum disorder (ASD) and 35 typically-developing controls (TDC), we investigated sensory symptoms by clinical measures, and Mismatch Negativity and P3a component at Fz with the frequency and duration oddball paradigms of event-related potentials. Results showed that compared to TDC, ASD…

Statistical reporting of clinical pharmacology research.

PubMed

Ring, Arne; Schall, Robert; Loke, Yoon K; Day, Simon

2017-06-01

Research in clinical pharmacology covers a wide range of experiments, trials and investigations: clinical trials, systematic reviews and meta-analyses of drug usage after market approval, the investigation of pharmacokinetic-pharmacodynamic relationships, the search for mechanisms of action or for potential signals for efficacy and safety using biomarkers. Often these investigations are exploratory in nature, which has implications for the way the data should be analysed and presented. Here we summarize some of the statistical issues that are of particular importance in clinical pharmacology research. © 2017 The British Pharmacological Society.

Morphological and clinical aspects of the occurrence of accessory (multiple) renal arteries

PubMed Central

Gulas, Ewelina; Wysiadecki, Grzegorz; Szymański, Jacek; Majos, Agata; Stefańczyk, Ludomir; Topol, Mirosław

2016-01-01

Renal vascularization variants vastly differ between individuals due to the very complex embryogenesis of the kidneys. Moreover, each variant may have implications for clinical and surgical interventions. The number of operating procedures continues to grow, and includes renal transplants, aneurysmorrhaphy and other vascular reconstructions. In any surgical technique, unawareness of the presence of multiple renal arteries may result in a fatal outcome, especially if laparoscopic methods are used. The aim of this review is to comprehensively identify the variation within multiple renal arteries and to highlight the connections between the presence of accessory renal arteries and the coexistence of other variants of vascularization. Another aim is to determine the potential clinical implications of the presence of accessory renal arteries. This study is of particular importance for surgeons, intervention radiologists, nephrologists and vascular surgeons. PMID:29593819

Proprioception: where are we now? A commentary on clinical assessment, changes across the life course, functional implications and future interventions.

PubMed

Suetterlin, Karen Joan; Sayer, Avan Aihie

2014-05-01

Proprioception, the sense of where one is in space, is essential for effective interaction with the environment. A lack of or reduction in proprioceptive acuity has been directly correlated with falls and with reduced functional independence in older people. Proprioceptive losses have also been shown to negatively correlate with functional recovery post stroke and play a significant role in other conditions such as Parkinson's disease. However, despite its central importance to many geriatric syndromes, the clinical assessment of proprioception has remained remarkably static. We look at approaches to the clinical assessment of proprioception, changes in proprioception across the life course, functional implications of proprioception in health and disease and the potential for targeted interventions in the future such as joint taping, and proprioception-specific rehabilitation and footwear.

Li-Fraumeni syndrome: cancer risk assessment and clinical management.

PubMed

McBride, Kate A; Ballinger, Mandy L; Killick, Emma; Kirk, Judy; Tattersall, Martin H N; Eeles, Rosalind A; Thomas, David M; Mitchell, Gillian

2014-05-01

Carriers of germline mutations in the TP53 gene, encoding the cell-cycle regulator and tumour suppressor p53, have a markedly increased risk of cancer-related morbidity and mortality during both childhood and adulthood, and thus require appropriate and effective cancer risk management. However, the predisposition of such patients to multiorgan tumorigenesis presents a specific challenge for cancer risk management programmes. Herein, we review the clinical implications of germline mutations in TP53 and the evidence for cancer screening and prevention strategies in individuals carrying such mutations, as well as examining the potential psychosocial implications of lifelong management for a ubiquitous cancer risk. In addition, we propose an evidence-based framework for the clinical management of TP53 mutation carriers and provide a platform for addressing the management of other cancer predisposition syndromes that can affect multiple organs.

Hearing and Cognitive Impairment and the Role of the International Classification of Functioning, Disability and Health as a Rehabilitation Framework

PubMed Central

Lind, Christopher; Meyer, Carly; Young, Jessica

2016-01-01

The International Classification of Functioning, Disability and Health (ICF) has been applied widely in the literature to describe and differentiate the broad implications of hearing impairment (HI) and cognitive impairment (CI) on communication. As CI and HI are largely age-related conditions, the likelihood of comorbidity of these conditions is high. In the context of an aging population, the prevalence of comorbidity is likely to rise, yet much of the clinical assessment and intervention in HI and CI occur separately. The benefit of addressing the dual impact of these conditions is of increasing clinical importance for all clinicians working with older adults and for audiologists and speech pathologists in particular. In this article, the ICF model will be applied to explore the everyday implications of HI and CI. Furthermore, the clinical implications of the ICF model are explored with particular respect to communication assessment and intervention options. The potential benefit of combining activity- and participation-focused interventions currently offered for HI and CI independently is examined. PMID:27489399

Essential Genetic and Genomic Nursing Competencies for the Oncology Nurse

PubMed Central

Jenkins, Jean

2010-01-01

Objectives To review the opportunities and possibilities for advancing oncology nursing competencies in genetic/genomics through the illustration of case scenarios in clinical care. Data Sources Literature; research reports. Conclusions Oncology nurses have the potential to influence whether or not cutting edge research discoveries are utilized at the bedside. Clinical integration of genetic/genomic information has the potential to optimize health outcomes and lengthen patient lives. Implications for Nursing Practice Oncology nurses need to include genetics/genomics in their practice in order to impact quality patient care today and for the future. PMID:21255714

Considerations for using data envelopment analysis for the assessment of radiotherapy treatment plan quality.

PubMed

Simpson, John; Raith, Andrea; Rouse, Paul; Ehrgott, Matthias

2017-10-09

Purpose The operations research method of data envelopment analysis (DEA) shows promise for assessing radiotherapy treatment plan quality. The purpose of this paper is to consider the technical requirements for using DEA for plan assessment. Design/methodology/approach In total, 41 prostate treatment plans were retrospectively analysed using the DEA method. The authors investigate the impact of DEA weight restrictions with reference to the ability to differentiate plan performance at a level of clinical significance. Patient geometry influences plan quality and the authors compare differing approaches for managing patient geometry within the DEA method. Findings The input-oriented DEA method is the method of choice when performing plan analysis using the key undesirable plan metrics as the DEA inputs. When considering multiple inputs, it is necessary to constrain the DEA input weights in order to identify potential plan improvements at a level of clinical significance. All tested approaches for the consideration of patient geometry yielded consistent results. Research limitations/implications This work is based on prostate plans and individual recommendations would therefore need to be validated for other treatment sites. Notwithstanding, the method that requires both optimised DEA weights according to clinical significance and appropriate accounting for patient geometric factors is universally applicable. Practical implications DEA can potentially be used during treatment plan development to guide the planning process or alternatively used retrospectively for treatment plan quality audit. Social implications DEA is independent of the planning system platform and therefore has the potential to be used for multi-institutional quality audit. Originality/value To the authors' knowledge, this is the first published examination of the optimal approach in the use of DEA for radiotherapy treatment plan assessment.

Dependence and caring in clinical communication: The relevance of attachment and other theories

PubMed Central

Salmon, Peter; Young, Bridget

2009-01-01

Objective Clinical relationships are usually asymmetric, being defined by patients’ dependence and practitioners’ care. Our aims are to: (i) identify literature that can contribute to theory for researching and teaching clinical communication from this perspective; (ii) highlight where theoretical development is needed; and (iii) test the utility of the emerging theory by identifying whether it leads to implications for educational practice. Methods Selective and critical review of research concerned with dependence and caring in clinical and non-clinical relationships. Results Attachment theory helps to understand patients’ need to seek safety in relationships with expert and authoritative practitioners but is of limited help in understanding practitioners’ caring. Different theories that formulate practitioners’ care as altruistic, rewarded by personal connection or as a contract indicate the potential importance of practitioners’ emotions, values and sense of role in understanding their clinical communication. Conclusion Extending the theoretical grounding of clinical communication can accommodate patients’ dependence and practitioners’ caring without return to medical paternalism. Practice implications A broader theoretical base will help educators to address the inherent subjectivity of clinical relationships, and researchers to distinguish scientific questions about how patients and clinicians are from normative questions about how they should be. PMID:19157761

Clinical implications of basic science discoveries: janus resurrected--two faces of B cell and plasma cell biology.

PubMed

Woodle, E S; Rothstein, D M

2015-01-01

B cells play a complex role in the immune response. In addition to giving rise to plasma cells (PCs) and promoting T cell responses via antigen presentation, they perform immunoregulatory functions. This knowledge has created concerns regarding nonspecific B cell depletional therapy because of the potential to paradoxically augment immune responses. Recent studies now indicate that PCs have immune functions beyond immunoglobulin synthesis. Evidence for a new role for PCs as potent regulatory cells (via IL-10 and IL-35 production) is discussed including the implications for PC-targeted therapies currently being developed for clinical transplantation. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Erectile dysfunction and coronary atherothrombosis in diabetic patients: pathophysiology, clinical features and treatment.

PubMed

Gazzaruso, Carmine

2006-03-01

The current review reports recent data available in the literature on the prevalence of erectile dysfunction and the association of erectile dysfunction with overt and silent coronary artery disease in patients with diabetes mellitus. The mechanisms by which erectile dysfunction is associated with coronary artery disease and potential clinical implications of this association have been extensively analysed. In particular, the role of endothelial dysfunction in the pathophysiology of erectile dysfunction and the potential clinical usefulness of erectile dysfunction to identify diabetic patients with silent coronary artery disease have been outlined. Finally, recent guidelines on the treatment of erectile dysfunction with phosphodiesterase-5 inhibitors in diabetic patients with and without coronary artery disease have been reported and discussed.

Modeling the Financial and Clinical Implications of Malaria Rapid Diagnostic Tests in the Case-management of Older Children and Adults in Kenya

PubMed Central

Zurovac, Dejan; Larson, Bruce A.; Skarbinski, Jacek; Slutsker, Laurence; Snow, Robert W.; Hamel, Mary J.

2008-01-01

Using data on clinical practices for outpatients 5 years and older, test accuracy, and malaria prevalence, we model financial and clinical implications of malaria rapid diagnostic tests (RDTs) under the new artemether-lumefantrine (AL) treatment policy in one high and one low malaria prevalence district in Kenya. In the high transmission district, RDTs as actually used would improve malaria treatment (61% less over-treatment but 8% more under-treatment) and lower costs (21% less). Nonetheless, the majority of patients with malaria would not be correctly treated with AL. In the low transmission district, especially because the treatment policy was new and AL was not widely used, RDTs as actually used would yield a minor reduction in under-treatment errors (36% less but the base is small) with 41% higher costs. In both districts, adherence to revised clinical practices with RDTs has the potential to further decrease treatment errors with acceptable costs. PMID:18541764

The biology, function and clinical implications of exosomes in lung cancer.

PubMed

Zhou, Li; Lv, Tangfeng; Zhang, Qun; Zhu, Qingqing; Zhan, Ping; Zhu, Suhua; Zhang, Jianya; Song, Yong

2017-10-28

Exosomes are 30-100 nm small membrane vesicles of endocytic origin that are secreted by all types of cells, and can also be found in various body fluids. Increasing evidence implicates that exosomes confer stability and can deliver their cargos such as proteins and nucleic acids to specific cell types, which subsequently serve as important messengers and carriers in lung carcinogenesis. Here, we describe the biogenesis and components of exosomes mainly in lung cancer, we summarize their function in lung carcinogenesis (epithelial mesenchymal transition, oncogenic cell transformation, angiogenesis, metastasis and immune response in tumor microenvironment), and importantly we focus on the clinical potential of exosomes as biomarkers and therapeutics in lung cancer. In addition, we also discuss current challenges that might impede the clinical use of exosomes. Further studies on the functional roles of exosomes in lung cancer requires thorough research. Copyright © 2017 Elsevier B.V. All rights reserved.

Work Satisfaction and Performance of Physicians in Pediatric Outpatient Clinics

PubMed Central

Nathanson, Constance A.; Becker, Marshall H.

1973-01-01

The sources and consequences of variations in work satisfaction are investigated in a study of approximately 100 physicians in six pediatric outpatient clinics, half of them associated with teaching hospitals and half with community hospitals. Measures of work satisfaction, role conflict, and performance are related to physicians' perceived internal and external reward values, controlling for clinic attributes and physicians' background characteristics, and differences between the two clinic types are documented. Implications of the study results for potential conflict between outpatient care and academic aims in teaching hospitals are discussed and avenues of possible further research are suggested. PMID:4705214

General medicine and surgery for dental practitioners. Part 5--Psychiatry.

PubMed

Brown, S; Greenwood, M; Meechan, J G

2010-07-10

There are a significant number of patients in society who have some form of psychiatric disorder. It is important that dental practitioners have an awareness of the more common psychiatric disorders and their potential implications as they are likely to encounter them in clinical practice.

A Review of the Role of Female Gender in Autism Spectrum Disorders

ERIC Educational Resources Information Center

Kirkovski, Melissa; Enticott, Peter G.; Fitzgerald, Paul B.

2013-01-01

This paper reviews the literature exploring gender differences associated with the clinical presentation of autism spectrum disorders (ASD). The potentially mediating effect of comorbid psychopathology, biological and neurodevelopmental implications on these gender differences is also discussed. A vastly heterogeneous condition, while females on…

Mimics and chameleons in motor neurone disease

PubMed Central

Turner, Martin R; Talbot, Kevin

2013-01-01

The progression of motor neurone disease (MND) is currently irreversible, and the grave implications of diagnosis naturally fuels concern among neurologists over missing a potential mimic disorder. There is no diagnostic test for MND but in reality there are few plausible mimics in routine clinical practice. In the presence of a progressive pure motor disorder, signs such as florid fasciculations, bilateral tongue wasting, the ‘split hand’, head drop, emotionality, and cognitive or behavioural impairment carry high positive predictive value. MND is clinically heterogeneous, however, with some important chameleon-like presentations and considerable variation in clinical course. Lack of confidence about the scope of such variation, or an approach to diagnosis emphasising investigations over clinical common sense, has the potential to exacerbate diagnostic delay in MND and impede timely planning of the care which is essential to maximising quality of life. PMID:23616620

Clinical and Practical Implications of Storage Media used for Tooth Avulsion.

PubMed

Is Khinda, Vineet; Kaur, Gurpreet; S Brar, Gurlal; Kallar, Shiminder; Khurana, Heena

2017-01-01

Replantation is being widely accepted as an effective treatment option for an avulsed tooth. However, the long-term fate of replanted teeth is unpredictable; it is dependent on various factors, such as the time interval between avulsion and replantation, extra-alveolar storage period (dry storage or storage media), the vitality status of pulp or periodontal tissues and the type and period of splinting. The appropriate use of storage media is an important clinical factor affecting the postoperative prognosis of avulsed teeth following replantation. Hank's balanced salt solution and pasteurized milk are considered to be the most appropriate and clinically recommended storage media for avulsed teeth. The present review discusses the various available storage media for avulsed teeth and their potential maintenance of the vitality of periodontal ligament cells. A brief overview of the effect of clinical factors, such as the storage time, pH, and the osmolar-ity of storage media on their efficacy is included. Khinda VIS, Kaur G, Brar GS, Kallar S, Khurana H. Clinical and Practical Implications of Storage Media used for Tooth Avulsion. Int J Clin Pediatr Dent 2017; 10(2): 158-165.

Bundled payments in orthopedic surgery.

PubMed

Bushnell, Brandon D

2015-02-01

As a result of reading this article, physicians should be able to: 1. Describe the concept of bundled payments and the potential applications of bundled payments in orthopedic surgery. 2. For specific situations, outline a clinical episode of care, determine the participants in a bundling situation, and define care protocols and pathways. 3. Recognize the importance of resource utilization management, quality outcome measurement, and combined economic-clinical value in determining the value of bundled payment arrangements. 4. Identify the implications of bundled payments for practicing orthopedists, as well as the legal issues and potential future directions of this increasingly popular alternative payment method. Bundled payments, the idea of paying a single price for a bundle of goods and services, is a financial concept familiar to most American consumers because examples appear in many industries. The idea of bundled payments has recently gained significant momentum as a financial model with the potential to decrease the significant current costs of health care. Orthopedic surgery as a field of medicine is uniquely positioned for success in an environment of bundled payments. This article reviews the history, logistics, and implications of the bundled payment model relative to orthopedic surgery. Copyright 2015, SLACK Incorporated.

Long Non-Coding RNA as Potential Biomarker for Prostate Cancer: Is It Making a Difference?

PubMed

Deng, Junli; Tang, Jie; Wang, Guo; Zhu, Yuan-Shan

2017-03-07

Whole genome transcriptomic analyses have identified numerous long non-coding RNA (lncRNA) transcripts that are increasingly implicated in cancer biology. LncRNAs are found to promote essential cancer cell functions such as proliferation, invasion, and metastasis, with the potential to serve as novel biomarkers of various cancers and to further reveal uncharacterized aspects of tumor biology. However, the biological and molecular mechanisms as well as the clinical applications of lncRNAs in diverse diseases are not completely understood, and remain to be fully explored. LncRNAs may be critical players and regulators in prostate cancer carcinogenesis and progression, and could serve as potential biomarkers for prostate cancer. This review focuses on lncRNA biomarkers that are already available for clinical use and provides an overview of lncRNA biomarkers that are under investigation for clinical development in prostate cancer.

Quality of clinical supervision and counselor emotional exhaustion: the potential mediating roles of organizational and occupational commitment.

PubMed

Knudsen, Hannah K; Roman, Paul M; Abraham, Amanda J

2013-01-01

Counselor emotional exhaustion has negative implications for treatment organizations as well as the health of counselors. Quality clinical supervision is protective against emotional exhaustion, but research on the mediating mechanisms between supervision and exhaustion is limited. Drawing upon data from 934 counselors affiliated with treatment programs in the National Institute on Drug Abuse's Clinical Trials Network (CTN), this study examined commitment to the treatment organization and commitment to the counseling occupation as potential mediators of the relationship between quality clinical supervision and emotional exhaustion. The final ordinary least squares (OLS) regression model, which accounted for the nesting of counselors within treatment organizations, indicated that these two types of commitment were plausible mediators of the association between clinical supervision and exhaustion. Higher quality clinical supervision was strongly correlated with commitment to the treatment organization as well as commitment to the occupation of SUD counseling. These findings suggest that quality clinical supervision has the potential to yield important benefits for counselor well-being by strengthening ties to both their employing organization as well the larger treatment field, but longitudinal research is needed to establish these causal relationships. Copyright © 2013 Elsevier Inc. All rights reserved.

Quality of clinical supervision and counselor emotional exhaustion: The potential mediating roles of organizational and occupational commitment

PubMed Central

Knudsen, Hannah K.; Roman, Paul M.; Abraham, Amanda J.

2013-01-01

Counselor emotional exhaustion has negative implications for treatment organizations as well as the health of counselors. Quality clinical supervision is protective against emotional exhaustion, but research on the mediating mechanisms between supervision and exhaustion is limited. Drawing upon data from 934 counselors affiliated with treatment programs in the National Institute on Drug Abuse’s Clinical Trials Network (CTN), this study examined commitment to the treatment organization and commitment to the counseling occupation as potential mediators of the relationship between quality clinical supervision and emotional exhaustion. The final ordinary least squares (OLS) regression model, which accounted for the nesting of counselors within treatment organizations, indicated that these two types of commitment were plausible mediators of the association between clinical supervision and exhaustion. Higher quality clinical supervision was strongly correlated with commitment to the treatment organization as well as commitment to the occupation of SUD counseling. These findings suggest that quality clinical supervision has the potential to yield important benefits for counselor well-being by strengthening ties to both their employing organization as well the larger treatment field, but longitudinal research is needed to establish these causal relationships. PMID:23312873

Comparison of gestational dating methods and implications for exposure-outcome associations: an example with PM2.5 and preterm birth

EPA Science Inventory

OBJECTIVES: Estimating gestational age is usually based on date of last menstrual period (LMP) or clinical estimation (CE); both approaches introduce potential bias. Differences in methods of estimation may lead to misclassificat ion and inconsistencies in risk estimates, particu...

Mood instability: significance, definition and measurement.

PubMed

Broome, M R; Saunders, K E A; Harrison, P J; Marwaha, S

2015-10-01

Mood instability is common, and an important feature of several psychiatric disorders. We discuss the definition and measurement of mood instability, and review its prevalence, characteristics, neurobiological correlates and clinical implications. We suggest that mood instability has underappreciated transdiagnostic potential as an investigational and therapeutic target. © The Royal College of Psychiatrists 2015.

Harms, benefits, and the nature of interventions in pragmatic clinical trials.

PubMed

Ali, Joseph; Andrews, Joseph E; Somkin, Carol P; Rabinovich, C Egla

2015-10-01

To produce evidence capable of informing healthcare decision making at all critical levels, pragmatic clinical trials are diverse both in terms of the type of intervention (medical, behavioral, and/or technological) and the target of intervention (patients, clinicians, and/or healthcare system processes). Patients and clinicians may be called on to participate as designers, investigators, intermediaries, or subjects of pragmatic clinical trials. Other members of the healthcare team, as well as the healthcare system itself, also may be affected directly or indirectly before, during, or after study implementation. This diversity in the types and targets of pragmatic clinical trial interventions has brought into focus the need to consider whether existing ethics and regulatory principles, policies, and procedures are appropriate for pragmatic clinical trials. Specifically, further examination is needed to identify how the types and targets of pragmatic clinical trial interventions may influence the assessment of net potential risk, understood as the balance of potential harms and benefits. In this article, we build on scholarship seeking to align ethics and regulatory requirements with potential research risks and propose an approach to the assessment of net risks that is sensitive to the diverse nature of pragmatic clinical trial interventions. We clarify the potential harms, burdens, benefits, and advantages of common types of pragmatic clinical trial interventions and discuss implications for patients, clinicians, and healthcare systems. © The Author(s) 2015.

What if pediatric residents could bill for their outpatient services?

PubMed

Ng, M; Lawless, S T

2001-10-01

We prospectively studied the potential of billing and coding practices of pediatric residents in outpatient clinics and extrapolated our results to assess the financial implications of billing inaccuracies. Using Medicare as a common measure of "currency," we also used the relative value unit (RVU) and ambulatory payment class methodologies as means of assessing the productivity and financial value of resident-staffed pediatric clinics. Residents were asked to submit voluntarily shadow billing forms and documentation of outpatient clinic visits. Documentation of work was assessed by a blinded reviewer, and current procedure terminology evaluation and management codes were assigned. Comparisons between resident codes and calculated codes were made. Financial implications of physician productivity were calculated in terms of dollar amounts and RVUs. Resource intensity was measured using the ambulatory payment class methodology. A total of 344 charts were reviewed. Coding agreement for health maintenance visits was 86%, whereas agreement for acute care visits was 38%. Eighty-three percent of coding disagreement in the latter group was resulting from undercoding by residents. Errors accounted for a 4.79% difference in potential reimbursement for all visit types and a 19.10% difference for acute care visits. No significant differences in shadow billing discrepancies were found between different levels of training. Residents were predicted to generate $67 230, $87 593, and $96 072 in Medicare revenue in the outpatient clinic setting during each successive year of training. On average, residents generated 1.17 +/- 0.01 and 0.81 +/- 0.02 work RVUs for each health maintenance visit and office visit, respectively. Annual productivity from outpatient clinic settings was estimated at 548, 735, and 893 work RVUs in the postgraduate levels 1, 2, and 3, respectively. When pediatric residents are not trained adequately in proper coding practices, the potential for billing discrepancies is high and potential reimbursement differences may be substantial. Discussion of financial issues should be considered in curriculum development.

Integrated tumor and germline whole-exome sequencing identifies mutations in MAPK and PI3K pathway genes in an adolescent with rosette-forming glioneuronal tumor of the fourth ventricle

PubMed Central

Lin, Frank Y.; Bergstrom, Katie; Person, Richard; Bavle, Abhishek; Ballester, Leomar Y.; Scollon, Sarah; Raesz-Martinez, Robin; Jea, Andrew; Birchansky, Sherri; Wheeler, David A.; Berg, Stacey L.; Chintagumpala, Murali M.; Adesina, Adekunle M.; Eng, Christine; Roy, Angshumoy; Plon, Sharon E.; Parsons, D. Williams

2016-01-01

The integration of genome-scale studies such as whole-exome sequencing (WES) into the clinical care of children with cancer has the potential to provide insight into the genetic basis of an individual's cancer with implications for clinical management. This report describes the results of clinical tumor and germline WES for a patient with a rare tumor diagnosis, rosette-forming glioneuronal tumor of the fourth ventricle (RGNT). Three pathogenic gene alterations with implications for clinical care were identified: somatic activating hotspot mutations in FGFR1 (p.N546K) and PIK3CA (p.H1047R) and a germline pathogenic variant in PTPN11 (p.N308S) diagnostic for Noonan syndrome. The molecular landscape of RGNT is not well-described, but these data are consistent with prior observations regarding the importance of the interconnected MAPK and PI3K/AKT/mTOR signaling pathways in this rare tumor. The co-occurrence of FGFR1, PIK3CA, and PTPN11 alterations provides further evidence for consideration of RGNT as a distinct molecular entity from pediatric low-grade gliomas and suggests potential therapeutic strategies for this patient in the event of tumor recurrence as novel agents targeting these pathways enter pediatric clinical trials. Although RGNT has not been definitively linked with cancer predisposition syndromes, two prior cases have been reported in patients with RASopathies (Noonan syndrome and neurofibromatosis type 1 [NF1]), providing an additional link between these tumors and the mitogen-activated protein kinase (MAPK) signaling pathway. In summary, this case provides an example of the potential for genome-scale sequencing technologies to provide insight into the biology of rare tumors and yield both tumor and germline results of potential relevance to patient care. PMID:27626068

Ethical implications of digital communication for the patient-clinician relationship: analysis of interviews with clinicians and young adults with long term conditions (the LYNC study).

PubMed

Ignatowicz, Agnieszka; Slowther, Anne-Marie; Elder, Patrick; Bryce, Carol; Hamilton, Kathryn; Huxley, Caroline; Forjaz, Vera; Sturt, Jackie; Griffiths, Frances

2018-02-23

Digital communication between a patient and their clinician offers the potential for improved patient care, particularly for young people with long term conditions who are at risk of service disengagement. However, its use raises a number of ethical questions which have not been explored in empirical studies. The objective of this study was to examine, from the patient and clinician perspective, the ethical implications of the use of digital clinical communication in the context of young people living with long-term conditions. A total of 129 semi-structured interviews, 59 with young people and 70 with healthcare professionals, from 20 United Kingdom (UK)-based specialist clinics were conducted as part of the LYNC study. Transcripts from five sites (cancer, liver, renal, cystic fibrosis and mental health) were read by a core team to identify explicit and implicit ethical issues and develop descriptive ethical codes. Our subsequent thematic analysis was developed iteratively with reference to professional and ethical norms. Clinician participants saw digital clinical communication as potentially increasing patient empowerment and autonomy; improving trust between patient and healthcare professional; and reducing harm because of rapid access to clinical advice. However, they also described ethical challenges, including: difficulty with defining and maintaining boundaries of confidentiality; uncertainty regarding the level of consent required; and blurring of the limits of a clinician's duty of care when unlimited access is possible. Paradoxically, the use of digital clinical communication can create dependence rather than promote autonomy in some patients. Patient participants varied in their understanding of, and concern about, confidentiality in the context of digital communication. An overarching theme emerging from the data was a shifting of the boundaries of the patient-clinician relationship and the professional duty of care in the context of use of clinical digital communication. The ethical implications of clinical digital communication are complex and go beyond concerns about confidentiality and consent. Any development of this form of communication should consider its impact on the patient-clinician-relationship, and include appropriate safeguards to ensure that professional ethical obligations are adhered to.

Non-hemodynamic effects of organic nitrates and the distinctive characteristics of pentaerithrityl tetranitrate.

PubMed

Gori, Tommaso; Daiber, Andreas

2009-01-01

Organic nitrates are among the oldest and yet most commonly employed drugs in the long-term therapy of coronary artery disease and congestive heart failure. While they have long been used in clinical practice, our understanding of their mechanism of action and side effects remains incomplete. For instance, recent findings provide evidence of previously unanticipated, non-hemodynamic properties that include potentially beneficial mechanisms (such as the induction of a protective phenotype that mimics ischemic preconditioning), but also toxic effects (such as endothelial and autonomic dysfunction, rebound angina, tolerance). To date, the most commonly employed organic nitrates are isosorbide mononitrate, isosorbide dinitrate, and nitroglycerin (glyceryl trinitrate). Another organic nitrate, pentaerithrityl tetranitrate (PETN), has long been employed in eastern European countries and is currently being reintroduced in Western countries. In light of their wide use, and of the (re)introduction of PETN in Western markets, the present review focuses on the novel effects of organic nitrates, describing their potential clinical implications and discussing differences among different compounds. We believe that these recent findings have important clinical implications. Since the side effects of organic nitrates such as nitroglycerin and isosorbides appear to be mediated by reactive oxygen species, care should be taken that drugs with antioxidant properties are co-administered. On the other hand, efforts should be made to clinically exploit the preconditioning effects of these drugs.

Perspective: New Recommendations for the Treatment of Systemic Hypertension and their Potential Implications for Glaucoma Management.

PubMed

De Moraes, Carlos Gustavo; Cioffi, George A; Weinreb, Robert N; Liebmann, Jeffrey M

2018-05-10

There is compelling evidence that low systemic blood pressure is associated with glaucoma prevalence and progression. Recently, new guidelines for treatment of systemic hypertension have been implemented and recommend lower target blood pressure. These guidelines may have implications on the rates of glaucoma progression seen in clinical practice and how clinicians should be prepared to identify patients at risk. More importantly, a new paradigm to monitor glaucoma progression is patients treated for systemic hypertension may be warranted in light of these recent changes.

Time course of clinical change following neurofeedback.

PubMed

Rance, Mariela; Walsh, Christopher; Sukhodolsky, Denis G; Pittman, Brian; Qiu, Maolin; Kichuk, Stephen A; Wasylink, Suzanne; Koller, William N; Bloch, Michael; Gruner, Patricia; Scheinost, Dustin; Pittenger, Christopher; Hampson, Michelle

2018-05-02

Neurofeedback - learning to modulate brain function through real-time monitoring of current brain state - is both a powerful method to perturb and probe brain function and an exciting potential clinical tool. For neurofeedback effects to be useful clinically, they must persist. Here we examine the time course of symptom change following neurofeedback in two clinical populations, combining data from two ongoing neurofeedback studies. This analysis reveals a shared pattern of symptom change, in which symptoms continue to improve for weeks after neurofeedback. This time course has several implications for future neurofeedback studies. Most neurofeedback studies are not designed to test an intervention with this temporal pattern of response. We recommend that new studies incorporate regular follow-up of subjects for weeks or months after the intervention to ensure that the time point of greatest effect is sampled. Furthermore, this time course of continuing clinical change has implications for crossover designs, which may attribute long-term, ongoing effects of real neurofeedback to the control intervention that follows. Finally, interleaving neurofeedback sessions with assessments and examining when clinical improvement peaks may not be an appropriate approach to determine the optimal number of sessions for an application. Copyright © 2018 Elsevier Inc. All rights reserved.

Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing.

PubMed

Mandelker, Diana; Zhang, Liying; Kemel, Yelena; Stadler, Zsofia K; Joseph, Vijai; Zehir, Ahmet; Pradhan, Nisha; Arnold, Angela; Walsh, Michael F; Li, Yirong; Balakrishnan, Anoop R; Syed, Aijazuddin; Prasad, Meera; Nafa, Khedoudja; Carlo, Maria I; Cadoo, Karen A; Sheehan, Meg; Fleischut, Megan H; Salo-Mullen, Erin; Trottier, Magan; Lipkin, Steven M; Lincoln, Anne; Mukherjee, Semanti; Ravichandran, Vignesh; Cambria, Roy; Galle, Jesse; Abida, Wassim; Arcila, Marcia E; Benayed, Ryma; Shah, Ronak; Yu, Kenneth; Bajorin, Dean F; Coleman, Jonathan A; Leach, Steven D; Lowery, Maeve A; Garcia-Aguilar, Julio; Kantoff, Philip W; Sawyers, Charles L; Dickler, Maura N; Saltz, Leonard; Motzer, Robert J; O'Reilly, Eileen M; Scher, Howard I; Baselga, Jose; Klimstra, David S; Solit, David B; Hyman, David M; Berger, Michael F; Ladanyi, Marc; Robson, Mark E; Offit, Kenneth

2017-09-05

Guidelines for cancer genetic testing based on family history may miss clinically actionable genetic changes with established implications for cancer screening or prevention. To determine the proportion and potential clinical implications of inherited variants detected using simultaneous sequencing of the tumor and normal tissue ("tumor-normal sequencing") compared with genetic test results based on current guidelines. From January 2014 until May 2016 at Memorial Sloan Kettering Cancer Center, 10 336 patients consented to tumor DNA sequencing. Since May 2015, 1040 of these patients with advanced cancer were referred by their oncologists for germline analysis of 76 cancer predisposition genes. Patients with clinically actionable inherited mutations whose genetic test results would not have been predicted by published decision rules were identified. Follow-up for potential clinical implications of mutation detection was through May 2017. Tumor and germline sequencing compared with the predicted yield of targeted germline sequencing based on clinical guidelines. Proportion of clinically actionable germline mutations detected by universal tumor-normal sequencing that would not have been detected by guideline-directed testing. Of 1040 patients, the median age was 58 years (interquartile range, 50.5-66 years), 65.3% were male, and 81.3% had stage IV disease at the time of genomic analysis, with prostate, renal, pancreatic, breast, and colon cancer as the most common diagnoses. Of the 1040 patients, 182 (17.5%; 95% CI, 15.3%-19.9%) had clinically actionable mutations conferring cancer susceptibility, including 149 with moderate- to high-penetrance mutations; 101 patients tested (9.7%; 95% CI, 8.1%-11.7%) would not have had these mutations detected using clinical guidelines, including 65 with moderate- to high-penetrance mutations. Frequency of inherited mutations was related to case mix, stage, and founder mutations. Germline findings led to discussion or initiation of change to targeted therapy in 38 patients tested (3.7%) and predictive testing in the families of 13 individuals (1.3%), including 6 for whom genetic evaluation would not have been initiated by guideline-based testing. In this referral population with selected advanced cancers, universal sequencing of a broad panel of cancer-related genes in paired germline and tumor DNA samples was associated with increased detection of individuals with potentially clinically significant heritable mutations over the predicted yield of targeted germline testing based on current clinical guidelines. Knowledge of these additional mutations can help guide therapeutic and preventive interventions, but whether all of these interventions would improve outcomes for patients with cancer or their family members requires further study. clinicaltrials.gov Identifier: NCT01775072.

Induced pluripotent stem cells--alchemist's tale or clinical reality?

PubMed

Rashid, S Tamir; Vallier, Ludovic

2010-08-13

Following Shinya Yamanaka's first report describing the reprogramming of fibroblasts into stem cells over three years ago, some sceptics initially drew analogies between this new field of research and the quasi-mystical practice of 'alchemy'. Unlike the alchemist, however, stem cell researchers have rigorously tested and repeated experiments, proving their very own brand of cellular 'alchemy' to be a reality, with potentially massive implications for the study of human biology and clinical medicine. These investigations have resulted in an explosion of related publications and initiated the field of stem cell research known as 'induced pluripotency'. In this review, we give an account of the historical development, current technologies and potential clinical applications of induced pluripotency and conclude with a perspective on the possible future directions for this dynamic field.

To B or not to B cells-mediate a healthy start to life.

PubMed

Nguyen, T G; Ward, C M; Morris, J M

2013-02-01

Maternal immune responses during pregnancy are critical in programming the future health of a newborn. The maternal immune system is required to accommodate fetal immune tolerance as well as to provide a protective defence against infections for the immunocompromised mother and her baby during gestation and lactation. Natural immunity and antibody production by maternal B cells play a significant role in providing such immunoprotection. However, aberrations in the B cell compartment as a consequence of maternal autoimmunity can pose serious risks to both the mother and her baby. Despite their potential implication in shaping pregnancy outcomes, the role of B cells in human pregnancy has been poorly studied. This review focuses on the role of B cells and the implications of B cell depletion therapy in pregnancy. It highlights the evidence of an association between aberrant B cell compartment and obstetric conditions. It also alludes to the potential mechanisms that amplify these B cell aberrances and thereby contribute to exacerbation of some maternal autoimmune conditions and poor neonatal outcomes. Clinical and experimental evidence suggests strongly that maternal autoantibodies contribute directly to the pathologies of obstetric and neonatal conditions that have significant implications for the lifelong health of a newborn. The evidence for clinical benefit and safety of B cell depletion therapies in pregnancy is reviewed, and an argument is mounted for further clinical evaluation of B cell-targeted therapies in high-risk pregnancy, with an emphasis on improving neonatal outcomes and prevention of neonatal conditions such as congenital heart block and fetal/neonatal alloimmune thrombocytopenia. © 2012 British Society for Immunology.

Impact of Genetics on the Clinical Management of Channelopathies

PubMed Central

Schwartz, Peter J.; Ackerman, Michael J.; George, Alfred L.; Wilde, Arthur A.M.

2013-01-01

There are few areas in cardiology where the impact of genetics and of genetic testing on clinical management has been as great as in cardiac channelopathies, arrhythmic disorders of genetic origin related to the ionic control of the cardiac action potential. Among the growing number of diseases identified as channelopathies, three are sufficiently prevalent to represent significant clinical and societal problems and to warrant adequate understanding by practicing cardiologists: long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and Brugada syndrome. This review will focus selectively on the impact of genetic discoveries on clinical management of these three diseases. For each disorder, we will discuss to what extent genetic knowledge and clinical genetic test results modify the way cardiologists should approach and manage affected patients. We will also address the optimal use of genetic testing including its potential limitations and the potential medico-legal implications when such testing is not performed. We will highlight how important can be to understand the ways by which genotype can impact clinical manifestations, risk stratification, and responses to the therapy. We will also illustrate the close bridge between molecular biology and clinical medicine, and will emphasize that consideration of the genetic basis for these hereditable arrhythmia syndromes, as well as the proper use and interpretation of clinical genetic testing, should remain the standard-of-care. PMID:23684683

Thymoquinone, as an anticancer molecule: from basic research to clinical investigation

PubMed Central

Asaduzzaman Khan, Md.; Tania, Mousumi; Fu, Shangyi; Fu, Junjiang

2017-01-01

Thymoquinone is an anticancer phytochemical commonly found in black cumin. In this review, we discuss the potential of thymoquinone as anticancer molecule, its mechanism of action and future usage in clinical applications. Thymoquinone exhibits anticancer activity via numerous mechanisms of action, specifically by showing selective antioxidant and oxidant activity, interfering with DNA structure, affecting carcinogenic signaling molecules/pathways and immunomodulation. In vitro activity of thymoquinone has been further implicated in animal models of cancer; however, no clinical application has been proven yet. This is the optimum time to focus on clinical trials for developing thymoquinone as a future drug in cancer therapeutics. PMID:28881699

Thymoquinone, as an anticancer molecule: from basic research to clinical investigation.

PubMed

Asaduzzaman Khan, Md; Tania, Mousumi; Fu, Shangyi; Fu, Junjiang

2017-08-01

Thymoquinone is an anticancer phytochemical commonly found in black cumin. In this review, we discuss the potential of thymoquinone as anticancer molecule, its mechanism of action and future usage in clinical applications. Thymoquinone exhibits anticancer activity via numerous mechanisms of action, specifically by showing selective antioxidant and oxidant activity, interfering with DNA structure, affecting carcinogenic signaling molecules/pathways and immunomodulation. In vitro activity of thymoquinone has been further implicated in animal models of cancer; however, no clinical application has been proven yet. This is the optimum time to focus on clinical trials for developing thymoquinone as a future drug in cancer therapeutics.

Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies

NASA Astrophysics Data System (ADS)

Giardiello, Marco; Liptrott, Neill J.; McDonald, Tom O.; Moss, Darren; Siccardi, Marco; Martin, Phil; Smith, Darren; Gurjar, Rohan; Rannard, Steve P.; Owen, Andrew

2016-10-01

Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes.

Overcoming Barriers to Increase the Contribution of Clinical Psychologists to Work With Persons With Severe Mental Illness.

PubMed

Roe, David; Yanos, Philip T; Lysaker, Paul H

2006-12-01

Psychosocial treatments for persons with severe mental illness (SMI) have been developing rapidly over the past decade. Despite the fact that people with SMI are often in the greatest need of care, clinical psychologists are not currently playing a major role in their treatment and are underrepresented compared to other disciplines in this area such as nursing, social work, and psychiatry. In this article, we present possible reasons for clinical psychologists' underrepresentation and discuss motivators, potential opportunities, and ways for clinical psychologists to take a greater role in the provision of services for persons with SMI. Implications for the training of clinical psychologists are discussed.

Genetic testing in the epilepsies—Report of the ILAE Genetics Commission

PubMed Central

Ottman, Ruth; Hirose, Shinichi; Jain, Satish; Lerche, Holger; Lopes-Cendes, Iscia; Noebels, Jeffrey L.; Serratosa, José; Zara, Federico; Scheffer, Ingrid E.

2010-01-01

SUMMARY In this report, the International League Against Epilepsy (ILAE) Genetics Commission discusses essential issues to be considered with regard to clinical genetic testing in the epilepsies. Genetic research on the epilepsies has led to the identification of more than 20 genes with a major effect on susceptibility to idiopathic epilepsies. The most important potential clinical application of these discoveries is genetic testing: the use of genetic information, either to clarify the diagnosis in people already known or suspected to have epilepsy (diagnostic testing), or to predict onset of epilepsy in people at risk because of a family history (predictive testing). Although genetic testing has many potential benefits, it also has potential harms, and assessment of these potential benefits and harms in particular situations is complex. Moreover, many treating clinicians are unfamiliar with the types of tests available, how to access them, how to decide whether they should be offered, and what measures should be used to maximize benefit and minimize harm to their patients. Because the field is moving rapidly, with new information emerging practically every day, we present a framework for considering the clinical utility of genetic testing that can be applied to many different syndromes and clinical contexts. Given the current state of knowledge, genetic testing has high0020clinical utility in few clinical contexts, but in some of these it carries implications for daily clinical practice. PMID:20100225

An FDA Perspective on the Regulatory Implications of Complex Signatures to Predict Response to Targeted Therapies

PubMed Central

Beaver, Julia A.; Tzou, Abraham; Blumenthal, Gideon M.; McKee, Amy E.; Kim, Geoffrey; Pazdur, Richard; Philip, Reena

2016-01-01

As technologies evolve, and diagnostics move from detection of single biomarkers toward complex signatures, an increase in the clinical use and regulatory submission of complex signatures is anticipated. However, to date, no complex signatures have been approved as companion diagnostics. In this article, we will describe the potential benefit of complex signatures and their unique regulatory challenges including analytical performance validation, complex signature simulation, and clinical performance evaluation. We also will review the potential regulatory pathways for clearance, approval, or acceptance of complex signatures by the U.S. Food and Drug Administration (FDA). These regulatory pathways include regulations applicable to in vitro diagnostic devices, including companion diagnostic devices, the potential for labeling as a complementary diagnostic, and the biomarker qualification program. PMID:27993967

Adult cyclical vomiting syndrome: a disorder of allostatic regulation?

PubMed

Levinthal, D J; Bielefeldt, K

2014-08-01

Cyclic vomiting syndrome (CVS) is an idiopathic illness characterized by stereotypic and sudden-onset episodes of intense retching and repetitive vomiting that are often accompanied by severe abdominal pain. Many associated factors that predict CVS attacks, such as prolonged periods of fasting, sleep deprivation, physical and emotional stress, or acute anxiety, implicate sympathetic nervous system activation as a mechanism that may contribute to CVS pathogenesis. Furthermore, adult patients with CVS tend to have a history of early adverse life events, mood disorders, chronic stress, and drug abuse-all associations that may potentiate sympathetic neural activity. In this review, we set forth a conceptual model in which CVS is viewed as a brain disorder involving maladaptive plasticity within central neural circuits important for allostatic regulation of the sympathetic nervous system. This model not only can account for the varied clinical observations that are linked with CVS, but also has implications for potential therapeutic interventions. Thus, it is likely that cognitive behavioral therapy, stress management ("mind-body") interventions, regular exercise, improved sleep, and avoidance of cannabis and opiate use could have positive influences on the clinical course for patients with CVS.

An Overview of Achalasia and Its Subtypes

PubMed Central

Patel, Dhyanesh A.; Lappas, Brian M.

2017-01-01

Achalasia is one of the most studied esophageal motility disorders. However, the pathophysiology and reasons that patients develop achalasia are still unclear. Patients often present with dysphagia to solids and liquids, regurgitation, and varying degrees of weight loss. There is significant latency prior to diagnosis, which can have nutritional implications. The diagnosis is suspected based on clinical history and confirmed by esophageal high-resolution manometry testing. Esophagogastroduodenoscopy is necessary to rule out potential malignancy that can mimic achalasia. Recent data presented in abstract form suggest that patients with type II achalasia may be most likely, and patients with type III achalasia may be least likely, to report weight loss compared to patients with type I achalasia. Although achalasia cannot be permanently cured, palliation of symptoms is possible in over 90% of patients with the treatment modalities currently available (pneumatic dilation, Heller myotomy, or peroral endoscopic myotomy). This article reviews the clinical presentation, diagnosis, and management options in patients with achalasia, as well as potential insights into histopathologic differences and nutritional implications of the subtypes of achalasia. PMID:28867969

Understanding the aetiology and resolution of chronic otitis media from animal and human studies

PubMed Central

Thornton, Ruth B.; Kirkham, Lea-Ann S.; Kerschner, Joseph E.; Cheeseman, Michael T.

2017-01-01

ABSTRACT Inflammation of the middle ear, known clinically as chronic otitis media, presents in different forms, such as chronic otitis media with effusion (COME; glue ear) and chronic suppurative otitis media (CSOM). These are highly prevalent diseases, especially in childhood, and lead to significant morbidity worldwide. However, much remains unclear about this disease, including its aetiology, initiation and perpetuation, and the relative roles of mucosal and leukocyte biology, pathogens, and Eustachian tube function. Chronic otitis media is commonly modelled in mice but most existing models only partially mimic human disease and many are syndromic. Nevertheless, these models have provided insights into potential disease mechanisms, and have implicated altered immune signalling, mucociliary function and Eustachian tube function as potential predisposing mechanisms. Clinical studies of chronic otitis media have yet to implicate a particular molecular pathway or mechanism, and current human genetic studies are underpowered. We also do not fully understand how existing interventions, such as tympanic membrane repair, work, nor how chronic otitis media spontaneously resolves. This Clinical Puzzle article describes our current knowledge of chronic otitis media and the existing research models for this condition. It also identifies unanswered questions about its pathogenesis and treatment, with the goal of advancing our understanding of this disease to aid the development of novel therapeutic interventions. PMID:29125825

Clinical implications of risk aversion: an online study of risk-avoidance and treatment utilization in pathological anxiety.

PubMed

Lorian, Carolyn N; Grisham, Jessica R

2011-08-01

Previous research suggests that the pervasive tendency to avoid perceived risks (i.e., the safety bias) may be implicated in the maintenance of pathological anxiety. These studies have not explored, however, the potential clinical implications of such a bias, such as the influence of risk aversion on treatment seeking. The aim of this study was to investigate how risk-avoidance is related to willingness to seek treatment in an online sample of clinically anxious individuals with social phobia (SP), obsessive-compulsive disorder (OCD) and generalized anxiety disorder (GAD). Healthy control participants (n=117) and those endorsing criteria for one or more anxiety disorder(s) (n=92; SP, n=33; OCD, n=19; GAD, n=40) were recruited from various online sources. Respondents completed an online survey comprised of a validated diagnostic interview, self-report measures assessing for symptom severity, risk-taking across various domains, a generalized index of risk-taking and treatment utilization. Consistent with hypotheses, SP and GAD individuals reported significantly more risk-avoidance when compared to non-clinical controls. Furthermore, willingness to seek treatment was found to be positively associated with social risk-taking and generalized risk-taking orientation in clinically anxious individuals who had never sought treatment. These results suggest that certain individual cognitive factors may contribute to the decision to seek treatment and may provide an interesting avenue of future investigation for increasing service utilization and treatment seeking in anxious populations. Copyright © 2011 Elsevier Ltd. All rights reserved.

In silico cancer modeling: is it ready for primetime?

PubMed Central

Deisboeck, Thomas S; Zhang, Le; Yoon, Jeongah; Costa, Jose

2011-01-01

SUMMARY At the dawn of the era of personalized, systems-driven medicine, computational or in silico modeling and the simulation of disease processes is becoming increasingly important for hypothesis generation and data integration in both experiment and clinics alike. Arguably, this is nowhere more visible than in oncology. To illustrate the field’s vast potential as well as its current limitations we briefly review selected works on modeling malignant brain tumors. Implications for clinical practice, including trial design and outcome prediction are also discussed. PMID:18852721

Genetic testing in hyperlipidemia.

PubMed

Bilen, Ozlem; Pokharel, Yashashwi; Ballantyne, Christie M

2015-05-01

Hereditary dyslipidemias are often underdiagnosed and undertreated, yet with significant health implications, most importantly causing preventable premature cardiovascular diseases. The commonly used clinical criteria to diagnose hereditary lipid disorders are specific but are not very sensitive. Genetic testing may be of value in making accurate diagnosis and improving cascade screening of family members, and potentially, in risk assessment and choice of therapy. This review focuses on using genetic testing in the clinical setting for lipid disorders, particularly familial hypercholesterolemia. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetic Testing in Hyperlipidemia.

PubMed

Bilen, Ozlem; Pokharel, Yashashwi; Ballantyne, Christie M

2016-03-01

Hereditary dyslipidemias are often underdiagnosed and undertreated, yet with significant health implications, most importantly causing preventable premature cardiovascular diseases. The commonly used clinical criteria to diagnose hereditary lipid disorders are specific but are not very sensitive. Genetic testing may be of value in making accurate diagnosis and improving cascade screening of family members, and potentially, in risk assessment and choice of therapy. This review focuses on using genetic testing in the clinical setting for lipid disorders, particularly familial hypercholesterolemia. Copyright © 2016 Elsevier Inc. All rights reserved.

Financial conflict-of-interest policies in clinical research: issues for clinical investigators.

PubMed

Boyd, Elizabeth A; Cho, Mildred K; Bero, Lisa A

2003-08-01

As industry sponsorship of clinical research grows, investigators' personal financial relationships with those sponsors are under increasing scrutiny. The federal government, some states, and many universities have enacted conflict-of-interest policies to monitor and regulate investigators' financial relationships. Little is known, however, about investigators' awareness of or support for these policies or their attitudes toward regulatory efforts. To explore the possible implications of conflict-of-interest policies for clinical researchers, the authors interviewed active clinical investigators at two institutions where the conflict-of-interest policies differ. The most striking feature of the interviews was the range of perceptions and attitudes expressed by clinical investigators and their implications for administrators, professional societies, and policymakers concerned with conflicts of interest. Fewer than half of the interviewed investigators could accurately describe their campus' conflict-of-interest policy. Many investigators felt that professional societies, the public, and individual investigators were appropriate monitors of conflicts of interest. Many investigators recognized the general risks associated with conflicts of interest, but felt that they personally were not at risk. A fundamental challenge facing administrators and policymakers is to demonstrate to all investigators, both clinical and nonclinical, that the potential for bias, pressure and conflict is relevant to all investigators with industry relationships.

Pediatric misophonia with comorbid obsessive-compulsive spectrum disorders.

PubMed

Webber, Troy A; Johnson, Patricia L; Storch, Eric A

2014-01-01

Misophonia is a potentially debilitating condition characterized by increased sensitivity to specific sounds, which cause subsequent behavioral and emotional responses. The nature, clinical phenomenology and etiology of misophonia remain unclear, and misophonic clinical presentations are not currently accounted for by existing psychiatric or audiological disorders. We present a case of pediatric misophonia in the context of comorbid obsessive-compulsive disorder and Tourette's syndrome. Given the interrelationships among obsessive-compulsive spectrum disorders and misophonia, these disorders may share underlying pathophysiology, particularly within the dopaminergic and serotonergic neural systems. Clinical (i.e., treatment) and theoretical implications are discussed. Published by Elsevier Inc.

Liquid Biopsy in Head and Neck Cancer: Promises and Challenges.

PubMed

Nonaka, T; Wong, D T W

2018-06-01

Head and neck cancer is the sixth most common cancer worldwide. It remains one of the leading causes of death, and its early detection is crucial. Liquid biopsy has emerged as a promising tool for detecting and monitoring the disease status of patients with early and advanced cancers. Circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomal miRNAs have received enormous attention because of their apparent clinical implications. Analyses of these circulating biomarkers have paved the way for novel therapeutic approaches and precision medicine. A growing number of reports have implicated the use of circulating biomarkers for detection, treatment planning, response monitoring, and prognosis assessment. Although these new biomarkers can provide a wide range of possible clinical applications, no validated circulating biomarkers have yet been integrated into clinical practice for head and neck cancer. In this review, we summarize the current knowledge of circulating biomarkers in this field, focusing on their feasibility, limitations, and key areas of clinical applications. We also highlight recent advances in salivary diagnostics and their potential application in head and neck cancer.

Body habitus in heart failure: understanding the mechanisms and clinical significance of the obesity paradox.

PubMed

Parto, Parham; Lavie, Carl J; Arena, Ross; Bond, Samantha; Popovic, Dejana; Ventura, Hector O

2016-11-01

The prevalence of obesity among adults and children worldwide has reached epic proportions and has become a major independent risk factor for the development of heart failure (HF), in addition to a contributor of hypertension and cardiovascular disease. The implications of obesity in the development of HF involve adverse effects on cardiac structure and function. Despite all of this, in the setting of chronic HF, excess body mass is associated with improved clinical outcomes, demonstrating the presence of an obesity paradox. In this review, we will discuss the gender differences, global application, potential mechanisms and role of interventions based on fitness and purposeful weight loss as potential therapeutic strategies.

Pathobiology of Anaplastic Large Cell Lymphoma

PubMed Central

Piccaluga, Pier Paolo; Gazzola, Anna; Mannu, Claudia; Agostinelli, Claudio; Bacci, Francesco; Sabattini, Elena; Sagramoso, Carlo; Piva, Roberto; Roncolato, Fernando; Inghirami, Giorgio; Pileri, Stefano A.

2010-01-01

The authors revise the concept of anaplastic large cell lymphoma (ALCL) in the light of the recently updated WHO classification of Tumors of Hematopoietic and Lymphoid Tissues both on biological and clinical grounds. The main histological findings are illustrated with special reference to the cytological spectrum that is indeed characteristic of the tumor. The phenotype is reported in detail: the expression of the ALK protein as well as the chromosomal abnormalities is discussed with their potential pathogenetic implications. The clinical features of ALCL are presented by underlining the difference in terms of response to therapy and survival between the ALK-positive and ALK-negative forms. Finally, the biological rationale for potential innovative targeted therapies is presented. PMID:21331150

The entry-level occupational therapy clinical doctorate: The next education wave of change in Canada?

PubMed

Brown, Ted; Crabtree, Jeffrey L; Wells, Joe; Mu, Keli

2016-12-01

Currently, Canada and the United States are the only two countries that mandate entry to the occupational therapy profession at the master's level. There was a recommendation considered by the American Occupational Therapy Association that by 2025 all education programs would move to the clinical doctorate level. In August 2015, the Accreditation Council for Occupational Therapy Education made the formal decision that for now, the entry-level qualification for occupational therapists in the United States will remain at both the master's and clinical doctorate levels. This article presents an overview of the types of doctorates available, the pros and cons of moving to the clinical doctorate, and some potential questions that will need to be considered. Is the next step in the educational progression of occupational therapy in Canada the entry-level clinical doctorate? What are the potential implications for the profession, our clients, and funders? Further discourse and investigation of this issue is needed.

The pediatric sepsis biomarker risk model: potential implications for sepsis therapy and biology.

PubMed

Alder, Matthew N; Lindsell, Christopher J; Wong, Hector R

2014-07-01

Sepsis remains a major cause of morbidity and mortality in adult and pediatric intensive care units. Heterogeneity of demographics, comorbidities, biological mechanisms, and severity of illness leads to difficulty in determining which patients are at highest risk of mortality. Determining mortality risk is important for weighing the potential benefits of more aggressive interventions and for deciding whom to enroll in clinical trials. Biomarkers can be used to parse patients into different risk categories and can outperform current methods of patient risk stratification based on physiologic parameters. Here we review the Pediatric Sepsis Biomarker Risk Model that has also been modified and applied to estimate mortality risk in adult patients. We compare the two models and speculate on the biological implications of the biomarkers in patients with sepsis.

α-Synuclein oligomers and clinical implications for Parkinson disease

PubMed Central

Kalia, Lorraine V.; Kalia, Suneil K.; McLean, Pamela J.; Lozano, Andres M.; Lang, Anthony E.

2012-01-01

Protein aggregation within the central nervous system has been recognized as a defining feature of neurodegenerative diseases since the early 20th century. Since that time, there has been a growing list of neurodegenerative disorders, including Parkinson disease, which are characterized by inclusions of specific pathogenic proteins. This has led to the long-held dogma that these characteristic protein inclusions, which are composed of large insoluble fibrillar protein aggregates and visible by light microscopy, are responsible for cell death in these diseases. However, the correlation between protein inclusion formation and cytotoxicity is inconsistent suggesting another form of the pathogenic proteins may be contributing to neurodegeneration. There is emerging evidence implicating soluble oligomers, smaller protein aggregates not detectable by conventional microscopy, as potential culprits in the pathogenesis of neurodegenerative diseases. The protein α-synuclein is well recognized to contribute to the pathogenesis of Parkinson disease and is the major component of Lewy bodies and Lewy neurites. However, α-synuclein also forms oligomeric species with certain conformations being toxic to cells. The mechanisms by which these α-synuclein oligomers cause cell death are being actively investigated as they may provide new strategies for diagnosis and treatment of Parkinson disease and related disorders. Here we review the possible role of α-synuclein oligomers in cell death in Parkinson disease and discuss the potential clinical implications. PMID:23225525

The Vicious Cycle of Myostatin Signaling in Sarcopenic Obesity: Myostatin Role in Skeletal Muscle Growth, Insulin Signaling and Implications for Clinical Trials.

PubMed

Consitt, L A; Clark, B C

2018-01-01

The age-related loss of skeletal muscle (sarcopenia) is a major health concern as it is associated with physical disability, metabolic impairments, and increased mortality. The coexistence of sarcopenia with obesity, termed 'sarcopenic obesity', contributes to skeletal muscle insulin resistance and the development of type 2 diabetes, a disease prevalent with advancing age. Despite this knowledge, the mechanisms contributing to sarcopenic obesity remain poorly understood, preventing the development of targeted therapeutics. This article will discuss the clinical and physiological consequences of sarcopenic obesity and propose myostatin as a potential candidate contributing to this condition. A special emphasis will be placed on examining the role of myostatin signaling in impairing both skeletal muscle growth and insulin signaling. In addition, the role of myostatin in regulating muscle-to fat cross talk, further exacerbating metabolic dysfunction in the elderly, will be highlighted. Lastly, we discuss how this knowledge has implications for the design of myostatin-inhibitor clinical trials.

Clinical Implications From an Exploratory Study of Postural Management of Breech Presentation

PubMed Central

Founds, Sandra A.

2013-01-01

The results from an exploratory study of the effectiveness of maternal knee-chest posture for producing cephalic version of breech presentation are shown. Methods are briefly described and clinical implications are presented. Among 25 women, fewer who performed the maternal knee-chest postural intervention experienced fetal cephalic version than women in the control group who did nothing to influence breech presentation. Despite limitations of the underpowered findings, trends in the data may indicate that parity and gestational age were potentially relevant covariates of version. Postural management is not an evidence-based practice. This exploratory study indicates that maternal knee-chest posture may work opposite to the expected direction, but the small sample size precludes generalizations about efficacy of knee-chest postural management. At least one adequately powered trial that controls for parity and gestational age is needed to determine whether knee-chest postural management results in no effect, a small, or small to moderate clinically significant effect. PMID:16814225

Analytical Methods for Quantification of Vitamin D and Implications for Research and Clinical Practice.

PubMed

Stokes, Caroline S; Lammert, Frank; Volmer, Dietrich A

2018-02-01

A plethora of contradictory research surrounds vitamin D and its influence on health and disease. This may, in part, result from analytical difficulties with regard to measuring vitamin D metabolites in serum. Indeed, variation exists between analytical techniques and assays used for the determination of serum 25-hydroxyvitamin D. Research studies into the effects of vitamin D on clinical endpoints rely heavily on the accurate assessment of vitamin D status. This has important implications, as findings from vitamin D-related studies to date may potentially have been hampered by the quantification techniques used. Likewise, healthcare professionals are increasingly incorporating vitamin D testing and supplementation regimens into their practice, and measurement errors may be also confounding the clinical decisions. Importantly, the Vitamin D Standardisation Programme is an initiative that aims to standardise the measurement of vitamin D metabolites. Such a programme is anticipated to eliminate the inaccuracies surrounding vitamin D quantification. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Immunologic advances in monoclonal antibody therapy: implications for oncology nursing.

PubMed

Karius, D; Marriott, M A

1997-04-01

To provide an overview of monoclonal antibody (MoAb) formation, therapeutic and diagnostic uses of MoAbs, and the implications for oncology nurses. Books and Journal articles (including research studies). Clinical trials have demonstrated the diagnostic and therapeutic potential of MoAb therapy. Advances in hybridoma technology and gene-splicing techniques have led to the formation of chimeric MoAbs, which exhibit decreased immunogenicity in the recipient. Clinical limitations with MoAb therapy include cross-reactivity with normal tissues, heterogeneity of antigen expression, presence of circulating antigen, antigenic modulation, tumor size and vascularity, and the anti-antibody response. MoAbs currently are used for diagnostic purposes and in phase I, II, and III clinical trials for cancer treatment. As research progresses, MoAbs are likely to be incorporated into the mainstream of cancer therapy as have other biologic response modifiers. Current uses of MoAb therapy in clinical trials involve nurses in many roles, including clinical nurse specialist, staff nurse, and research nurse. As more oncology nurses encounter MoAb therapy in practice, they will have to have an increased understanding of basic immunologic principles and the expertise to manage the unique toxicities associated with MoAb therapy.

Orienting hypnosis.

PubMed

Hope, Anna E; Sugarman, Laurence I

2015-01-01

This article presents a new frame for understanding hypnosis and its clinical applications. Despite great potential to transform health and care, hypnosis research and clinical integration is impaired in part by centuries of misrepresentation and ignorance about its demonstrated efficacy. The authors contend that advances in the field are primarily encumbered by the lack of distinct boundaries and definitions. Here, hypnosis, trance, and mind are all redefined and grounded in biological, neurological, and psychological phenomena. Solutions are proposed for boundary and language problems associated with hypnosis. The biological role of novelty stimulating an orienting response that, in turn, potentiates systemic plasticity forms the basis for trance. Hypnosis is merely the skill set that perpetuates and influences trance. This formulation meshes with many aspects of Milton Erickson's legacy and Ernest Rossi's recent theory of mind and health. Implications of this hypothesis for clinical skills, professional training, and research are discussed.

Vitamin D and Heart Failure.

PubMed

Marshall Brinkley, D; Ali, Omair M; Zalawadiya, Sandip K; Wang, Thomas J

2017-10-01

Vitamin D is principally known for its role in calcium homeostasis, but preclinical studies implicate multiple pathways through which vitamin D may affect cardiovascular function and influence risk for heart failure. Many adults with cardiovascular disease have low vitamin D status, making it a potential therapeutic target. We review the rationale and potential role of vitamin D supplementation in the prevention and treatment of chronic heart failure. Substantial observational evidence has associated low vitamin D status with the risk of heart failure, ventricular remodeling, and clinical outcomes in heart failure, including mortality. However, trials assessing the influence of vitamin D supplementation on surrogate markers and clinical outcomes in heart failure have generally been small and inconclusive. There are insufficient data to recommend routine assessment or supplementation of vitamin D for the prevention or treatment of chronic heart failure. Prospective trials powered for clinical outcomes are warranted.

Transfer of knowledge and skills: some implications for nursing and nurse education.

PubMed

Lauder, W; Reynolds, W; Angus, N

1999-08-01

The construct of transfer has enormous importance to nursing as it begins to highlight potential problems in the transfer of knowledge and skills from the campus to the clinical area, from one part of the clinical area to another (e.g. surgical to medical), and from community to the clinical area. Thus, any adequate conceptualization of transfer must account for problems of practice-practice transfer as well as theory-practice transfer. These potential problems are the concern of educators, students and managers who have a responsibility for agency nurses and bank nurses who may find themselves in different specialities on a regular basis. Transfer has relevance to a whole raft of other issues ranging from the application of theories to nursing practice, through to the validity of claims that courses which develop intellectual skills prepare nurses for lifelong learning.

Energy Drinks: Implications for the Breastfeeding Mother.

PubMed

Thorlton, Janet; Ahmed, Azza; Colby, David A

2016-01-01

Breastfeeding women may experience disrupted sleep schedules and be tempted to turn to popular energy drinks to reduce fatigue and enhance alertness, prompting the question: What are the maternal and child health implications for breastfeeding mothers consuming energy drinks? Caffeine and vitamin-rich energy drinks contain a variety of herbal ingredients and vitamins; however, ingredient amounts may not be clearly disclosed on product labels. Interactions between herbal ingredients and caffeine are understudied and not well defined in the literature. Some infants can be sensitive to caffeine and display increased irritability and sleep disturbances when exposed to caffeine from breastmilk. Breastfeeding women who consume energy drinks may be ingesting herbal ingredients that have not undergone scientific evaluation, and if taking prenatal vitamins, may unknowingly exceed the recommended daily intake. Caffeinated products are marketed in newer ways, fueling concerns about health consequences of caffeine exposure. We present implications associated with consumption of caffeine and vitamin-rich energy drinks among breastfeeding women. Product safety, labeling, common ingredients, potential interactions, and clinical implications are discussed. Healthcare providers should encourage breastfeeding women to read product labels for ingredients, carbohydrate content, serving size, and to discourage consumption of energy drinks when breastfeeding and/or taking prenatal vitamins, to avoid potential vitamin toxicity.

TRPV3 in Drug Development

PubMed Central

Broad, Lisa M.; Mogg, Adrian J.; Eberle, Elizabeth; Tolley, Marcia; Li, Dominic L.; Knopp, Kelly L.

2016-01-01

Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP (Transient Receptor Potential) super-family. It is a relatively underexplored member of the thermo-TRP sub-family (Figure 1), however, genetic mutations and use of gene knock-outs and selective pharmacological tools are helping to provide insights into its role and therapeutic potential. TRPV3 is highly expressed in skin, where it is implicated in skin physiology and pathophysiology, thermo-sensing and nociception. Gain of function TRPV3 mutations in rodent and man have enabled the role of TRPV3 in skin health and disease to be particularly well defined. Pre-clinical studies provide some rationale to support development of TRPV3 antagonists for therapeutic application for the treatment of inflammatory skin conditions, itch and pain. However, to date, only one compound directed towards block of the TRPV3 receptor (GRC15300) has progressed into clinical trials. Currently, there are no known clinical trials in progress employing a TRPV3 antagonist. PMID:27618069

Imaging the Perivascular Space as a Potential Biomarker of Neurovascular and Neurodegenerative Diseases.

PubMed

Ramirez, Joel; Berezuk, Courtney; McNeely, Alicia A; Gao, Fuqiang; McLaurin, JoAnne; Black, Sandra E

2016-03-01

Although the brain lacks conventional lymphatic vessels found in peripheral tissue, evidence suggests that the space surrounding the vasculature serves a similar role in the clearance of fluid and metabolic waste from the brain. With aging, neurodegeneration, and cerebrovascular disease, these microscopic perivascular spaces can become enlarged, allowing for visualization and quantification on structural MRI. The purpose of this review is to: (i) describe some of the recent pre-clinical findings from basic science that shed light on the potential neurophysiological mechanisms driving glymphatic and perivascular waste clearance, (ii) review some of the pathobiological etiologies that may lead to MRI-visible enlarged perivascular spaces (ePVS), (iii) describe the possible clinical implications of ePVS, (iv) evaluate existing qualitative and quantitative techniques used for measuring ePVS burden, and (v) propose future avenues of research that may improve our understanding of this potential clinical neuroimaging biomarker for fluid and metabolic waste clearance dysfunction in neurodegenerative and neurovascular diseases.

Ethical, legal and social implications of incorporating personalized medicine into healthcare.

PubMed

Brothers, Kyle B; Rothstein, Mark A

As research focused on personalized medicine has developed over the past decade, bioethics scholars have contemplated the ethical, legal and social implications of this type of research. In the next decade, there will be a need to broaden the focus of this work as personalized medicine moves into clinical settings. We consider two broad issues that will grow in importance and urgency. First, we analyze the consequences of the significant increase in health information that will be brought about by personalized medicine. Second, we raise concerns about the potential of personalized medicine to exacerbate existing disparities in healthcare.

Ethical, legal and social implications of incorporating personalized medicine into healthcare

PubMed Central

Brothers, Kyle B; Rothstein, Mark A

2015-01-01

As research focused on personalized medicine has developed over the past decade, bioethics scholars have contemplated the ethical, legal and social implications of this type of research. In the next decade, there will be a need to broaden the focus of this work as personalized medicine moves into clinical settings. We consider two broad issues that will grow in importance and urgency. First, we analyze the consequences of the significant increase in health information that will be brought about by personalized medicine. Second, we raise concerns about the potential of personalized medicine to exacerbate existing disparities in healthcare. PMID:25601880

Embolic Strokes of Unknown Source and Cryptogenic Stroke: Implications in Clinical Practice

PubMed Central

Nouh, Amre; Hussain, Mohammed; Mehta, Tapan; Yaghi, Shadi

2016-01-01

Up to a third of strokes are rendered cryptogenic or of undetermined etiology. This number is specifically higher in younger patients. At times, inadequate diagnostic workups, multiple causes, or an under-recognized etiology contributes to this statistic. Embolic stroke of undetermined source, a new clinical entity particularly refers to patients with embolic stroke for whom the etiology of embolism remains unidentified despite through investigations ruling out established cardiac and vascular sources. In this article, we review current classification and discuss important clinical considerations in these patients; highlighting cardiac arrhythmias and structural abnormalities, patent foramen ovale, paradoxical sources, and potentially under-recognized, vascular, inflammatory, autoimmune, and hematologic sources in relation to clinical practice. PMID:27047443

Abortion work: strains, coping strategies, policy implications.

PubMed

Joffe, C

1979-11-01

As a result of the moral and social conflicts surrounding abortion, workers involved in counseling potential abortion recipients are subject to certain strains. The author uses observations made at one abortion clinic to support her conclusion that these strains, as well as the methods of coping developed by staff and administration, must be considered in formulating any policy on abortion.

Testing the Long-Term Efficacy of a Prevention Program for Improving Marital Conflict in Community Families

ERIC Educational Resources Information Center

Faircloth, W. Brad; Schermerhorn, Alice C.; Mitchell, Patricia M.; Cummings, Jennifer S.; Cummings, E. Mark

2011-01-01

Family-focused prevention programs for community samples have potentially broad, clinically relevant implications but few studies have examined whether any program benefits continue to be observed over the long term. Although benefits of a marital conflict focused parent education program, the Happy Couples and Happy Kids (i.e., HCHK) program,…

Neurobiological Processes of Risk and Resilience in Adolescence: Implications for Policy and Prevention Science

ERIC Educational Resources Information Center

Busso, Daniel S.

2014-01-01

This article focuses on the concepts of risk and resilience and their potential to inform clinical interventions, school-based prevention programs, and social policies. Research suggests that childhood adversity can trigger a cascade of psychological and neurobiological events that can lead to mental disorders in later life. Yet little is known…

Work expectations, cultural sensitivity, schizophrenia, and suicide risk in male patients.

PubMed

Lewine, Richard; Shriner, Brooke

2009-04-01

This study examines the relationship between "vocational lost potential" and suicide risk in a mixed sample of severely and persistently mentally ill psychiatric patients. We hypothesized that increased lost potential would be associated with increased suicide risk indicator ratings and that this relationship would be moderated by patients' social class of origin. One hundred sixty-seven psychiatric patients rated a range of clinical symptoms and vocational expectations, as well as providing sociodemographic information including their parents' years of education (used as a proxy for social class of origin). Contrary to our prediction, the results suggest that individuals from higher social class who experience minimal lost potential may be at a higher risk for suicide than their counterparts with maximal lost potential; this is especially true when based on fathers' educational level. In discussing the clinical implications of our findings, we suggest that a subgroup of individuals' vocational success may depend on first addressing the cognitive conflict inherent in the phenomenon of lost potential.

Electronic health record tools' support of nurses' clinical judgment and team communication.

PubMed

Kossman, Susan P; Bonney, Leigh Ann; Kim, Myoung Jin

2013-11-01

Nurses need to quickly process information to form clinical judgments, communicate with the healthcare team, and guide optimal patient care. Electronic health records not only offer potential for enhanced care but also introduce unintended consequences through changes in workflow, clinical judgment, and communication. We investigated nurses' use of improvised (self-made) and electronic health record-generated cognitive artifacts on clinical judgment and team communication. Tanner's Clinical Judgment Model provided a framework and basis for questions in an online survey and focus group interviews. Findings indicated that (1) nurses rated self-made work lists and medication administration records highest for both clinical judgment and communication, (2) tools aided different dimensions of clinical judgment, and (3) interdisciplinary tools enhance team communication. Implications are that electronic health record tool redesign could better support nursing work.

[Interdisciplinary clinical pathway for colorectal cancer].

PubMed

Fischbach, W; Engemann, R

2006-07-01

Limited financial resources in public health care have led to the introduction of clinical pathways as a means to a better effectivity and efficacy. Colorectal cancer met the requirements for establishing such a pathway in a distinguished way: high patient volume, high costs, interdisciplinary multi-modal treatment concepts in a relevant frequency, and existing evidence based guidelines. This article gives an example of a clinical pathway for colorectal cancer as established in our hospital. The potential of such pathways to save costs as well as their implications on treatment results and patients' satisfaction will have to be critically analyzed in the future before their value can be definitely estimated.

Financial toxicity in cancer care.

PubMed

O'Connor, Jeremy M; Kircher, Sheetal M; de Souza, Jonas A

2016-03-01

The cost of cancer care is increasing, with important implications for the delivery of high-quality, patent-centered care. In the clinical setting, patents and physicians express a desire to discuss out-of-pocket costs. Nevertheless, both groups feel inadequately prepared to participate in these discussions, and perhaps not surprisingly, the integration of these discussions into clinical practice seems to be the exception rather than the rule. The resulting neglect of financial issues has the potential to cause unnecessary suffering for oncology patents. In this paper, we review the most relevant literature on financial toxicity in cancer care. In addition, we discuss potential predictors of financial toxicity, and the recent development of instruments to help clinicians and researchers quantify financial burden. ©2016 Frontline Medical Communications.

Physician-assisted suicide and/or euthanasia: Pragmatic implications for palliative care [corrected].

PubMed

Hudson, Peter; Hudson, Rosalie; Philip, Jennifer; Boughey, Mark; Kelly, Brian; Hertogh, Cees

2015-10-01

Despite the availability of palliative care in many countries, legalization of euthanasia and physician-assisted suicide (EAS) continues to be debated-particularly around ethical and legal issues--and the surrounding controversy shows no signs of abating. Responding to EAS requests is considered one of the most difficult healthcare responsibilities. In the present paper, we highlight some of the less frequently discussed practical implications for palliative care provision if EAS were to be legalized. Our aim was not to take an explicit anti-EAS stance or expand on findings from systematic reviews or philosophical and ethico-legal treatises, but rather to offer clinical perspectives and the potential pragmatic implications of legalized EAS for palliative care provision, patients and families, healthcare professionals, and the broader community. We provide insights from our multidisciplinary clinical experience, coupled with those from various jurisdictions where EAS is, or has been, legalized. We believe that these issues, many of which are encountered at the bedside, must be considered in detail so that the pragmatic implications of EAS can be comprehensively considered. Increased resources and effort must be directed toward training, research, community engagement, and ensuring adequate resourcing for palliative care before further consideration is given to allocating resources for legalizing euthanasia and physician-assisted suicide.

Exome and deep sequencing of clinically aggressive neuroblastoma reveal somatic mutations that affect key pathways involved in cancer progression

PubMed Central

Lasorsa, Vito Alessandro; Formicola, Daniela; Pignataro, Piero; Cimmino, Flora; Calabrese, Francesco Maria; Mora, Jaume; Esposito, Maria Rosaria; Pantile, Marcella; Zanon, Carlo; De Mariano, Marilena; Longo, Luca; Hogarty, Michael D.; de Torres, Carmen; Tonini, Gian Paolo; Iolascon, Achille; Capasso, Mario

2016-01-01

The spectrum of somatic mutation of the most aggressive forms of neuroblastoma is not completely determined. We sought to identify potential cancer drivers in clinically aggressive neuroblastoma. Whole exome sequencing was conducted on 17 germline and tumor DNA samples from high-risk patients with adverse events within 36 months from diagnosis (HR-Event3) to identify somatic mutations and deep targeted sequencing of 134 genes selected from the initial screening in additional 48 germline and tumor pairs (62.5% HR-Event3 and high-risk patients), 17 HR-Event3 tumors and 17 human-derived neuroblastoma cell lines. We revealed 22 significantly mutated genes, many of which implicated in cancer progression. Fifteen genes (68.2%) were highly expressed in neuroblastoma supporting their involvement in the disease. CHD9, a cancer driver gene, was the most significantly altered (4.0% of cases) after ALK. Other genes (PTK2, NAV3, NAV1, FZD1 and ATRX), expressed in neuroblastoma and involved in cell invasion and migration were mutated at frequency ranged from 4% to 2%. Focal adhesion and regulation of actin cytoskeleton pathways, were frequently disrupted (14.1% of cases) thus suggesting potential novel therapeutic strategies to prevent disease progression. Notably BARD1, CHEK2 and AXIN2 were enriched in rare, potentially pathogenic, germline variants. In summary, whole exome and deep targeted sequencing identified novel cancer genes of clinically aggressive neuroblastoma. Our analyses show pathway-level implications of infrequently mutated genes in leading neuroblastoma progression. PMID:27009842

Exome and deep sequencing of clinically aggressive neuroblastoma reveal somatic mutations that affect key pathways involved in cancer progression.

PubMed

Lasorsa, Vito Alessandro; Formicola, Daniela; Pignataro, Piero; Cimmino, Flora; Calabrese, Francesco Maria; Mora, Jaume; Esposito, Maria Rosaria; Pantile, Marcella; Zanon, Carlo; De Mariano, Marilena; Longo, Luca; Hogarty, Michael D; de Torres, Carmen; Tonini, Gian Paolo; Iolascon, Achille; Capasso, Mario

2016-04-19

The spectrum of somatic mutation of the most aggressive forms of neuroblastoma is not completely determined. We sought to identify potential cancer drivers in clinically aggressive neuroblastoma.Whole exome sequencing was conducted on 17 germline and tumor DNA samples from high-risk patients with adverse events within 36 months from diagnosis (HR-Event3) to identify somatic mutations and deep targeted sequencing of 134 genes selected from the initial screening in additional 48 germline and tumor pairs (62.5% HR-Event3 and high-risk patients), 17 HR-Event3 tumors and 17 human-derived neuroblastoma cell lines.We revealed 22 significantly mutated genes, many of which implicated in cancer progression. Fifteen genes (68.2%) were highly expressed in neuroblastoma supporting their involvement in the disease. CHD9, a cancer driver gene, was the most significantly altered (4.0% of cases) after ALK.Other genes (PTK2, NAV3, NAV1, FZD1 and ATRX), expressed in neuroblastoma and involved in cell invasion and migration were mutated at frequency ranged from 4% to 2%.Focal adhesion and regulation of actin cytoskeleton pathways, were frequently disrupted (14.1% of cases) thus suggesting potential novel therapeutic strategies to prevent disease progression.Notably BARD1, CHEK2 and AXIN2 were enriched in rare, potentially pathogenic, germline variants.In summary, whole exome and deep targeted sequencing identified novel cancer genes of clinically aggressive neuroblastoma. Our analyses show pathway-level implications of infrequently mutated genes in leading neuroblastoma progression.

Women physicians as healthcare leaders: a qualitative study.

PubMed

Roth, Virginia R; Theriault, Anne; Clement, Chris; Worthington, Jim

2016-06-20

Purpose - The purpose of this paper is to explore the under-representation of women physicians in clinical leadership by examining the issue from their perspective. Design/methodology/approach - The authors used large group engagement methods to explore the experiences and perceptions of women physicians. In order to capture common themes across this group as a whole, participants were selected using purposeful sampling. Data were analysed using a structured thematic analysis procedure. Findings - This paper provides empirical insights into the influences affecting women physicians' decision to participate in leadership. The authors found that they often exclude themselves because the costs of leadership outweigh the benefits. Potential barriers unique to healthcare include the undervaluing of leadership by physician peers and perceived lack of support by nursing. Research limitations/implications - This study provides an in-depth examination of why women physicians are under-represented in clinical leadership from the perspective of those directly involved. Further studies are needed to confirm the generalizability of these findings and potential differences between demographic groups of physicians. Practical implications - Healthcare organizations seeking to increase the participation of women physicians in leadership should focus on modifying the perceived costs of leadership and highlighting the potential benefits. Large group engagement methods can be an effective approach to engage physicians on specific issues and mobilize grass-roots support for change. Originality/value - This exploratory study provides insights on the barriers and enablers to leadership specific to women physicians in the clinical setting. It provides a reference for healthcare organizations seeking to develop and diversify their leadership talent.

Prescription opioid abuse, pain and addiction: Clinical issues and implications

PubMed Central

LING, WALTER; MOONEY, LARISSA; HILLHOUSE, MAUREEN

2014-01-01

Issues Prescription opioid misuse in the USA has increased over threefold since 1990 to epidemic proportions, with substantial increases in prescription opioid use also reported in other countries, such as Australia and New Zealand. The broad availability of prescription pain medications, coupled with public misconceptions about their safety and addictive potential, have contributed to the recent surge in non-medical use of prescription opioids and corresponding increases in treatment admissions for problems related to opioid misuse. Given competing pressures faced by physicians to both diagnose and treat pain syndromes and identify individuals at risk for addictive disorders, the use of opioids in the treatment of pain poses a significant clinical challenge. Approach This paper reviews the interaction between pain and opioid addiction with a focus on clinical management issues, including risk factors for opioid dependence in patients with chronic pain and the use of assessment tools to identify and monitor at-risk individuals. Treatment options for opioid dependence and pain are reviewed, including the use of the partial μ agonist buprenorphine in the management of concurrent pain and opioid addiction. Implications Physicians should strive to find a reasonable balance between minimising potential adverse effects of opioid medications without diminishing legitimate access to opioids for analgesia. Conclusions The article discusses the need to identify methods for minimising risks and negative consequences associated with opioid analgesics and poses research directions, including the development of abuse-deterrent opioid formulations, genetic risk factors for opioid dependence and opioid-induced hyperalgesia as a potential target for medication therapy. PMID:21545561

Eating disorder symptoms and parenting styles.

PubMed

Haycraft, Emma; Blissett, Jackie

2010-02-01

This study aimed to examine associations between symptoms of eating disorders and parenting style, in a non-clinical sample. One hundred and five mothers completed self-report measures of eating disorder symptoms and parenting style. Higher levels of eating disorder symptoms were associated with more authoritarian and permissive parenting styles. Authoritative parenting was not significantly related to eating disorder symptoms. The findings demonstrate that eating disorder symptoms in non-clinical individuals are related to less adaptive parenting styles. These findings have potential implications for clinicians working with mothers with eating disorders. 2009 Elsevier Ltd. All rights reserved.

Significance of Medicare and Medicaid Programs for the Practice of Medicine

PubMed Central

DeWalt, Darren A.; Oberlander, Jonathan; Carey, Timothy S.; Roper, William L.

2005-01-01

The 1965 legislation that established Medicare and Medicaid declared that the Federal Government would not interfere in clinical medicine. Despite the original intent, Medicare and Medicaid have had tremendous influence on medical practice. In this article, we focus on four policy areas that illustrate the influence of CMS (and its predecessor agencies) on medical practice. We discuss the implications of the relationship between CMS and clinical medicine and how this relationship has changed over time. We conclude with thoughts about potential future efforts at CMS. PMID:17290639

Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies

PubMed Central

Giardiello, Marco; Liptrott, Neill J.; McDonald, Tom O.; Moss, Darren; Siccardi, Marco; Martin, Phil; Smith, Darren; Gurjar, Rohan; Rannard, Steve P.; Owen, Andrew

2016-01-01

Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes. PMID:27767027

Role of Obesity in Asthma: Mechanisms and Management Strategies.

PubMed

Scott, Hayley A; Wood, Lisa G; Gibson, Peter G

2017-08-01

Obesity is a commonly reported comorbidity in asthma, particularly in severe asthma. Obese asthmatics are highly symptomatic with a poor quality of life, despite using high-dose inhaled corticosteroids. While the clinical manifestations have been documented, the aetiologies of obese-asthma remain unclear. Several potential mechanisms have been proposed, including poor diet quality, physical inactivity and consequent accrual of excess adipose tissue. Each of these factors independently activates inflammatory pathways, potentially exerting effects in the airways. Because the origins of obesity are multifactorial, it is now believed there are multiple obese-asthma phenotypes, with varied aetiologies and clinical consequences. In this review, we will describe the clinical implications of obesity in people with asthma, our current understanding of the mechanisms driving this association and describe recently proposed obese-asthma phenotypes. We will then discuss how asthma management is complicated by obesity, and provide graded recommendations for the management of obesity in this population.

Clinical potentials of human pluripotent stem cells in lung diseases

PubMed Central

2014-01-01

Lung possesses very limited regenerative capacity. Failure to maintain homeostasis of lung epithelial cell populations has been implicated in the development of many life-threatening pulmonary diseases leading to substantial morbidity and mortality worldwide, and currently there is no known cure for these end-stage pulmonary diseases. Embryonic stem cells (ESCs) and somatic cell-derived induced pluripotent stem cells (iPSCs) possess unlimited self-renewal capacity and great potential to differentiate to various cell types of three embryonic germ layers (ectodermal, mesodermal, and endodermal). Therapeutic use of human ESC/iPSC-derived lung progenitor cells for regeneration of injured or diseased lungs will have an enormous clinical impact. This article provides an overview of recent advances in research on pluripotent stem cells in lung tissue regeneration and discusses technical challenges that must be overcome for their clinical applications in the future. PMID:24995122

Nail toxicity induced by cancer chemotherapy.

PubMed

Gilbar, Peter; Hain, Alice; Peereboom, Veta-Marie

2009-09-01

To provide a comprehensive literature review of chemotherapy-induced nail toxicity, including clinical presentation, implicated drugs and approaches for prevention and management. A search of MEDLINE and EMBASE (1966-2008) databases was conducted using the terms (and variations of the terms) antineoplastic agents, nails, nail toxicity, onycholysis, and paronychia. Bibliographies from selected articles were reviewed for appropriate references. The retrieved literature was reviewed to include all articles relevant to the clinical presentation, diagnosis, incidence, prevention, and treatment of chemotherapy-induced nail toxicity. Nail toxicity is a relatively uncommon adverse effect linked to a number of chemotherapeutic agents. Clinical presentation varies, depending on which nail structure is affected and the severity of the insult. Nail changes may involve all or some nails. Toxicity may be asymptomatic and limited to cosmetic concerns, however, more severe effects, involving pain and discomfort can occur. Taxanes and anthracyclines are the antineoplastic drug groups most commonly implicated. It is suggested that the administration schedule may influence the incidence of nail abnormalities, for example reported cases linked to the weekly administration of paclitaxel.Before instituting chemotherapy, patients should be educated regarding potential nail toxicities and strategies for prevention implemented. Management includes appropriate nail cutting, avoiding potential irritants, topical, or oral antimicrobials, and possibly cessation or dose reduction of the offending agent. Cryotherapy, through the application of frozen gloves or socks, has been beneficial in reducing docetaxel-induced nail toxicity and may be effective for other drugs.

The Aging Cardiovascular System: Understanding It at the Cellular and Clinical Levels.

PubMed

Paneni, Francesco; Diaz Cañestro, Candela; Libby, Peter; Lüscher, Thomas F; Camici, Giovanni G

2017-04-18

Cardiovascular disease (CVD) presents a great burden for elderly patients, their caregivers, and health systems. Structural and functional alterations of vessels accumulate throughout life, culminating in increased risk of developing CVD. The growing elderly population worldwide highlights the need to understand how aging promotes CVD in order to develop new strategies to confront this challenge. This review provides examples of some major unresolved clinical problems encountered in daily cardiovascular practice as we care for elderly patients. Next, the authors summarize the current understanding of the mechanisms implicated in cardiovascular aging, and the potential for targeting novel pathways implicated in endothelial dysfunction, mitochondrial oxidative stress, chromatin remodeling, and genomic instability. Lastly, the authors consider critical aspects of vascular repair, including autologous transplantation of bone marrow-derived stem cells in elderly patients. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Implications of genome-wide association studies in cancer therapeutics.

PubMed

Patel, Jai N; McLeod, Howard L; Innocenti, Federico

2013-09-01

Genome wide association studies (GWAS) provide an agnostic approach to identifying potential genetic variants associated with disease susceptibility, prognosis of survival and/or predictive of drug response. Although these techniques are costly and interpretation of study results is challenging, they do allow for a more unbiased interrogation of the entire genome, resulting in the discovery of novel genes and understanding of novel biological associations. This review will focus on the implications of GWAS in cancer therapy, in particular germ-line mutations, including findings from major GWAS which have identified predictive genetic loci for clinical outcome and/or toxicity. Lessons and challenges in cancer GWAS are also discussed, including the need for functional analysis and replication, as well as future perspectives for biological and clinical utility. Given the large heterogeneity in response to cancer therapeutics, novel methods of identifying mechanisms and biology of variable drug response and ultimately treatment individualization will be indispensable. © 2013 The British Pharmacological Society.

Traumatogenic Processes and Pathways to Mental Health Outcomes for Sexual Minorities Exposed to Bias Crime Information.

PubMed

Lannert, Brittany K

2015-07-01

Vicarious traumatization of nonvictim members of communities targeted by bias crimes has been suggested by previous qualitative studies and often dominates public discussion following bias events, but proximal and distal responses of community members have yet to be comprehensively modeled, and quantitative research on vicarious responses is scarce. This comprehensive review integrates theoretical and empirical literatures in social, clinical, and physiological psychology in the development of a model of affective, cognitive, and physiological responses of lesbian, gay, and bisexual individuals upon exposure to information about bias crimes. Extant qualitative research in vicarious response to bias crimes is reviewed in light of theoretical implications and methodological limitations. Potential pathways to mental health outcomes are outlined, including accumulative effects of anticipatory defensive responding, multiplicative effects of minority stress, and putative traumatogenic physiological and cognitive processes of threat. Methodological considerations, future research directions, and clinical implications are also discussed. © The Author(s) 2014.

Mental Imagery in Depression: Phenomenology, Potential Mechanisms, and Treatment Implications.

PubMed

Holmes, Emily A; Blackwell, Simon E; Burnett Heyes, Stephanie; Renner, Fritz; Raes, Filip

2016-01-01

Mental imagery is an experience like perception in the absence of a percept. It is a ubiquitous feature of human cognition, yet it has been relatively neglected in the etiology, maintenance, and treatment of depression. Imagery abnormalities in depression include an excess of intrusive negative mental imagery; impoverished positive imagery; bias for observer perspective imagery; and overgeneral memory, in which specific imagery is lacking. We consider the contribution of imagery dysfunctions to depressive psychopathology and implications for cognitive behavioral interventions. Treatment advances capitalizing on the representational format of imagery (as opposed to its content) are reviewed, including imagery rescripting, positive imagery generation, and memory specificity training. Consideration of mental imagery can contribute to clinical assessment and imagery-focused psychological therapeutic techniques and promote investigation of underlying mechanisms for treatment innovation. Research into mental imagery in depression is at an early stage. Work that bridges clinical psychology and neuroscience in the investigation of imagery-related mechanisms is recommended.

Albumin in chronic liver disease: structure, functions and therapeutic implications.

PubMed

Spinella, Rosaria; Sawhney, Rohit; Jalan, Rajiv

2016-01-01

Human serum albumin is a critical plasma protein produced by the liver with a number of accepted clinical indications in chronic liver disease including management of circulatory and renal dysfunction in patients with ascites. Advanced cirrhosis is characterised by reduced albumin concentration as well as impaired albumin function as a result of specific structural changes and oxidative damage. Traditionally, the biologic and therapeutic role of albumin in liver disease was attributed to its oncotic effects but it is now understood that albumin has a wide range of other important physiologic functions such as immunomodulation, endothelial stabilisation, antioxidant effects and binding multiple drugs, toxins and other molecules. This review discusses the multifunctional properties of albumin and, in particular, the biologic and clinical implications of structural and functional changes of albumin that are associated with cirrhosis. Based on these insights, we explore the current and potential future therapeutic uses of albumin in liver disease.

Attachment and Chronic Pain in Children and Adolescents

PubMed Central

Donnelly, Theresa J.; Jaaniste, Tiina

2016-01-01

Although attachment theory is not new, its theoretical implications for the pediatric chronic pain context have not been thoroughly considered, and the empirical implications and potential clinical applications are worth exploring. The attachment framework broadly focuses on interactions between a child’s developing self-regulatory systems and their caregiver’s responses. These interactions are believed to create a template for how individuals will relate to others in the future, and may help account for normative and pathological patterns of emotions and behavior throughout life. This review outlines relevant aspects of the attachment framework to the pediatric chronic pain context. The theoretical and empirical literature is reviewed regarding the potential role of attachment-based constructs such as vulnerability and maintaining factors of pediatric chronic pain. The nature and targets of attachment-based pediatric interventions are considered, with particular focus on relevance for the pediatric chronic pain context. The potential role of attachment style in the transition from acute to chronic pain is considered, with further research directions outlined. PMID:27792141

Implication of microRNAs in the development and potential treatment of radiation-induced heart disease.

PubMed

Kura, Branislav; Babal, Pavel; Slezak, Jan

2017-10-01

Radiotherapy is the most commonly used methodology to treat oncological disease, one of the most widespread causes of death worldwide. Oncological patients cured by radiotherapy applied to the mediastinal area have been shown to suffer from cardiovascular disease. The increase in the prevalence of radiation-induced heart disease has emphasized the need to seek new therapeutic targets to mitigate the negative impact of radiation on the heart. In this regard, microRNAs (miRNAs) have received considerable interest. miRNAs regulate post-transcriptional gene expression by their ability to target various mRNA sequences because of their imperfect pairing with mRNAs. It has been recognized that miRNAs modulate a diverse spectrum of cardiac functions with developmental, pathophysiological, and clinical implications. This makes them promising potential targets for diagnosis and treatment. This review summarizes the recent findings about the possible involvement of miRNAs in radiation-induced heart disease and their potential use as diagnostic or treatment targets in this respect.

Transient abnormal Q waves during exercise electrocardiography

PubMed Central

Alameddine, F F; Zafari, A M

2004-01-01

Myocardial ischaemia during exercise electrocardiography is usually manifested by ST segment depression or elevation. Transient abnormal Q waves are rare, as Q waves indicate an old myocardial infarction. The case of a patient with exercise induced transient abnormal Q waves is reported. The potential mechanisms involved in the development of such an abnormality and its clinical implications are discussed. PMID:14676264

Treatment and disease management of multiple sclerosis patients: A review for nurse practitioners.

PubMed

Roman, Cortnee; Menning, Kara

2017-10-01

This review discusses the role of the nurse practitioner (NP) in evaluating the clinical effects, potential side effects, and monitoring requirements for treatment options in multiple sclerosis (MS) and provides guidance on how to help patients understand these issues. A literature search was conducted on PubMed to identify publications on monitoring and disease management of MS patients. Additional resources included drug information web sites and package inserts. NPs play an active role in the management of MS patients via effective monitoring and communication throughout the patient's treatment regimen and disease course. In the shared decision-making model of MS treatment, NPs ensure that patients understand the implications of their disease-modifying therapies (DMTs). As patients move through treatments during the course of their disease, the importance of this role increases, and it is critical that NPs follow the guidelines in each medication's product label and take into account any potential lingering effects of prior medications. It is critical for NPs to promote patient adherence, to ensure that patients understand treatment side effects and monitoring requirements, and to take sequencing and reversibility implications of DMTs into account when making clinical decisions. ©2017 American Association of Nurse Practitioners.

Stem Cell Research and Clinical Translation: A Roadmap about Good Clinical Practice and Patient Care

PubMed Central

Scopetti, Matteo; Gatto, Vittorio

2017-01-01

The latest research achievements in the field of stem cells led in 2016 to the publication of “Guidelines for Stem Cell Research and Clinical Translation” by the International Society for Stem Cell Research (ISSCR). Updating the topics covered in previous publications, the new recommendations offer interesting ethical and scientific insights. Under the common principles of research integrity, protection of patient's welfare, respect for the research subjects, transparency and social justice, the centrality of good clinical practice, and informed consent in research and translational medicine is supported. The guidelines implement the abovementioned publications, requiring rigor in all areas of research, promoting the validity of the scientific activity results and emphasizing the need for an accurate and efficient public communication. This paper aims to analyze the aforementioned guidelines in order to provide a valid interpretive tool for experts. In particular, a research activity focused on the bioethical, scientific, and social implications of the new recommendations is carried out in order to provide food for thought. Finally, as an emerging issue of potential impact of current guidelines, an overview on implications of compensation for egg donation is offered. PMID:29090010

Obesity Paradox in Lung Cancer Prognosis: Evolving Biological Insights and Clinical Implications.

PubMed

Zhang, Xueli; Liu, Yamin; Shao, Hua; Zheng, Xiao

2017-10-01

The survival rate of lung cancer remains low despite the progress of surgery and chemotherapy. With the increasing comorbidity of obesity in patients with lung cancer, new challenges are emerging in the management of this patient population. A key issue of interest is the prognostic effect of obesity on surgical and chemotherapeutic outcomes in patients with lung cancer, which is fueled by the growing observation of survival benefits in overweight or obese patients. This unexpected inverse relationship between obesity and lung cancer mortality, called the obesity paradox, remains poorly understood. The evolving insights into the heterogeneity of obesity phenotypes and associated biological connections with lung cancer progression in recent years may help explain some of the seemingly paradoxical relationship, and well-designed clinical studies looking at the causal role of obesity-associated molecules are expected. Here, we examine potential biological mechanisms behind the protective effects of obesity in lung cancer. We highlight the need to clarify the clinical implications of this relationship toward an updated intervention strategy in the clinical care of patients with lung cancer and obesity. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Stem Cell Research and Clinical Translation: A Roadmap about Good Clinical Practice and Patient Care.

PubMed

Frati, Paola; Scopetti, Matteo; Santurro, Alessandro; Gatto, Vittorio; Fineschi, Vittorio

2017-01-01

The latest research achievements in the field of stem cells led in 2016 to the publication of "Guidelines for Stem Cell Research and Clinical Translation" by the International Society for Stem Cell Research (ISSCR). Updating the topics covered in previous publications, the new recommendations offer interesting ethical and scientific insights. Under the common principles of research integrity, protection of patient's welfare, respect for the research subjects, transparency and social justice, the centrality of good clinical practice, and informed consent in research and translational medicine is supported. The guidelines implement the abovementioned publications, requiring rigor in all areas of research, promoting the validity of the scientific activity results and emphasizing the need for an accurate and efficient public communication. This paper aims to analyze the aforementioned guidelines in order to provide a valid interpretive tool for experts. In particular, a research activity focused on the bioethical, scientific, and social implications of the new recommendations is carried out in order to provide food for thought. Finally, as an emerging issue of potential impact of current guidelines, an overview on implications of compensation for egg donation is offered.

Population-based analysis of patients with COPD in Catalonia: a cohort study with implications for clinical management

PubMed Central

Vela, Emili; Tényi, Ákos; Cano, Isaac; Monterde, David; Cleries, Montserrat; Garcia-Altes, Anna; Hernandez, Carme; Escarrabill, Joan; Roca, Josep

2018-01-01

Background Clinical management of patients with chronic obstructive pulmonary disease (COPD) shows potential for improvement provided that patients’ heterogeneities are better understood. The study addresses the impact of comorbidities and its role in health risk assessment. Objective To explore the potential of health registry information to enhance clinical risk assessment and stratification. Design Fixed cohort study including all registered patients with COPD in Catalonia (Spain) (7.5 million citizens) at 31 December 2014 with 1-year (2015) follow-up. Methods A total of 264 830 patients with COPD diagnosis, based on the International Classification of Diseases (Ninth Revision) coding, were assessed. Performance of multiple logistic regression models for the six main dependent variables of the study: mortality, hospitalisations (patients with one or more admissions; all cases and COPD-related), multiple hospitalisations (patients with at least two admissions; all causes and COPD-related) and users with high healthcare costs. Neither clinical nor forced spirometry data were available. Results Multimorbidity, assessed with the adjusted morbidity grouper, was the covariate with the highest impact in the predictive models, which in turn showed high performance measured by the C-statistics: (1) mortality (0.83), (2 and 3) hospitalisations (all causes: 0.77; COPD-related: 0.81), (4 and 5) multiple hospitalisations (all causes: 0.80; COPD-related: 0.87) and (6) users with high healthcare costs (0.76). Fifteen per cent of individuals with highest healthcare costs to year ratio represented 59% of the overall costs of patients with COPD. Conclusions The results stress the impact of assessing multimorbidity with the adjusted morbidity grouper on considered health indicators, which has implications for enhanced COPD staging and clinical management. Trial registration number NCT02956395. PMID:29511004

Return of the psychedelics: Psilocybin for treatment resistant depression.

PubMed

Patra, Suravi

2016-12-01

Psilocybin, the clinically most researched classic psychedelic has recently been tested for its safety and efficacy in a clinical population of treatment resistant depression. The efficacy of psilocybin in clinical depression previously demonstrated in the elecrophysiologic and neuroimaging findings as also in neuropsychological assessments is further validated by the findings of this rigorously conducted randomized trial. Mechanism of action of psilocybin and efficacy in treatment resistant depression are discussed in this paper. Ethical issues of conducting clinical trials with psychedelics are also discussed with particular emphasis on their relative safety and absence of addiction potential. Implications of these issues for conduct of larger trials for establishing risk benefit ratio in treatment resistant depression are further suggested. Copyright © 2016 Elsevier B.V. All rights reserved.

Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology.

PubMed

Schrijver, Iris; Aziz, Nazneen; Farkas, Daniel H; Furtado, Manohar; Gonzalez, Andrea Ferreira; Greiner, Timothy C; Grody, Wayne W; Hambuch, Tina; Kalman, Lisa; Kant, Jeffrey A; Klein, Roger D; Leonard, Debra G B; Lubin, Ira M; Mao, Rong; Nagan, Narasimhan; Pratt, Victoria M; Sobel, Mark E; Voelkerding, Karl V; Gibson, Jane S

2012-11-01

This report of the Whole Genome Analysis group of the Association for Molecular Pathology illuminates the opportunities and challenges associated with clinical diagnostic genome sequencing. With the reality of clinical application of next-generation sequencing, technical aspects of molecular testing can be accomplished at greater speed and with higher volume, while much information is obtained. Although this testing is a next logical step for molecular pathology laboratories, the potential impact on the diagnostic process and clinical correlations is extraordinary and clinical interpretation will be challenging. We review the rapidly evolving technologies; provide application examples; discuss aspects of clinical utility, ethics, and consent; and address the analytic, postanalytic, and professional implications. Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

The implications and applications of nanotechnology in dentistry: A review.

PubMed

AlKahtani, Rawan N

2018-04-01

The emerging science of nanotechnology, especially within the dental and medical fields, sparked a research interest in their potential applications and benefits in comparison to conventional materials used. Therefore, a better understanding of the science behind nanotechnology is essential to appreciate how these materials can be utilised in our daily practice. The present paper will help the reader understand nanoscience, and the benefits and limitations of nanotechnology by addressing its ethical, social, and health implications. Additionally, nano-applications in dental diagnostics, dental prevention, and in dental materials will be addressed, with examples of commercially available products and evidence on their clinical performance.

Holding on to hope: A review of the literature exploring missing persons, hope and ambiguous loss.

PubMed

Wayland, Sarah; Maple, Myfanwy; McKay, Kathy; Glassock, Geoffrey

2016-01-01

When a person goes missing, those left behind mourn an ambiguous loss where grief can be disenfranchised. Different to bereavement following death, hope figures into this experience as a missing person has the potential to return. This review explores hope for families of missing people. Lived experience of ambiguous loss was deconstructed to reveal responses punctuated by hope, which had practical and psychological implications for those learning to live with an unresolved absence. Future lines of enquiry must address the dearth of research exploring the role of hope, unresolved grief, and its clinical implications when a person is missing.

Tactile event-related potentials in amyotrophic lateral sclerosis (ALS): Implications for brain-computer interface.

PubMed

Silvoni, S; Konicar, L; Prats-Sedano, M A; Garcia-Cossio, E; Genna, C; Volpato, C; Cavinato, M; Paggiaro, A; Veser, S; De Massari, D; Birbaumer, N

2016-01-01

We investigated neurophysiological brain responses elicited by a tactile event-related potential paradigm in a sample of ALS patients. Underlying cognitive processes and neurophysiological signatures for brain-computer interface (BCI) are addressed. We stimulated the palm of the hand in a group of fourteen ALS patients and a control group of ten healthy participants and recorded electroencephalographic signals in eyes-closed condition. Target and non-target brain responses were analyzed and classified offline. Classification errors served as the basis for neurophysiological brain response sub-grouping. A combined behavioral and quantitative neurophysiological analysis of sub-grouped data showed neither significant between-group differences, nor significant correlations between classification performance and the ALS patients' clinical state. Taking sequential effects of stimuli presentation into account, analyses revealed mean classification errors of 19.4% and 24.3% in healthy participants and ALS patients respectively. Neurophysiological correlates of tactile stimuli presentation are not altered by ALS. Tactile event-related potentials can be used to monitor attention level and task performance in ALS and may constitute a viable basis for future BCIs. Implications for brain-computer interface implementation of the proposed method for patients in critical conditions, such as the late stage of ALS and the (completely) locked-in state, are discussed. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Echocardiography service provision in New Zealand: The implications of capacity modelling for the cardiac sonographer workforce.

PubMed

Buckley, Belinda; Farnworth, Mark J; Whalley, Gillian

2016-01-08

Regional disparity in both utilisation and the cardiac sonographer workforce has previously been identified. We sought to model the capacity of the cardiac sonographer workforce at a national and District Health Board level to better understand these regional differences. In 2013, surveys were distributed to 18 hospitals who employ cardiac sonographers (return rate 100%). Questions related to cardiac sonographer demographics, echo utilisation and workflow. Actual clinical capacity was calculated from scan duration and annual scan volumes. New Zealand national actual capacity was compared to predicted capacity from three international models. Potential clinical capacity was calculated from the workforce size in fulltime equivalent (FTE) and clinical availability. In New Zealand, scan duration and population-based clinical capacity varies between centres. The New Zealand capacity is similar to the UK 30:70 model, and consistently less than the US model for all scan types. There are marked regional differences in potential versus actual capacity, with 10/16 DHBs demonstrating excess potential capacity. There is regional disparity in the capacity of the cardiac sonographer workforce, which appears to be strongly related to scan duration. Workforce capacity modelling should be used with need and demand modelling to plan adequate levels of service provision.

The Subthalamic Nucleus, Limbic Function, and Impulse Control.

PubMed

Rossi, P Justin; Gunduz, Aysegul; Okun, Michael S

2015-12-01

It has been well documented that deep brain stimulation (DBS) of the subthalamic nucleus (STN) to address some of the disabling motor symptoms of Parkinson's disease (PD) can evoke unintended effects, especially on non-motor behavior. This observation has catalyzed more than a decade of research concentrated on establishing trends and identifying potential mechanisms for these non-motor effects. While many issues remain unresolved, the collective result of many research studies and clinical observations has been a general recognition of the role of the STN in mediating limbic function. In particular, the STN has been implicated in impulse control and the related construct of valence processing. A better understanding of STN involvement in these phenomena could have important implications for treating impulse control disorders (ICDs). ICDs affect up to 40% of PD patients on dopamine agonist therapy and approximately 15% of PD patients overall. ICDs have been reported to be associated with STN DBS. In this paper we will focus on impulse control and review pre-clinical, clinical, behavioral, imaging, and electrophysiological studies pertaining to the limbic function of the STN.

Estimating Preferences for Complex Health Technologies: Lessons Learned and Implications for Personalized Medicine.

PubMed

Marshall, Deborah A; Gonzalez, Juan Marcos; MacDonald, Karen V; Johnson, F Reed

2017-01-01

We examine key study design challenges of using stated-preference methods to estimate the value of whole-genome sequencing (WGS) as a specific example of genomic testing. Assessing the value of WGS is complex because WGS provides multiple findings, some of which can be incidental in nature and unrelated to the specific health concerns that motivated the test. In addition, WGS results can include actionable findings (variants considered to be clinically useful and can be acted on), findings for which evidence for best clinical action is not available (variants considered clinically valid but do not meet as high of a standard for clinical usefulness), and findings of unknown significance. We consider three key challenges encountered in designing our national study on the value of WGS-layers of uncertainty, potential downstream consequences with endogenous aspects, and both positive and negative utility associated with testing information-and potential solutions as strategies to address these challenges. We conceptualized the decision to acquire WGS information as a series of sequential choices that are resolved separately. To determine the value of WGS information at the initial decision to undergo WGS, we used contingent valuation questions, and to elicit respondent preferences for reducing risks of health problems and the consequences of taking the steps to reduce these risks, we used a discrete-choice experiment. We conclude by considering the implications for evaluating the value of other complex health technologies that involve multiple forms of uncertainty. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Best clinical trials reported in 2010.

PubMed

Garner, John B; Grayburn, Paul A; Yancy, Clyde W

2011-07-01

Each year, a number of clinical trials emerge with data sufficient to change clinical practice. Determining which findings will result in practice change and which will provide only incremental benefit can be a dilemma for clinicians. The authors review selected clinical trials reported in 2010 in journals, at society meetings, and at conferences, focusing on those studies that have the potential to change clinical practice. This review offers 3 separate means of analysis: an abbreviated text summary, organized by subject area; a comprehensive table of relevant clinical trials that provides a schematic review of the hypotheses, interventions, methods, primary end points, results, and implications; and a complete bibliography for further reading as warranted. It is hoped that this compilation of relevant clinical trials and their important findings released in 2010 will be of benefit in the everyday practice of cardiovascular medicine. Copyright © 2011 Elsevier Inc. All rights reserved.

Rational decision-making in mental health: the role of systematic reviews.

PubMed

Gilbody, Simon M.; Petticrew, Mark

1999-09-01

BACKGROUND: "Systematic reviews" have come to be recognized as the most rigorous method of summarizing confusing and often contradictory primary research in a transparent and reproducible manner. Their greatest impact has been in the summarization of epidemiological literature - particularly that relating to clinical effectiveness. Systematic reviews also have a potential to inform rational decision-making in healthcare policy and to form a component of economic evaluation. AIMS OF THE STUDY: This article aims to introduce the rationale behind systematic reviews and, using examples from mental health, to introduce the strengths and limitations of systematic reviews, particularly in informing mental health policy and economic evaluation. METHODS: Examples are selected from recent controversies surrounding the introduction of new psychiatric drugs (anti-depressants and anti-schizophrenia drugs) and methods of delivering psychiatric care in the community (case management and assertive community treatment). The potential for systematic reviews to (i) produce best estimates of clinical efficacy and effectiveness, (ii) aid economic evaluation and policy decision-making and (iii) highlight gaps in the primary research knowledge base are discussed. Lastly examples are selected from outside mental health to show how systematic reviews have a potential to be explicitly used in economic and health policy evaluation. RESULTS: Systematic reviews produce the best estimates of clinical efficacy, which can form an important component of economic evaluation. Importantly, serious methodological flaws and areas of uncertainty in the primary research literature are identified within an explicit framework. Summary indices of clinical effectiveness can be produced, but it is difficult to produce such summary indices of cost effectiveness by pooling economic data from primary studies. Modelling is commonly used in economic and policy evaluation. Here, systematic reviews can provide the best estimates of effectiveness and, importantly, highlight areas of uncertainty that can be used in "sensitivity analysis". DISCUSSION: Systematic reviews are an important recent methodological advance, the potential for which has only begun to be realized in mental health. This use of systematic reviews is probably most advanced in producing critical summaries of clinical effectiveness data. Systematic reviews cannot produce valid and believable conclusions when the primary research literature is of poor quality. An important function of systematic reviews will be in highlighting this poor quality research which is of little use in mental health decision making. IMPLICATIONS FOR HEALTH PROVISION: Health care provision should be both clinically and cost effective. Systematic reviews are a key component in ensuring that this goal is achieved. IMPLICATIONS FOR HEALTH POLICIES: Systematic reviews have potential to inform health policy. Examples presented show that health policy is often made without due consideration of the research evidence. Systematic reviews can provide robust and believable answers, which can help inform rational decision-making. Importantly, systematic reviews can highlight the need for important primary research and can inform the design of this research such that it provides answers that will help in forming healthcare policy. IMPLICATIONS FOR FURTHER RESEARCH: Systematic reviews should precede costly (and often unnecessary) primary research. Many areas of health policy and practice have yet to be evaluated using systematic review methodology. Methods for the summarization of economic data are methodologically complex and deserve further research

Globalisation as we enter the 21st century: reflections and directions for nursing education, science, research and clinical practice.

PubMed

Davidson, Patricia M; Meleis, Afaf; Daly, John; Douglas, Marilyn Marty

2003-10-01

The events of September 11th, 2001 in the United States and the Bali bombings of October 2002 are chastening examples of the entangled web of the religious, political, health, cultural and economic forces we experience living in a global community. To view these forces as independent, singular, linearly deterministic entities of globalisation is irrational and illogical. Understanding the concept of globalisation has significant implications not only for world health and international politics, but also the health of individuals. Depending on an individual's political stance and world-view, globalisation may be perceived as an emancipatory force, having the potential to bridge the chasm between rich and poor or, in stark contrast, the very essence of the divide. It is important that nurses appreciate that globalisation does not pertain solely to the realms of economic theory and world politics, but also that it impacts on our daily nursing practice and the welfare of our patients. Globalisation and the closer interactions of human activity that result, have implications for international governance, policy and theory development as well as nursing education, research and clinical practice. Nurses, individually and collectively, have the political power and social consciousness to influence the forces of globalisation to improve health for all. This paper defines and discusses globalisation in today's world and its implications for contemporary nursing education, science, research and clinical practice.

Ethical, Legal, Social, and Policy Implications of Behavioral Genetics

PubMed Central

Berryessa, Colleen M.; Cho, Mildred K.

2015-01-01

The field of behavioral genetics has engendered a host of moral and social concerns virtually since its inception. The policy implications of a genetic basis for behaviors are widespread and extend beyond the clinic to the socially important realms of education, criminal justice, childbearing, and child rearing. The development of new techniques and analytic approaches, including whole-genome sequencing, noninvasive prenatal genetic testing, and optogenetics, has clearly changed the study of behavioral genetics. However, the social context of biomedical research has also changed profoundly over the past few decades, and in ways that are especially relevant to behavioral genetics. The ever-widening scope of behavioral genetics raises ethical, legal, social, and policy issues in the potential new applications to criminal justice, education, the military, and reproduction. These issues are especially critical to address because of their potentially disproportionate effects on vulnerable populations such as children, the unborn, and the incarcerated. PMID:23452225

Familism and Health Care Provision to Hispanic Older Adults.

PubMed

Savage, Brittany; Foli, Karen J; Edwards, Nancy E; Abrahamson, Kathleen

2016-01-01

The Hispanic older adult population's rapid growth calls for an awareness of values that can affect the rendering and receipt of care. Familism, or familismo, a traditional Hispanic value, places importance of family over the self and can potentially affect health care perceptions and practices for Hispanic older adults. The current article discusses familism, which is upheld by some Hispanic older adults, and the potential for underuse of health care services. The traditional feminine role, marianismo, and masculine role, machismo, are considered, as well as implications for how decision making may be made by family members rather than the patient. Clinical implications for the provision of health care to Hispanic older adults are provided, along with the importance of considering acculturation and ethnic heterogeneity. Health care management strategies that reflect recognition and respect of familism, yet emphasize optimization of adherence and self-care, are described. Copyright 2016, SLACK Incorporated.

Cocoa and cardiovascular health.

PubMed

Corti, Roberto; Flammer, Andreas J; Hollenberg, Norman K; Lüscher, Thomas F

2009-03-17

Epidemiological data demonstrate that regular dietary intake of plant-derived foods and beverages reduces the risk of coronary heart disease and stroke. Among many ingredients, cocoa might be an important mediator. Indeed, recent research demonstrates a beneficial effect of cocoa on blood pressure, insulin resistance, and vascular and platelet function. Although still debated, a range of potential mechanisms through which cocoa might exert its benefits on cardiovascular health have been proposed, including activation of nitric oxide and antioxidant and antiinflammatory effects. This review summarizes the available data on the cardiovascular effects of cocoa, outlines potential mechanisms involved in the response to cocoa, and highlights the potential clinical implications associated with its consumption.

Emergence of molecular imaging of aortic aneurysm; implications for risk stratification and management

PubMed Central

Golestani, Reza; Sadeghi, Mehran M.

2014-01-01

Summary Imaging cellular and molecular processes associated with aneurysm expansion, dissection, and rupture can potentially transform the management of patients with thoracic and abdominal aortic aneurysm (TAA and AAA). Here, we review recent advances in molecular imaging of aortic aneurysm, focusing on imaging modalities with the greatest potential for clinical translation and application, PET, SPECT and MRI. Inflammation (e.g., with 18F-FDG, nanoparticles) and matrix remodeling (e.g., with matrix metalloproteinase-targeted tracers) are highlighted as promising targets for molecular imaging of aneurysm. Potential alternative or complementary approaches to molecular imaging for aneurysm risk stratification are briefly discussed. PMID:24381115

The role of air pollution in COPD and implications for therapy.

PubMed

Lopez-Campos, J L; Marquez-Martin, E; Soriano, J B

2016-08-01

Exposure to many environmental conditions, apart from tobacco, as a risk factor for developing chronic obstructive pulmonary disease (COPD) has been comprehensively studied. Global estimates of air pollution depict a scenario of a considerable burden on respiratory health. Exposure to biomass smoke and occupational inhaled agents have been described as potentially related to causing or aggravating COPD. A number of emerging natural or accidental disasters have been suggested as a new source of exposure. Management of COPD patients exposed to different substances should include avoidance, especially in the more susceptible populations and proper pharmacological treatment considering potential association with particular clinical presentations. Expert commentary: Altogether, the available information indicates that appraisal of different environmental pollution exposures is clinically relevant, and should be systematically evaluated in COPD.

Contrasting Medical and Legal Standards of Evidence: A Precision Medicine Case Study

PubMed Central

Marchant, Gary E.; Scheckel, Kathryn; Campos-Outcalt, Doug

2016-01-01

Precis As the health care system transitions to a precision medicine approach that tailors clinical care to the genetic profile of the individual patient, there is a potential tension between the clinical uptake of new technologies by providers and the legal system’s expectation of the standard of care in applying such technologies. We examine this tension by comparing the type of evidence that physicians and courts are likely to rely on in determining a duty to recommend pharmacogenetic testing of patients prescribed the oral anti-coagulant drug warfarin. There is a large body of inconsistent evidence and factors for and against such testing, but physicians and courts are likely to weigh this evidence differently. The potential implications for medical malpractice risk are evaluated and discussed. PMID:27256135

The future implications and indications of anti-vascular endothelial growth factor therapy in ophthalmic practice

PubMed Central

Ghanekar, Yashoda; Kaur, Inderjeet

2007-01-01

In the last few years anti-vascular endothelial growth factor (VEGF) therapy has changed the paradigm in the treatment of neovascular age-related macular degeneration (ARMD). Besides, its potential use in the treatment of diabetic retinopathy and other possible proliferative vascular disorders has also shown promise. Clinical trial results have shown tremendous beneficial effect of ranibizumab in ARMD. Off-label use of bevacizumab has also shown similar benefit but long-term and clinical trial results do not exist. Some of the potential questions in the use of anti-VEGF are recurring cost, possible long-term effect on physiological function of VEGF and determination of endpoint of treatment. Overall, the use of anti-VEGF therapy in ocular angiogenesis has proven to be beneficial at least now. PMID:17951902

Exercise and physical activity in mental disorders: clinical and experimental evidence.

PubMed

Zschucke, Elisabeth; Gaudlitz, Katharina; Ströhle, Andreas

2013-01-01

Several epidemiological studies have shown that exercise (EX) and physical activity (PA) can prevent or delay the onset of different mental disorders, and have therapeutic benefits when used as sole or adjunct treatment in mental disorders. This review summarizes studies that used EX interventions in patients with anxiety, affective, eating, and substance use disorders, as well as schizophrenia and dementia/mild cognitive impairment. Despite several decades of clinical evidence with EX interventions, controlled studies are sparse in most disorder groups. Preliminary evidence suggests that PA/EX can induce improvements in physical, subjective and disorder-specific clinical outcomes. Potential mechanisms of action are discussed, as well as implications for psychiatric research and practice.

Unusual Aetiology of Pasteurella canis Biovar 2 Causing Dacryocystitis in HIV Patient: A Case Report and Review of Literature

PubMed Central

Negi, Sanjay Singh; Gade, Neeta

2017-01-01

Pasteurella species are zoonotic bacterial pathogens implicated very infrequently in various human infections following animal bites or licks usually of dogs and cats. This case report described a rare clinical presentation of dacryocystitis caused by P.canis in a Human Immunodeficiency Virus (HIV) positive young male patient involved in caring of cattle. It advocates the utmost need of recognizing the wide clinical manifestation spectrum of P.canis even without prior penetrating injury. P.canis associated clinical infection is more extensive than had been thought previously especially in immunocompromised patient. Early accurate identification and evidence based anti-microbial therapy may prove crucial in preventing further potential complications. PMID:28384864

Targeting a Common Collaborator in Cancer Development

PubMed Central

Myers, Andrea P.; Cantley, Lewis C.

2012-01-01

In this issue of Science Translational Medicine, Wallin et al. have identified a subset of breast and ovarian cancer cell lines that show synergistic response to the combination of doxorubicin and GDC-0941, a class IA phosphatidylinositol 3-kinase (PI3K) inhibitor. Here, we discuss the potential implications of these data on the clinical development of PI3K pathway inhibitors as cancer therapeutics. PMID:20826838

From Anatomical "Competence" to Complex Capability. The Views and Experiences of UK Tutors on How We Should Teach Anatomy to Medical Students

ERIC Educational Resources Information Center

de Bere, Sam Regan; Mattick, Karen

2010-01-01

Developments in clinical education have recently challenged the identity of anatomy teaching and learning, leading to high profile debate over the potential implications for the competence levels of new doctors. However, the emphasis remains on methods of teaching, rather than a review of what well-rounded anatomical learning actually entails, and…

Interlaboratory discrepancy of antigenuria results in 2 patients with AIDS and histoplasmosis.

PubMed

McKinsey, David S; McKinsey, Joel P; Northcutt, Noelle; Sarria, Juan C

2009-01-01

Histoplasma polysaccharide antigen testing is used routinely to diagnose histoplasmosis. At least 3 antigen tests are commercially available. Controversy exists about the relative accuracy of these tests. We report 2 patients with AIDS and culture-confirmed Histoplasma capsulatum meningitis from whom discrepant Histoplasma polysaccharide antigen results were obtained from different laboratories and discuss the potential clinical implications of these results.

TCGA divides gastric cancer into four molecular subtypes: implications for individualized therapeutics.

PubMed

Zhang, Wei

2014-10-01

Gastric cancer is a leading cause of cancer deaths in the world. The treatment of gastric cancer is challenging because of its highly heterogeneous etiology and clinical characteristics. Recent genomic and molecular characterization of gastric cancer, especially the findings reported by the Cancer Genome Atlas (TCGA), have shed light on the heterogeneity and potential targeted therapeutics for four different subtypes of gastric cancer.

Personalized ophthalmology.

PubMed

Porter, L F; Black, G C M

2014-07-01

Ophthalmology has been an early adopter of personalized medicine. Drawing on genomic advances to improve molecular diagnosis, such as next-generation sequencing, and basic and translational research to develop novel therapies, application of genetic technologies in ophthalmology now heralds development of gene replacement therapies for some inherited monogenic eye diseases. It also promises to alter prediction, diagnosis and management of the complex disease age-related macular degeneration. Personalized ophthalmology is underpinned by an understanding of the molecular basis of eye disease. Two important areas of focus are required for adoption of personalized approaches: disease stratification and individualization. Disease stratification relies on phenotypic and genetic assessment leading to molecular diagnosis; individualization encompasses all aspects of patient management from optimized genetic counseling and conventional therapies to trials of novel DNA-based therapies. This review discusses the clinical implications of these twin strategies. Advantages and implications of genetic testing for patients with inherited eye diseases, choice of molecular diagnostic modality, drivers for adoption of personalized ophthalmology, service planning implications, ethical considerations and future challenges are considered. Indeed, whilst many difficulties remain, personalized ophthalmology truly has the potential to revolutionize the specialty. © 2014 The Authors. Clinical Genetics published by JohnWiley & Sons A/S. Published by John Wiley & Sons Ltd.

The practice and clinical implications of tablet splitting in international health

PubMed Central

Elliott, Ivo; Mayxay, Mayfong; Yeuichaixong, Sengchanh; Lee, Sue J; Newton, Paul N

2014-01-01

Objective Tablet splitting is frequently performed to facilitate correct dosing, but the practice and implications in low-income settings have rarely been discussed. Methods We selected eight drugs, with narrow therapeutic indices or critical dosages, frequently divided in the Lao PDR (Laos). These were split, by common techniques used in Laos, by four nurses and four laypersons. The mean percentage deviation from the theoretical expected weight and weight loss of divided tablets/capsules were recorded. Results Five of eight study drugs failed, on splitting, to meet European Pharmacopoeia recommendations for tablet weight deviation from the expected weight of tablet/capsule halves with 10% deviating by more than 25%. There was a significant difference in splitting accuracy between nurses and laypersons (P = 0.027). Coated and unscored tablets were less accurately split than uncoated (P = 0.03 and 0.0019 for each half) and scored (0.0001 for both halves) tablets. Conclusion These findings have potential clinical implications on treatment outcome and the development of antimicrobial resistance. Investment by drug companies in a wider range of dosage units, particularly for narrow therapeutic index and critical dosage medicines, is strongly recommended. PMID:24702766

The National Health Service Knowledge and Skills Framework and its implications for continuing professional development in nursing.

PubMed

Gould, Dinah; Berridge, Emma-Jane; Kelly, Daniel

2007-01-01

The National Health Service Knowledge and Skills Framework has been introduced as part of the Agenda for Change Reforms in the United Kingdom to link pay and career progression to competency. The purpose of this paper is to consider the implications for nurses, their managers and the impact on university departments delivering continuing professional development for nurses. The new system has the potential to increase the human resources management aspect of the clinical nurse managers' role and could have legal implications, for example if practitioners perceive that their needs for continuing professional development have been overlooked to the detriment of their pay and career aspirations. The new system also has implications for providers of continuing professional development in the universities and is likely to demand closer liaison between education providers and trust staff who commission education and training. The Knowledge and Skills Framework is of interest to nurses and nurse educators internationally because the system, if effective, could be introduced elsewhere.

Evidence for social working memory from a parametric functional MRI study.

PubMed

Meyer, Meghan L; Spunt, Robert P; Berkman, Elliot T; Taylor, Shelley E; Lieberman, Matthew D

2012-02-07

Keeping track of various amounts of social cognitive information, including people's mental states, traits, and relationships, is fundamental to navigating social interactions. However, to date, no research has examined which brain regions support variable amounts of social information processing ("social load"). We developed a social working memory paradigm to examine the brain networks sensitive to social load. Two networks showed linear increases in activation as a function of increasing social load: the medial frontoparietal regions implicated in social cognition and the lateral frontoparietal system implicated in nonsocial forms of working memory. Of these networks, only load-dependent medial frontoparietal activity was associated with individual differences in social cognitive ability (trait perspective-taking). Although past studies of nonsocial load have uniformly found medial frontoparietal activity decreases with increasing task demands, the current study demonstrates these regions do support increasing mental effort when such effort engages social cognition. Implications for the etiology of clinical disorders that implicate social functioning and potential interventions are discussed.

The Mental Capacity Act 2005: implications for dietetic practice.

PubMed

Lyons, C; Brotherton, A; Stanley, N; Carrahar, M; Manthorpe, J

2007-08-01

The Mental Capacity Act (MCA) 2005 will be implemented in England and Wales in 2007 and have consequences for dietitians who work with people who may lack capacity to make specific decisions. This paper will explore issues arising from the introduction of the Act and considers the implications for dietitians involved in the delivery of clinical care, using enteral feeding as an illustrative example. If patients lack capacity to make specific decisions, dietitians will be required to record if, how and why they reached a decision, how they are involved in the decision making process and need to be able to justify their actions in relation to those decisions. This paper discusses the importance of dietitians' involvement in best interests decision making and considers the implications of decision making where people have drawn up a Lasting Power of Attorney. The role of such advance decisions is discussed and consideration is given to the potential compatibility of perspectives between the patient and family that may give rise to disputes. Dietitians may be well placed within multidisciplinary team working to ensure patients and their carers are part of the decision making process through effective communication and support for patients. Dietitians in England and Wales must consider the implications of the MCA upon their clinical practice and others outside these jurisdictions may like to reflect on the relevance of such developments in their own contexts.

Video game addiction: Impact on teenagers' lifestyle.

PubMed

Sharma, Manoj Kumar; Mahindru, Poornima

2015-01-01

Use of video games as a leisure-time activity has increased among teenagers. Excessive use of video games is associated with psychosocial dysfunctions in the user's life. Two teenagers came for consultation to our Service for Healthy Use of Technology (SHUT) clinic for management of addiction due to video games. They were assessed using a clinical interview as well as the General Health Questionnaire and Griffith criteria for video games. The cases emphasize the addictive potential of video games and their association with lifestyle changes. Addiction to video games has implications for screening and intervention among teenagers. Copyright 2015, NMJI.

Integrating research, clinical care, and education in academic health science centers.

PubMed

King, Gillian; Thomson, Nicole; Rothstein, Mitchell; Kingsnorth, Shauna; Parker, Kathryn

2016-10-10

Purpose One of the major issues faced by academic health science centers (AHSCs) is the need for mechanisms to foster the integration of research, clinical, and educational activities to achieve the vision of evidence-informed decision making (EIDM) and optimal client care. The paper aims to discuss this issue. Design/methodology/approach This paper synthesizes literature on organizational learning and collaboration, evidence-informed organizational decision making, and learning-based organizations to derive insights concerning the nature of effective workplace learning in AHSCs. Findings An evidence-informed model of collaborative workplace learning is proposed to aid the alignment of research, clinical, and educational functions in AHSCs. The model articulates relationships among AHSC academic functions and sub-functions, cross-functional activities, and collaborative learning processes, emphasizing the importance of cross-functional activities in enhancing collaborative learning processes and optimizing EIDM and client care. Cross-functional activities involving clinicians, researchers, and educators are hypothesized to be a primary vehicle for integration, supported by a learning-oriented workplace culture. These activities are distinct from interprofessional teams, which are clinical in nature. Four collaborative learning processes are specified that are enhanced in cross-functional activities or teamwork: co-constructing meaning, co-learning, co-producing knowledge, and co-using knowledge. Practical implications The model provides an aspirational vision and insight into the importance of cross-functional activities in enhancing workplace learning. The paper discusses the conceptual and empirical basis to the model, its contributions and limitations, and implications for AHSCs. Originality/value The model's potential utility for health care is discussed, with implications for organizational culture and the promotion of cross-functional activities.

Clinical and Economic Implications of AF Related Stroke.

PubMed

Ali, Ali N; Abdelhafiz, Ahmed

2016-01-01

A major cause of morbidity and mortality among patients with atrial fibrillation (AF) relates to the increased risk of stroke. The burden of illness that AF imparts on stroke is likely to increase with our aging populations and increasingly sophisticated cardiac monitoring techniques. Understanding the clinical and economic differences between AF related ischaemic stroke and non-AF related stroke is important if we are to improve future cost effectiveness analyses of potential preventative treatments, but also to help educate clinical and policy decision makers on use or availability of treatments to prevent AF related stroke. In this article we review the existing evidence that highlights differences in the clinical characteristics and outcomes between AF and non-AF stroke, as well as differences in their economic impact and discuss ways to improve future economic analyses.

Non-invasive prenatal testing for single gene disorders: exploring the ethics.

PubMed

Deans, Zuzana; Hill, Melissa; Chitty, Lyn S; Lewis, Celine

2013-07-01

Non-invasive prenatal testing for single gene disorders is now clearly on the horizon. This new technology offers obvious clinical benefits such as safe testing early in pregnancy. Before widespread implementation, it is important to consider the possible ethical implications. Four hypothetical scenarios are presented that highlight how ethical ideals of respect for autonomy, privacy and fairness may come into play when offering non-invasive prenatal testing for single gene disorders. The first scenario illustrates the moral case for using these tests for 'information only', identifying a potential conflict between larger numbers of women seeking the benefits of the test and the wider social impact of funding tests that do not offer immediate clinical benefit. The second scenario shows how the simplicity and safety of non-invasive prenatal testing could lead to more autonomous decision-making and, conversely, how this could also lead to increased pressure on women to take up testing. In the third scenario we show how, unless strong safeguards are put in place, offering non-invasive prenatal testing could be subject to routinisation with informed consent undermined and that woman who are newly diagnosed as carriers may be particularly vulnerable. The final scenario introduces the possibility of a conflict of the moral rights of a woman and her partner through testing for single gene disorders. This analysis informs our understanding of the potential impacts of non-invasive prenatal testing for single gene disorders on clinical practice and has implications for future policy and guidelines for prenatal care.

Risk of type 1 diabetes progression in islet autoantibody-positive children can be further stratified using expression patterns of multiple genes implicated in peripheral blood lymphocyte activation and function.

PubMed

Jin, Yulan; Sharma, Ashok; Bai, Shan; Davis, Colleen; Liu, Haitao; Hopkins, Diane; Barriga, Kathy; Rewers, Marian; She, Jin-Xiong

2014-07-01

There is tremendous scientific and clinical value to further improving the predictive power of autoantibodies because autoantibody-positive (AbP) children have heterogeneous rates of progression to clinical diabetes. This study explored the potential of gene expression profiles as biomarkers for risk stratification among 104 AbP subjects from the Diabetes Autoimmunity Study in the Young (DAISY) using a discovery data set based on microarray and a validation data set based on real-time RT-PCR. The microarray data identified 454 candidate genes with expression levels associated with various type 1 diabetes (T1D) progression rates. RT-PCR analyses of the top-27 candidate genes confirmed 5 genes (BACH2, IGLL3, EIF3A, CDC20, and TXNDC5) associated with differential progression and implicated in lymphocyte activation and function. Multivariate analyses of these five genes in the discovery and validation data sets identified and confirmed four multigene models (BI, ICE, BICE, and BITE, with each letter representing a gene) that consistently stratify high- and low-risk subsets of AbP subjects with hazard ratios >6 (P < 0.01). The results suggest that these genes may be involved in T1D pathogenesis and potentially serve as excellent gene expression biomarkers to predict the risk of progression to clinical diabetes for AbP subjects. © 2014 by the American Diabetes Association.

Recent advances in the pathophysiology of arterial hypertension: potential implications for clinical practice.

PubMed

Hering, Dagmara; Trzebski, Andrzej; Narkiewicz, Krzysztof

2017-03-01

Hypertension remains a major and growing public health problem associated with the greatest global rate of cardiovascular morbidity and mortality. Although numerous factors contribute to poor control of blood pressure (BP) and to pseudoresistance (eg, unawareness, lifestyle habits, nonadherence to medication, insufficient treatment, drug‑induced hypertension, undiagnosed secondary causes), true resistant hypertension (RH) is reported in 10.1% of patients treated for elevated BP. While the mechanisms underlying RH remain complex and not entirely understood, sympathetic activation involved in the pathophysiology of hypertension, disease progression, and adverse complications is further augmented in patients with drug‑resistant hypertension. The well‑established contribution of neurogenic component of hypertension has led to the introduction of new alternative therapies aimed specifically at modulating central and neural reflexes mechanisms involved in BP control. Although clinical benefits of lowering BP with renal denervation, baroreflex activation therapy, carotid body denervation, central arteriovenous anastomosis, and deep brain stimulation have advanced our knowledge on uncontrolled hypertension, the variable BP response has prompted extensive ongoing research to define predictors of treatment effectiveness and further investigation of pathophysiology of RH. Very recently, research on the role of vasopressinergic neurons, masked tachycardia, and impaired brain neural activity has provided novel insights into hypertension. This review briefly summarizes the role of the centrally mediated sympathetic nervous system in hypertension, the therapeutic strategies that distinctively target impaired neural reflex mechanisms, and potential implications for future clinical research and therapies.

Gonadal dysfunction in men with chronic kidney disease: clinical features, prognostic implications and therapeutic options.

PubMed

Iglesias, Pedro; Carrero, Juan J; Díez, Juan J

2012-01-01

Gonadal dysfunction is a frequent finding in men with chronic kidney disease and with end-stage renal disease. Testosterone deficiency, usually accompanied by elevation of serum gonadotropin concentrations, is present in 26-66% of men with different degrees of renal failure. Uremia-associated hypogonadism is multifactorial in its origin, and rarely improves with initiation of dialysis, although it usually normalizes after renal transplantation. Experimental and clinical evidence suggests that testosterone may have important clinical implications with regards to kidney disease progression, derangements in sexual drive, libido and erectile dysfunction, development of anemia, impairment of muscle mass and strength, and also progression of atherosclerosis and cardiovascular disease. Additionally, low testosterone levels in hemodialysis patients have been associated with increased mortality risk in some studies. Currently, we count with available therapeutic options in the management of uremic hypogonadism, from optimal delivery of dialysis and adequate nutritional intake, to hormone replacement therapy with different testosterone preparations. Other potential options for treatment include the use of antiestrogens, dopamine agonists, erythropoiesis-stimulating factors, vitamins, essential trace elements, chorionic gonadotropin and renal transplantation. Potential adverse effects of androgen replacement therapy in patients with kidney disease comprise, however, erythrocytosis, prostate and breast cancer growth, reduced fertility, gynecomastia, obstructive sleep apnea and fluid retention. Androgen preparations should be used with caution with stringent monitoring in uremic men. Although there are encouraging data suggesting plausible benefits from testosterone replacement therapy, further studies are needed with regards to safety and effectiveness of this therapy.

Clinical Ethics Consultation After God: Implications for Advocacy and Neutrality.

PubMed

Parker, J Clint

2018-06-01

In After God: Morality and Bioethics in a Secular Age, H. Tristram Engelhardt, Jr. explores the broad implications for moral reasoning once a culture has lost a God's-eye perspective. In this paper, I focus on the implications of Engelhardt's views for clinical ethics consultation. I begin by examining the question of whether clinical ethics consultants (CECs) should advocate a particular viewpoint and/or process during consultations or adopt a neutral stance. I then examine the implications of Engelhardt's views for this question. Finally, I discuss some of Engelhardt's foundational ontological, metaphysical, meta-ethical, and epistemological commitments and how these commitments connect to his views on clinical ethics consultation.

Fluctuations in the emotional intelligence of therapy students during clinical placements: Implication for educators, supervisors, and students.

PubMed

Gribble, Nigel; Ladyshewsky, Richard K; Parsons, Richard

2017-01-01

This study investigated the changes in emotional intelligence (EI) of occupational therapy, physiotherapy, and speech pathology students (therapy students). Clinical placements have multiple benefits including the development of interprofessional skills, enhancing practice skills and interpersonal skills. Higher EI competencies have been shown to have a positive impact on patient outcomes, teamwork skills, dealing with stress, and patient satisfaction. Data for this study were collected at two time points: before third-year therapy students commenced extended clinical placements (T1 with 261 students) and approximately 7 months later after students had completed one or more clinical placements (T2 with 109 students). EI was measured using the Emotional Quotient Inventory 2.0 (EQ-i 2.0 ). Only one EI score, assertiveness, demonstrated a significant decline. No EI score showed a significant increase. A third or more of the students showed increases of five points or more in self-actualisation, emotional expression, independence, reality testing and optimism. However, of concern were the five EI scores where therapy students' EI scores decreased by more than five points: assertiveness (where 38% of students declined), problem solving (37%), impulse control (35%), self-actualisation (35%), and stress tolerance (33%). With EI scores declining for some students during clinical placements, there are implications for clinical supervisors and interprofessional facilitators as clinical performance may decline concurrently. There is a range of potential reasons that clinical placements could negatively influence the EI competencies of a therapy student, including poor clinical supervision, conflict between a student, and supervisor and failing a clinical placement. The research suggests that interprofessional facilitators and university educators might consider students undertaking EI tests before clinical placements.

Preprocessing Structured Clinical Data for Predictive Modeling and Decision Support

PubMed Central

Oliveira, Mónica Duarte; Janela, Filipe; Martins, Henrique M. G.

2016-01-01

Summary Background EHR systems have high potential to improve healthcare delivery and management. Although structured EHR data generates information in machine-readable formats, their use for decision support still poses technical challenges for researchers due to the need to preprocess and convert data into a matrix format. During our research, we observed that clinical informatics literature does not provide guidance for researchers on how to build this matrix while avoiding potential pitfalls. Objectives This article aims to provide researchers a roadmap of the main technical challenges of preprocessing structured EHR data and possible strategies to overcome them. Methods Along standard data processing stages – extracting database entries, defining features, processing data, assessing feature values and integrating data elements, within an EDPAI framework –, we identified the main challenges faced by researchers and reflect on how to address those challenges based on lessons learned from our research experience and on best practices from related literature. We highlight the main potential sources of error, present strategies to approach those challenges and discuss implications of these strategies. Results Following the EDPAI framework, researchers face five key challenges: (1) gathering and integrating data, (2) identifying and handling different feature types, (3) combining features to handle redundancy and granularity, (4) addressing data missingness, and (5) handling multiple feature values. Strategies to address these challenges include: cross-checking identifiers for robust data retrieval and integration; applying clinical knowledge in identifying feature types, in addressing redundancy and granularity, and in accommodating multiple feature values; and investigating missing patterns adequately. Conclusions This article contributes to literature by providing a roadmap to inform structured EHR data preprocessing. It may advise researchers on potential pitfalls and implications of methodological decisions in handling structured data, so as to avoid biases and help realize the benefits of the secondary use of EHR data. PMID:27924347

Genetics of pancreatic neuroendocrine tumors: implications for the clinic

PubMed Central

Pea, Antonio; Hruban, Ralph H.; Wood, Laura D.

2016-01-01

Pancreatic neuroendocrine tumors (PanNETs) are a common and deadly neoplasm of the pancreas. Although the importance of genetic alterations in PanNETs has been known for many years, recent comprehensive sequencing studies have greatly expanded our knowledge of neuroendocrine tumorigenesis in the pancreas. These studies have identified specific cellular processes that are altered in PanNETs, highlighted alterations with prognostic implications, and pointed to pathways for targeted therapies. In this review, we will discuss the genetic alterations that play a key role in PanNET tumorigenesis, with a specific focus on those alterations with the potential to change the way patients with these neoplasms are diagnosed and treated. PMID:26413978

An immunotherapeutic treatment against flea allergy dermatitis in cats by co-immunization of DNA and protein vaccines.

PubMed

Jin, Jin; Ding, Zheng; Meng, Fengxia; Liu, Qiyong; Ng, Terry; Hu, Yanxin; Zhao, Gan; Zhai, Bing; Chu, Hsien-Jue; Wang, Bin

2010-02-23

Flea allergy dermatitis (FAD) is considered a harmful and persistent allergic disease in cats, dogs and humans. Effective and safe antigen-specific treatments are lacking. Previously we reported that the simultaneous co-immunization with a DNA vaccine and its cognate coded protein antigen could induce antigen-specific iTreg cells (inducible Treg cells); demonstrating its potential to protect animals from FAD in a murine model. Its clinical efficacy however, remains to be demonstrated. In this report, we clinically tested this protocol to treat established FAD in cats following flea infestations. We present data showing a profound therapeutic improvement of dermatitis in these FAD cats following two co-immunizations, not only in relieving clinical symptoms, but also the amelioration of the allergic responses, including antigen-induced wheal formation, elevated T cell proliferation, infiltration of lymphocytes and migration of mast cells to the sites. This study demonstrates that a co-immunization approach as described can be used to treat flea-induced allergic disease in animals, thus implicating its potential for a practical clinical application. Copyright 2009 Elsevier Ltd. All rights reserved.

Inappropriate publication of trial results and potential for allegations of illegal share dealing.

PubMed

Freestone, D S; Mitchell, H

1993-04-24

There is increasing evidence of fraud in clinical research, and one aspect concerns trading in pharmaceutical company shares by people who may have confidential information about the results of clinical trials. Plainly this has implications for honest investigators, who may find themselves exposed to such allegations. In this paper Dr D S Freestone and Mr H Mitchell, QC, identify three interlinked issues which they think underlie the potential for these allegations. They are pressure for premature or inappropriate communication of research results; trading in pharmaceutical company shares by academic clinical investigators; and the possibility that clinical investigators might succumb to temptation. Dr Freestone and Mr Mitchell suggest that whenever possible results of clinical studies should be published in appropriate medical journals without prior public disclosure. This conflicts with Stock Exchange rules, which require that price sensitive information should be published at the earliest opportunity and preclude priority of publication in medical journals. Freestone and Mitchell believe that rarely rapid public disclosure is acceptable if it is to protect patients' interests but that it must not prejudice publication in the medical or scientific press. When rapid public disclosure is needed, they say, every attempt should be made to inform prescribers before patients. Dr Freestone and Mr Mitchell warn that academic clinical investigators who have access to unpublished price sensitive information about pharmaceutical companies whose shares they trade in will almost certainly be in breach of the Company Securities (Insider Dealing) Act 1985. Furthermore, disclosing such information to third parties, they say, exposes those people also to potential criminal liability. Freestone and Mitchell advise that when potential for allegations of conflict of interest exists clinical investigators should consider declaring their position to ethics committees and any sponsoring organisations.

Inappropriate publication of trial results and potential for allegations of illegal share dealing.

PubMed Central

Freestone, D S; Mitchell, H

1993-01-01

There is increasing evidence of fraud in clinical research, and one aspect concerns trading in pharmaceutical company shares by people who may have confidential information about the results of clinical trials. Plainly this has implications for honest investigators, who may find themselves exposed to such allegations. In this paper Dr D S Freestone and Mr H Mitchell, QC, identify three interlinked issues which they think underlie the potential for these allegations. They are pressure for premature or inappropriate communication of research results; trading in pharmaceutical company shares by academic clinical investigators; and the possibility that clinical investigators might succumb to temptation. Dr Freestone and Mr Mitchell suggest that whenever possible results of clinical studies should be published in appropriate medical journals without prior public disclosure. This conflicts with Stock Exchange rules, which require that price sensitive information should be published at the earliest opportunity and preclude priority of publication in medical journals. Freestone and Mitchell believe that rarely rapid public disclosure is acceptable if it is to protect patients' interests but that it must not prejudice publication in the medical or scientific press. When rapid public disclosure is needed, they say, every attempt should be made to inform prescribers before patients. Dr Freestone and Mr Mitchell warn that academic clinical investigators who have access to unpublished price sensitive information about pharmaceutical companies whose shares they trade in will almost certainly be in breach of the Company Securities (Insider Dealing) Act 1985. Furthermore, disclosing such information to third parties, they say, exposes those people also to potential criminal liability. Freestone and Mitchell advise that when potential for allegations of conflict of interest exists clinical investigators should consider declaring their position to ethics committees and any sponsoring organisations. Images p1113-a p1114-a PMID:8495159

Technology, design and dementia: an exploratory survey of developers.

PubMed

Jiancaro, Tizneem; Jaglal, Susan B; Mihailidis, Alex

2017-08-01

Despite worldwide surges in dementia, we still know relatively little about the design of home technologies that support this population. The purpose of this study was to investigate design considerations from the perspective of developers. Participants, including technical and clinical specialists, were recruited internationally and answered web-based survey questions comprising Likert-type responses with text entry options. Developers were queried on 23 technology acceptance characteristics and 24 design practices. In all, forty developers completed the survey. Concerning "technology acceptance", cost, learnability, self-confidence (during use) and usability were deemed very important. Concerning "design practice", developers overwhelmingly valued user-centred design (UCD). In terms of general assistive technology (AT) models, these were largely unknown by technical specialists compared to clinical specialists. Recommendations based on this study include incorporating "self-confidence" into design protocols; examining the implications of "usability" and UCD in this context; and considering empathy-based design approaches to suit a diverse user population. Moreover, clinical specialists have much to offer development teams, particularly concerning the use of conceptual AT models. Implications of rehabilitation Stipulate precise usability criteria. Consider "learnability" and "self-confidence" as technology adoption criteria. Recognize the important theoretical role that clinical specialists can fulfil concerning the use of design schemas. Acknowledge the diversity amongst users with dementia, potentially adopting techniques, such as designing for "extraordinary users".

Rapid-Learning System for Cancer Care

PubMed Central

Abernethy, Amy P.; Etheredge, Lynn M.; Ganz, Patricia A.; Wallace, Paul; German, Robert R.; Neti, Chalapathy; Bach, Peter B.; Murphy, Sharon B.

2010-01-01

Compelling public interest is propelling national efforts to advance the evidence base for cancer treatment and control measures and to transform the way in which evidence is aggregated and applied. Substantial investments in health information technology, comparative effectiveness research, health care quality and value, and personalized medicine support these efforts and have resulted in considerable progress to date. An emerging initiative, and one that integrates these converging approaches to improving health care, is “rapid-learning health care.” In this framework, routinely collected real-time clinical data drive the process of scientific discovery, which becomes a natural outgrowth of patient care. To better understand the state of the rapid-learning health care model and its potential implications for oncology, the National Cancer Policy Forum of the Institute of Medicine held a workshop entitled “A Foundation for Evidence-Driven Practice: A Rapid-Learning System for Cancer Care” in October 2009. Participants examined the elements of a rapid-learning system for cancer, including registries and databases, emerging information technology, patient-centered and -driven clinical decision support, patient engagement, culture change, clinical practice guidelines, point-of-care needs in clinical oncology, and federal policy issues and implications. This Special Article reviews the activities of the workshop and sets the stage to move from vision to action. PMID:20585094

The "medication interest model": an integrative clinical interviewing approach for improving medication adherence-part 2: implications for teaching and research.

PubMed

Shea, Shawn Christopher

2009-01-01

Over the past several decades, exciting advances have been made in the art and science of teaching clinical interviewing, which are supported by an ever-growing evidence base documenting their effectiveness. In this second article in a 2-part series, the training and research implications of an innovative approach to improving medication adherence based on these educational advances--the medication interest model (MIM)--are described. The objective is to provide an "insider's view" of how to creatively teach the MIM to case managers, as well as design state-of-the-art courses and research platforms dedicated to improving medication adherence through improved clinical interviewing skills in both nursing and medical student education. The teaching and research design concepts are applicable to all primary care settings as well as specialty areas from endocrinology and cardiology to psychiatry. Evidence-based advances in the teaching of clinical interviewing skills such as response-mode research, facilic supervision, microtraining, and macrotraining lend a distinctive quality and integrative power to the MIM. The model delineates several new platforms for training and research regarding the enhancement of medication adherence including an approach for collecting individual interviewing techniques into manageable "learning modules" amenable to competency evaluation and potential certification.

An updated concept of coagulation with clinical implications.

PubMed

Romney, Gregory; Glick, Michael

2009-05-01

Over the past century, a series of models have been put forth to explain the coagulation mechanism. The coagulation cascade/waterfall model has gained the most widespread acceptance. This model, however, has problems when it is used in different clinical scenarios. A more recently proposed cell-based model better describes the coagulation process in vivo and provides oral health care professionals (OHCPs) with a better understanding of the clinical implications of providing dental care to patients with potentially increased bleeding tendencies. The authors conducted a literature search using the PubMed database. They searched for key words including "coagulation," "hemostasis," "bleeding," "coagulation factors," "models," "prothrombin time," "activated partial thromboplastin time," "international normalized ratio," "anticoagulation therapy" and "hemophilia" separately and in combination. The coagulation cascade/waterfall model is insufficient to explain coagulation in vivo, predict a patient's bleeding tendency, or correlate clinical outcomes with specific laboratory screening tests such as prothrombin time, activated partial thromboplastin time and international normalized ratio. However, the cell-based model of coagulation that reflects the in vivo process of coagulation provides insight into the clinical ramifications of treating dental patients with specific coagulation factor deficiencies. Understanding the in vivo coagulation process will help OHCPs better predict a patient's bleeding tendency. In addition, applying the theoretical concept of the cell-based model of coagulation to commonly used laboratory screening tests for coagulation and bleeding will result in safer and more appropriate dental care.

Deconstructing breast cancer heterogeneity: clinical implications for women with Basal-like tumors.

PubMed

Rattani, Nabila S; Swift-Scanlan, Theresa

2014-11-01

To compare and contrast the molecular and environmental factors contributing to basal-like breast cancer and highlight the clinical implications for women with this phenotype. CINAHL® and PubMed databases, journals, and citation indices were searched using the key word basal-like in combination with breast cancer, epigenetic, treatment, subtype, risk factor, and BRCA1 to synthesize the literature on the multiple underpinnings of basal-like breast cancer. Research findings related to the molecular foundation of basal-like breast cancer were integrated with knowledge of nongenetic contributing risk factors. Approved therapies and those under development were summarized with the goal of improving understanding for research and practice. Of the five subtypes of breast cancer, the basal-like subtype has the shortest survival and poorest prognosis. The development of gene expression assays with epigenetic studies has enabled reliable identification of the basal-like subtype and has shed light on novel therapeutic possibilities. Clinical trials for basal-like breast cancer are underway, and the potential for individualized treatments for women with this subtype show promise. The main difficulties with basal-like breast cancer are its aggressive course, treatment refractory nature, and complex biology, all of which pose real challenges for clinical management and patient education. Oncology nurses play a pivotal role in providing holistic care and patient support. Therefore, nurses must understand the complexity of the clinical presentation and the underlying biology of this cancer subtype.

Communicating microarray results of uncertain clinical significance in consultation summary letters and implications for practice.

PubMed

Paul, Jean Lillian; Pope-Couston, Rachel; Wake, Samantha; Burgess, Trent; Tan, Tiong Yang

2016-01-01

Letter-writing is an integral practice for genetic health professionals. In Victoria, Australia, patients with a chromosomal variant of uncertain clinical significance (VUS) referred to a clinical geneticist (CG) for evaluation receive consultation summary letters. While communication of uncertainty has been explored in research to some extent, little has focused on how uncertainty is communicated within consultation letters. We aimed to develop a multi-layered understanding of the ways in which CGs communicate diagnostic uncertainty in consultation summary letters. We used theme-oriented discourse analysis of 49 consultation summary letters and thematic analysis of a focus group involving eight CGs. Results showed that CGs have become more confident in their description of VUS as 'contributing factors' to patients' clinical features, but remain hesitant to assign definitive causality. CGs displayed strong epistemic stance when discussing future technological improvements to provide hope and minimise potentially disappointing outcomes for patients and families. CGs reported feeling overwhelmed by their workload associated with increasing numbers of patients with VUS, and this has led to a reduction in the number of review appointments offered over time. This study provides a rich description of the content and process of summary letters discussing VUS. Our findings have implications for letter-writing and workforce management. Furthermore, these findings may be of relevance to VUS identified by genomic sequencing in clinical practice.

Implications for would healing of patient age and time elapsed since burn injury.

PubMed

Mountford, E M; Blight, A; Cheshire, I M

1995-01-01

To determine the relationship between growth potential in culture and the age of the patient, skin biopsies were obtained from over 60 patients of varying ages. The relationship between the length of time elapsed since burn injury and growth potential was also examined, using biopsies obtained from patients with burns during their treatment. Keratinocytes were extracted from biopsies and assessed for colony-forming ability by standard methods. Repeated subculture of cells was undertaken to determine the reproductive capacity of cells in vitro. Age had no effect on the colony-forming ability of keratinocytes in primary culture; however age did affect the total number of generations achieved by these cells. The growth potential of keratinocytes from patients with severe burns showed considerable variation according to the amount of time which had elapsed since the injury. This was most apparent around one week post-burn. These results need to be investigated further to understand their clinical implications. The study provides an insight into the influence of age and physiological response on the wound healing process in burn injuries.

Ethical Implications in the Use of Embryonic and Adult Neural Stem Cells

PubMed Central

Ramos-Zúñiga, Rodrigo; González-Pérez, Oscar; Macías-Ornelas, Ana; Capilla-González, Vivian; Quiñones-Hinojosa, Alfredo

2012-01-01

The advent and growth of technological advances have led to new routes of knowledge. Thereby, we currently face new challenges. We have just started to get a glimpse of the structural and functional role of neural stem cells in differentiation and migration processes, the origin of synaptic networks, and subsequent readjustments in specific circuits. A whole range of treatment possibilities originates from this knowledge that potentially can be used for different neurological diseases in humans. Although this is an encouraging scenario, it implies that the human brain is the object of such study, as well as its potential manipulation and transplantation. It is, therefore, pertinent that ethical principles should be followed in such research to have proper balance between what can be done and what should be done, according to every specific context. Hence, it is wise to consider ethical implications in every research project, along with potential clinical applications, under the principle of causing no harm, following risk and benefit rules in decision making and with respect of the human condition as a priority. PMID:22997522

An 'integrative neuroscience' perspective on ADHD: linking cognition, emotion, brain and genetic measures with implications for clinical support.

PubMed

Williams, Leanne M; Tsang, Tracey W; Clarke, Simon; Kohn, Michael

2010-10-01

There remains a translational gap between research findings and their implementation in clinical practice that applies to attention-deficit/hyperactivity disorder (ADHD), as well as to other major disorders of brain health in childhood, adolescence and adulthood. Research studies have identified potential 'markers' to support diagnostic, functional assessment and treatment decisions, but there is little consensus about these markers. Of these potential markers, cognitive measures of thinking functions, such as sustaining attention and associated electrical brain activity, show promise in complementing the clinical management process. Emerging evidence highlights the relevance of emotional, as well as thinking, functions to ADHD. Here, we outline an integrative neuroscience framework for ADHD that offers one means to bring together cognitive measures of thinking functions with measures of emotion, and their brain and genetic correlates. Understanding these measures and the relationships between them is a first step towards the development of tools that will help to assess the heterogeneity of ADHD, and aid in tailoring treatment choices.

[Focus on the Immunoscore and its potential clinical implications].

PubMed

El Sissy, Carine; Marliot, Florence; Haicheur, Nacilla; Kirilovsky, Amos; Scripcariu, Dragos; Lagorce-Pagès, Christine; Galon, Jérôme; Pagès, Franck

2017-02-01

The role of the immune response at the tumor site is now recognized as crucial in the clinical course of patients with cancer. The importance of the immune cell type, their functional orientation, their density and location within the tumor's regions (tumor/invasion margin) has recently been shown and were grouped together under the term "immune contexture". A strong infiltration by cytotoxic and memory T cells in a Th1-polarized tumor microenvironment appears to have a major prognosis impact. A test called Immunoscore taking into account these various parameters has been suggested to measure in a simple, reproducible and robust manner the intra- and peritumoral immune response. The prognostic value of Immunoscore has recently been validated in colon cancers by a large international retrospective study under the aegis of the Society for Immunotherapy of Cancer (SITC). The Immunoscore could have several potential clinical applications such as prognostic as well as theranostic. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Stem cell therapy clinical research: A regulatory conundrum for academia.

PubMed

Nagpal, Anjali; Juttner, Chris; Hamilton-Bruce, Monica Anne; Rolan, Paul; Koblar, Simon A

2017-12-01

The encouraging pace of discovery and development in the field of regenerative medicine holds tremendous potential for bringing therapies to the clinic that may offer meaningful benefit to patients, particularly in diseases with no or suboptimal therapeutic options. Academic researchers will continue to play a critical role in developing concepts and therapies, thus determining whether regenerative medicine will be able to live up to this potential that clearly excites clinicians, researchers and patients alike. This review summarises recent developments in regulatory frameworks across different countries that aim to ensure adequate oversight of the development of regenerative medicine products, which are unique in structural and functional complexity when compared to traditional chemical drugs and fully characterised biological drugs. It discusses the implications of these developments for researchers aiming to make the challenging transition from laboratory to clinical development of these therapies and considers possible pragmatic solutions that could accelerate this process that is essential to maintain research credibility and ensure patient safety. Copyright © 2016 Elsevier B.V. All rights reserved.

Proteomic study of acute respiratory distress syndrome: current knowledge and implications for drug development

PubMed Central

Levitt, Joseph E.; Rogers, Angela J.

2017-01-01

The acute respiratory distress syndrome (ARDS) is a common cause of acute respiratory failure, and is associated with substantial mortality and morbidity. Dozens of clinical trials targeting ARDS have failed, with no drug specifically targeting lung injury in widespread clinical use. Thus, the need for drug development in ARDS is great. Targeted proteomic studies in ARDS have identified many key pathways in the disease, including inflammation, epithelial injury, endothelial injury or activation, and disordered coagulation and repair. Recent studies reveal the potential for proteomic changes to identify novel subphenotypes of ARDS patients who may be most likely to respond to therapy and could thus be targeted for enrollment in clinical trials. Nontargeted studies of proteomics in ARDS are just beginning and have the potential to identify novel drug targets and key pathways in the disease. Proteomics will play an important role in phenotyping of patients and developing novel therapies for ARDS in the future. PMID:27031735

Can the FDA improve oversight of foreign clinical trials?: Closing the information gap and moving towards a globalized regulatory scheme.

PubMed

Ourso, André

2012-01-01

Currently, pharmaceutical companies' utilization of foreign clinical trial data is a ubiquitous and indispensable aspect of gaining approval to market drugs in the United States. Cost benefits, a larger pool of ready volunteer subjects, and greater efficiency in clinical testing are some of the reasons for conducting clinical trials overseas. Despite these advantages, lack of proper oversight may have serious public health implications regarding the integrity of clinical research, ethical treatment of human subjects, and drug safety. Due to the expansive global nature of foreign clinical trials, there are concerns with the FDA's ability to monitor and regulate these trials. This article examines the FDA's oversight of foreign clinical trials and the agency's limitations regulating these trials. In addition to looking at steps the FDA is taking to address these limitations, the article examines other potential regulatory and cooperative actions that can be taken to effectively monitor foreign clinical trials and to ensure data integrity and patient safety.

A review of factors explaining variability in fentanyl pharmacokinetics; focus on implications for cancer patients

PubMed Central

Zandvliet, Maarten L.; Koolen, Stijn L. W.; Mathijssen, Ron H. J.; van der Rijt, Carin C. D.

2016-01-01

Fentanyl is a strong opioid that is available for various administration routes, and which is widely used to treat cancer‐related pain. Many factors influence the fentanyl pharmacokinetics leading to a wide inter‐ and intrapatient variability. This systematic review summarizes multiple studied factors that potentially influence fentanyl pharmacokinetics with a focus on implications for cancer patients. The use of CYP3A4 inhibitors and inducers, impaired liver function, and heating of the patch potentially influence fentanyl pharmacokinetics in a clinically relevant way. In elderly patients, current data suggest that we should carefully dose fentanyl due to alterations in absorption and metabolism. The influence of BMI and gender on fentanyl pharmacokinetics is questionable, most probably due to a large heterogeneity in the published studies. Pharmacogenetics, e.g. the CYP3A5*3 gene polymorphism, may influence fentanyl pharmacokinetics as well, although further study is warranted. Several other factors have been studied but did not show significant and clinically relevant effects on fentanyl pharmacokinetics. Unfortunately, most of the published papers that studied factors influencing fentanyl pharmacokinetics describe healthy volunteers instead of cancer patients. Results from the studies in volunteers may not be simply extrapolated to cancer patients because of multiple confounding factors. To handle fentanyl treatment in a population of cancer patients, it is essential that physicians recognize factors that influence fentanyl pharmacokinetics, thereby preventing potential side‐effects and increasing its efficacy. PMID:27619152

Therapeutic Potential of Matrix Metalloproteinase Inhibition in Breast Cancer

PubMed Central

Raeeszadeh‐Sarmazdeh, Maryam; Radisky, Derek C.

2017-01-01

ABSTRACT Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases that cleave nearly all components of the extracellular matrix as well as many other soluble and cell‐associated proteins. MMPs have been implicated in normal physiological processes, including development, and in the acquisition and progression of the malignant phenotype. Disappointing results from a series of clinical trials testing small molecule, broad spectrum MMP inhibitors as cancer therapeutics led to a re‐evaluation of how MMPs function in the tumor microenvironment, and ongoing research continues to reveal that these proteins play complex roles in cancer development and progression. It is now clear that effective targeting of MMPs for therapeutic benefit will require selective inhibition of specific MMPs. Here, we provide an overview of the MMP family and its biological regulators, the tissue inhibitors of metalloproteinases (TIMPs). We then summarize recent research from model systems that elucidate how specific MMPs drive the malignant phenotype of breast cancer cells, including acquisition of cancer stem cell features and induction of the epithelial–mesenchymal transition, and we also outline clinical studies that implicate specific MMPs in breast cancer outcomes. We conclude by discussing ongoing strategies for development of inhibitors with therapeutic potential that are capable of selectively targeting the MMPs most responsible for tumor promotion, with special consideration of the potential of biologics including antibodies and engineered proteins based on the TIMP scaffold. J. Cell. Biochem. 118: 3531–3548, 2017. © 2017 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc. PMID:28585723

Prepubertal Gynecomastia Due to Indirect Exposure to Nonformulary Bioidentical Hormonal Replacement Therapy: A Case Report.

PubMed

De Pinho, Joao Correia; Aghajanova, Lusine; Herndon, Christopher N

2016-01-01

Gynecomastia is a disorder of the endocrine system characterized by an abnormal presence of a palpable unilateral or bilateral enlargement and proliferation of glandular ductal benign breast tissue in male individuals. This case discusses the medical implications of an unregulated, indirect exposure to nonformulary, bioidentical hormone replacement therapy in male children. An 8-year-old boy presented with prepubertal gynecomastia secondary to estrogen exposure from maternal use of bioidentical hormonal replacement therapy (the Wiley protocol). We review the literature on prepubertal gynecomastia secondary to exogenous estrogen exposure, evaluation, clinical surveillance of the pubertal development, and relevant short- and long-term implications. Indirect exposure to nonformulary hormonal replacement in our case report was an etiologic factor in the development of prepubertal gynecomastia. This novel estrogen exposure source has important implications in the differential diagnosis of prepubertal gynecomastia and potential adverse effects secondary to precocious hormonal exposure.

Epigenetic developmental programs and adipogenesis: implications for psychotropic induced obesity.

PubMed

Chase, Kayla; Sharma, Rajiv P

2013-11-01

Psychotropic agents are notorious for their ability to increase fat mass in psychiatric patients. The two determinants of fat mass are the production of newly differentiated adipocytes (adipogenesis), and the volume of lipid accumulation. Epigenetic programs have a prominent role in cell fate commitments and differentiation required for adipogenesis. In parallel, epigenetic effects on energy metabolism are well supported by several genetic models. Consequently, a variety of psychotropics, often prescribed in combinations and for long periods, may utilize a common epigenetic effector path causing an increase in adipogenesis or reduction in energy metabolism. In particular, the recent discovery that G protein coupled signaling cascades can directly modify epigenetic regulatory enzymes implicates surface receptor activity by psychotropic medications. The potential therapeutic implications are also suggested by the effects of the clinically approved antidepressant tranylcypromine, also a histone demethylase inhibitor, which has impressive therapeutic effects on metabolism in the obese phenotype.

Modelling the resource implications of managing adults with Fabry disease in Norway favours home infusion.

PubMed

Guest, Julian F; Jenssen, Trond; Houge, Gunnar; Aaseboe, Willy; Tøndel, Camilla; Svarstad, Einar

2010-12-01

The aim of this study was to estimate the resource implications and budget impact of managing adults with Fabry disease in Norway, from the perspective of the publicly funded healthcare system. A decision model was constructed using published clinical outcomes and clinician-derived resource utilization estimates. The model was used to estimate the annual healthcare cost of managing a cohort of 64 adult Fabry patients in an average year. The expected annual cost of managing 60 existing Fabry patients and four new patients in Norway each year was estimated to be NOK 55·8 million (€6·7 million). In an average year, patients receiving enzyme replacement therapy (ERT) with agalsidase alfa (Replagal(®)) at 0·2 mg kg⁻¹ or agalsidase beta (Fabrazyme(®)) at 1·0 mg kg⁻¹ are collectively expected to make 586 attendances to their family practitioner's office for their infusions, which equates to 128 eight-hour days associated with ERT. Encouraging more patients to undergo home-based infusions has substantial potential to free-up community-based resources. In comparison, the community-related benefit that can be obtained by switching from agalsidase beta (1·0 mg kg⁻¹) to agalsidase alpha (0·2 mg kg⁻¹) is marginal, and dependent on the two doses being clinically equivalent. Maximizing the proportion of adults with Fabry disease undergoing home-based infusions has the potential to release community-based resources for alternative use by non-Fabry patients, thereby improving the efficiency of the publicly funded healthcare system in Norway. © 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.

Stigma, social anxiety, and illness severity in bipolar disorder: Implications for treatment.

PubMed

Levy, Boaz; Tsoy, Elena; Brodt, Madeline; Petrosyan, Karen; Malloy, Mary

2015-02-01

Studies indicate that comorbid anxiety disorders predict a more severe course of illness in bipolar disorder (BD). The relatively high prevalence of social anxiety in BD points to the potential role that socio-cultural factors, such as stigma, play in exacerbating the progression of this disorder. Stigma creates social anxiety in affected individuals because it essentially forces them into a vulnerable social status that is marked by public disgrace. Although the etiology of debilitating social anxiety in BD may involve multiple factors, stigma deserves particular clinical attention because research in this area indicates that it is common and its internalization is associated with poor outcome. We conducted a literature review using search terms related to stigma, social anxiety, bipolar disorder, illness severity, and outcomes. The electronic databases searched included PsychINFO, PubMed, JSTOR, and EBSCOhost Academic Search Complete with limits set to include articles published in English. The literature indicates that internalized stigma often triggers the core psychological experiences of social anxiety and is highly correlated with clinical and functional outcome in BD. On a psychological level, internalized stigma and social anxiety can create distress that triggers symptoms of BD. From a biological perspective, stigma constitutes a chronic psychosocial stressor that may interact with the pathophysiology of BD in inflammatory ways. The connection between stigma and social anxiety, and their combined effects on people with BD, carries important implications for psychiatric care. To obtain an accurate clinical formulation, initial evaluations may seek to examine stigma-related experiences and determine their relationship to anxiety symptoms and psychosocial functioning. In addition, direct interventions for reducing the ill effects of stigma in BD deserve clinical attention, because they may carry the potential to enhance outcomes.

Prognostic Implications of Multiplex Detection of KRAS Mutations in Cell-Free DNA from Patients with Pancreatic Ductal Adenocarcinoma.

PubMed

Kim, Min Kyeong; Woo, Sang Myung; Park, Boram; Yoon, Kyong-Ah; Kim, Yun-Hee; Joo, Jungnam; Lee, Woo Jin; Han, Sung-Sik; Park, Sang-Jae; Kong, Sun-Young

2018-04-01

Cell-free DNA (cfDNA) is known to provide potential biomarkers for predicting clinical outcome, but its value in pancreatic ductal adenocarcinoma (PDAC) has not been fully evaluated. The aim of this study was to evaluate the clinical applicability of quantitative analysis of multiplex KRAS mutations in cell-free DNA from patients with PDAC. A total of 106 patients with PDAC were enrolled in this prospective study. The concentration and fraction of KRAS mutations were determined through multiplex detection of KRAS mutations in plasma samples by use of a droplet digital PCR kit (Bio-Rad). KRAS mutations were detected in 96.1% of tissue samples. Eighty patients (80.5%) harbored KRAS mutations in cfDNA, with a median KRAS mutation concentration of 0.165 copies/μL and a median fractional abundance of 0.415%. Multivariable analyses demonstrated that the KRAS mutation concentration [hazard ratio (HR), 2.08; 95% CI, 1.20-3.63] and KRAS fraction (HR, 1.73; 95% CI, 1.02-2.95) were significant factors for progression-free survival. KRAS mutation concentration (HR, 1.97; 95% CI, 1.05-3.67) also had prognostic implications for overall survival. Subgroup analyses showed that KRAS mutation concentration and fractional abundance significantly affected progression-free survival in resectable PDAC ( P = 0.016). Moreover, when combined with the cancer biomarker CA19-9, the KRAS mutation concentration in cfDNA showed additive benefits for the prediction of overall survival. This study demonstrates that multiplex detection of KRAS mutations in plasma cfDNA is clinically relevant, providing a potential candidate biomarker for prognosis of PDAC. © 2018 American Association for Clinical Chemistry.

N-3 Polyunsaturated Fatty Acids through the Lifespan: Implication for Psychopathology

PubMed Central

Pusceddu, Matteo M.; Kelly, Philip; Stanton, Catherine; Cryan, John F.

2016-01-01

Objective: The impact of lifetime dietary habits and their role in physical, mental, and social well-being has been the focus of considerable recent research. Omega-3 polyunsaturated fatty acids as a dietary constituent have been under the spotlight for decades. Omega-3 polyunsaturated fatty acids constitute key regulating factors of neurotransmission, neurogenesis, and neuroinflammation and are thereby fundamental for development, functioning, and aging of the CNS. Of note is the fact that these processes are altered in various psychiatric disorders, including attention deficit hyperactivity disorder, depression, and Alzheimer’s disease. Design: Relevant literature was identified through a search of MEDLINE via PubMed using the following words, “n-3 PUFAs,” “EPA,” and “DHA” in combination with “stress,” “cognition,” “ADHD,” “anxiety,” “depression,” “bipolar disorder,” “schizophrenia,” and “Alzheimer.” The principal focus was on the role of omega-3 polyunsaturated fatty acids throughout the lifespan and their implication for psychopathologies. Recommendations for future investigation on the potential clinical value of omega-3 polyunsaturated fatty acids were examined. Results: The inconsistent and inconclusive results from randomized clinical trials limits the usage of omega-3 polyunsaturated fatty acids in clinical practice. However, a body of literature demonstrates an inverse correlation between omega-3 polyunsaturated fatty acid levels and quality of life/ psychiatric diseases. Specifically, older healthy adults showing low habitual intake of omega-3 polyunsaturated fatty acids benefit most from consuming them, showing improved age-related cognitive decline. Conclusions: Although further studies are required, there is an exciting and growing body of research suggesting that omega-3 polyunsaturated fatty acids may have a potential clinical value in the prevention and treatment of psychopathologies. PMID:27608809

Neuronal and molecular effects of cannabidiol on the mesolimbic dopamine system: Implications for novel schizophrenia treatments.

PubMed

Renard, Justine; Norris, Christopher; Rushlow, Walter; Laviolette, Steven R

2017-04-01

Growing clinical and pre-clinical evidence points to a critical role for cannabidiol (CBD), the largest phytochemical component of cannabis, as a potential pharmacotherapy for various neuropsychiatric disorders. In contrast to delta-9-tetrahydrocannabinol (THC), which is associated with acute and neurodevelopmental pro-psychotic side-effects, CBD possesses no known psychoactive or dependence-producing properties. However, evidence has demonstrated that CBD strongly modulates the mesolimbic dopamine (DA) system and may possess promising anti-psychotic properties. Despite the psychotropic differences between CBD and THC, little is known regarding their molecular and neuronal effects on the mesolimbic DA system, nor how these differential effects may relate to their potential pro vs. anti-psychotic properties. This review summarizes clinical and pre-clinical evidence demonstrating CBD's modulatory effects on DA activity states within the mesolimbic pathway, functional interactions with the serotonin 5-HT 1A receptor system, and their downstream molecular signaling effects. Together with clinical evidence showing that CBD may normalize affective and cognitive deficits associated with schizophrenia, CBD may represent a promising treatment for schizophrenia, acting through novel molecular and neuronal mesolimbic substrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Histopathological features of clinical perineural invasion of cutaneous squamous cell carcinoma of the head and neck and the potential implications for treatment.

PubMed

Panizza, Benedict; Warren, Timothy A; Solares, C Arturo; Boyle, Glen M; Lambie, Duncan; Brown, Ian

2014-11-01

Nonmelanoma skin cancer (NMSC) with perineural invasion (PNI) is most commonly seen in cutaneous squamous cell carcinoma of the head and neck (SCCHN). The cranial nerves are a conduit for skin cancer to reach the brainstem. The histopathological features of 51 tissue specimens from 49 patients with cutaneous SCCHN and clinical PNI were assessed with consecutive transverse and longitudinal sections. No skip lesions were identified. Tumor spread was contiguous in all specimens. No tumor spread into the perineural space from surrounding or adjacent tumor was seen. Proximal large cranial nerves showed epineural involvement in 3.9% in areas with large tumor bulk, extensive PNI, and intraneural invasion. Perineural tumor spread in cutaneous SCCHN was contiguous and no skip lesions were evident in nerve specimens assessed in this series. Spread beyond cranial nerve perineurium was uncommon, reflecting its multilayer barrier function at this level. These findings may have treatment implications. © 2013 Wiley Periodicals, Inc.

VMAT2 Inhibitors for Tardive Dyskinesia-Practice Implications.

PubMed

Peckham, Alyssa M; Nicewonder, Jessica A

2018-01-01

Tardive dyskinesia is a potentially irreversible, debilitating, hyperkinetic movement disorder that can result from dopamine receptor antagonists. Prompt recognition and resolution of symptoms are instrumental in preventing disease irreversibility, though current treatment options have fallen short of robust, effective, and long-term symptom control. In April 2017, the Food and Drug Administration (FDA) approved 2 new vesicular monoamine transporter 2 (VMAT2) inhibitors, deutetrabenazine and valbenazine, for chorea related to Huntington's disease and tardive dyskinesia, respectively. These agents were pharmacologically modified from tetrabenazine, a VMAT2 inhibitor used off-label in the treatment of tardive dyskinesia. Despite FDA-labeled indications of deutetrabenazine and valbenazine, each agent was explored as a treatment option for those with tardive dyskinesia. In this study, the pharmacologic modifications of the 2 new VMAT2 inhibitors are described, with detailed explanation as to how these may impact clinical practice. The associated case series, observational studies, and clinical trials exploring their use in the treatment of tardive dyskinesia are reported with expert opinion on practice implication.

Contrasting Medical and Legal Standards of Evidence: A Precision Medicine Case Study.

PubMed

Marchant, Gary E; Scheckel, Kathryn; Campos-Outcalt, Doug

2016-03-01

As the health care system transitions to a precision medicine approach that tailors clinical care to the genetic profile of the individual patient, there is a potential tension between the clinical uptake of new technologies by providers and the legal system's expectation of the standard of care in applying such technologies. We examine this tension by comparing the type of evidence that physicians and courts are likely to rely on in determining a duty to recommend pharmacogenetic testing of patients prescribed the oral anti-coagulant drug warfarin. There is a large body of inconsistent evidence and factors for and against such testing, but physicians and courts are likely to weigh this evidence differently. The potential implications for medical malpractice risk are evaluated and discussed. © 2016 American Society of Law, Medicine & Ethics.

Battery-free, wireless sensors for full-body pressure and temperature mapping

PubMed Central

Han, Seungyong; Kim, Jeonghyun; Won, Sang Min; Ma, Yinji; Kang, Daeshik; Xie, Zhaoqian; Lee, Kyu-Tae; Chung, Ha Uk; Banks, Anthony; Min, Seunghwan; Heo, Seung Yun; Davies, Charles R.; Lee, Jung Woo; Lee, Chi-Hwan; Kim, Bong Hoon; Li, Kan; Zhou, Yadong; Wei, Chen; Feng, Xue; Huang, Yonggang; Rogers, John A.

2018-01-01

Thin, soft, skin-like sensors capable of precise, continuous measurements of physiological health have broad potential relevance to clinical health care. Use of sensors distributed over a wide area for full-body, spatiotemporal mapping of physiological processes would be a considerable advance for this field. We introduce materials, device designs, wireless power delivery and communication strategies, and overall system architectures for skin-like, battery-free sensors of temperature and pressure that can be used across the entire body. Combined experimental and theoretical investigations of the sensor operation and the modes for wireless addressing define the key features of these systems. Studies with human subjects in clinical sleep laboratories and in adjustable hospital beds demonstrate functionality of the sensors, with potential implications for monitoring of circadian cycles and mitigating risks for pressure-induced skin ulcers. PMID:29618561

Unacknowledged Rape: The Influences of Child Sexual Abuse and Personality Traits.

PubMed

Wilson, Laura C; Scarpa, Angela

2015-01-01

Evidence supports that the majority of young women who experience sexual victimization that meets the legal definition of rape do not label their experiences as rape--this has been termed unacknowledged rape. In a sample of 77 young adult women, the odds of unacknowledged rape significantly increased as a function of less severe child sexual abuse histories and greater levels of dysfunctional personality traits. Potential explanations for these findings as well as clinical implications are discussed. Because of the potential psychological and societal consequences of unacknowledged rape, it is vital that researchers continue to examine this phenomenon.

Curcumin and treatment of melanoma: The potential role of microRNAs.

PubMed

Lelli, Diana; Pedone, Claudio; Sahebkar, Amirhosssein

2017-04-01

Melanoma is the most aggressive type of skin cancer and is characterized by poor prognosis in its advanced stages because treatments are poorly effective and burdened with severe adverse effects. MicroRNAs (miRNAs) are small non-coding RNAs that are implicated in several cellular processes; they are categorized as oncogenic and tumor suppressor miRNAs. Several miRNAs are implicated in the pathogenesis and progression of melanoma, such as the tumor suppressor miR-let7b that targets cyclin D and regulates cell cycle. Curcumin is a natural compound derived from Curcuma longa L. (turmeric) with anti-cancer properties, documented also in melanoma, and is well tolerated in humans. Pharmacological activity of curcumin is mediated by modulation of several pathways, such as JAK-2/STAT3, thus inhibiting melanoma cell migration and invasion and enhancing apoptosis of these cells. The low oral bioavailability of curcumin has led to the development of curcumin analogues, such as EF24, with greater anti-tumor efficacy and metabolic stability. Potential anti-cancer activity of curcumin and its analogues is also mediated by modulation of miRNAs such as miR21, that is implicated in cell cycle regulation and apoptosis through down-regulation of PTEN and PDCD4 proteins. Curcumin has a potential role in the treatment of melanoma, though further studies are necessary to explore its clinical efficacy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Multiplexed Molecular Diagnostics for Respiratory, Gastrointestinal, and Central Nervous System Infections.

PubMed

Hanson, Kimberly E; Couturier, Marc Roger

2016-11-15

The development and implementation of highly multiplexed molecular diagnostic tests have allowed clinical microbiology laboratories to more rapidly and sensitively detect a variety of pathogens directly in clinical specimens. Current US Food and Drug Administration-approved multiplex panels target multiple different organisms simultaneously and can identify the most common pathogens implicated in respiratory viral, gastrointestinal, or central nervous system infections. This review summarizes the test characteristics of available assays, highlights the advantages and limitations of multiplex technology for infectious diseases, and discusses potential utilization of these new tests in clinical practice. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

[Sleep disturbances and suicidality: relationships and clinical implications].

PubMed

Norra, C; Richter, N

2013-10-01

Besides several risk factors for suicide, there is a recent increase in clinical and epidemiological studies pointing to a potential relationship between sleep loss or sleep disturbances and suicidality. This work, based on a systematic literature research, gives an overview on the findings of relationships between suicidality (i. e., suicidal thoughts, suicide attempts, suicides) and sleep disturbances, especially insomnia, nightmares, but also hypersomnia and nocturnal panic attacks. There is evidence that sleep disturbances in suicidal insomniacs with comorbid psychiatric disorder are independently predictive for suicidality, too. Shared aspects of pathogenesis of the two entities and therapeutic options are also discussed. Recognition of sleep disturbances is essential for suicide prevention in clinical practice. © Georg Thieme Verlag KG Stuttgart · New York.

The Clinical Nurse Leader--new nursing role with global implications.

PubMed

Baernholdt, M; Cottingham, S

2011-03-01

This paper describes the development of the Clinical Nurse Leader (CNL ©) role and education, the CNL's impact and potential to improve quality globally. The need for clinical nurse leadership to improve the quality of health care systems while controlling costs is recognized in reports internationally. In the USA, a new nursing role, the CNL, was developed in response to such reports. CNLs are master's level nurse graduates (although not necessarily recruited from a nursing background) with the skills and knowledge to create change within complex systems and improve outcomes while they remain direct care providers. This innovative role can be adapted worldwide to improve the quality of health care systems. © 2010 The Authors. International Nursing Review © 2010 International Council of Nurses.

Overview of Experimental and Clinical Findings regarding the Neuroprotective Effects of Cerebral Ischemic Postconditioning.

PubMed

Ma, Di; Feng, Liangshu; Deng, Fang; Feng, Jia-Chun

2017-01-01

Research on attenuating the structural and functional deficits observed following ischemia-reperfusion has become increasingly focused on the therapeutic potential of ischemic postconditioning. In recent years, various methods and animal models of ischemic postconditioning have been utilized. The results of these numerous studies have indicated that the mechanisms underlying the neuroprotective effects of ischemic postconditioning may involve reductions in the generation of free radicals and inhibition of calcium overload, as well as the release of endogenous active substances, alterations in membrane channel function, and activation of protein kinases. Here we review the novel discovery, mechanism, key factors, and clinical application of ischemic postconditioning and discuss its implications for future research and problem of clinical practice.

Enterprise digital assistants: the progression of wireless clinical computing.

PubMed

Bergeron, Bryan P

2002-01-01

By virtue of increasingly pervasive wireless connectivity, the proliferation of wireless handheld devices in clinical care is rapidly transforming the concept of the personal digital assistant (PDA) to the enterprise digital assistant (EDA). Wireless handheld devices are becoming extensions of the central hospital information system, in which it's understood that the health care enterprise, not the clinician carrying the information-dispensing device, owns the data. The practical implication for clinicians is that, despite the potential long-term benefits of seamless, just-in-time clinical data access, this paradigm shift portends decreased efficiency in the short term, as clinicians duplicate clinical data collection on private devices. Assuming eventual clinician acceptance, EDAs can form the basis of a national real-time clinical data acquisition system that ensures uniform prescribing, decision support, and diagnosis, and the means for tracking unusual disease presentation patterns that could be indicative of bioterrorism or natural disease outbreaks.

A Review of Barriers to Minorities' Participation in Cancer Clinical Trials: Implications for Future Cancer Research.

PubMed

Salman, Ali; Nguyen, Claire; Lee, Yi-Hui; Cooksey-James, Tawna

2016-04-01

To enhance nurses' awareness and competencies in practice and research by reporting the common barriers to participation of minorities in cancer clinical trials and discussing facilitators and useful strategies for recruitment. Several databases were searched for articles published in peer reviewed journals. Some of the barriers to minorities' participation in clinical trials were identified within the cultural social-context of cancer patients. The involvement of community networking was suggested as the most effective strategy for the recruitment of minorities in cancer clinical trials. Using culturally sensitive approaches to enhance ethnic minorities' participation is important for advancing cancer care and eliminating health disparities. Awareness of barriers and potential facilitators to the enrollment of ethnic minority cancer patients may contribute to enhancing nurses' competencies of recruiting ethnic minorities in nursing research, playing efficient roles in cancer clinical trials team, and providing culturally competent quality care.

Speech and nonspeech: What are we talking about?

PubMed

Maas, Edwin

2017-08-01

Understanding of the behavioural, cognitive and neural underpinnings of speech production is of interest theoretically, and is important for understanding disorders of speech production and how to assess and treat such disorders in the clinic. This paper addresses two claims about the neuromotor control of speech production: (1) speech is subserved by a distinct, specialised motor control system and (2) speech is holistic and cannot be decomposed into smaller primitives. Both claims have gained traction in recent literature, and are central to a task-dependent model of speech motor control. The purpose of this paper is to stimulate thinking about speech production, its disorders and the clinical implications of these claims. The paper poses several conceptual and empirical challenges for these claims - including the critical importance of defining speech. The emerging conclusion is that a task-dependent model is called into question as its two central claims are founded on ill-defined and inconsistently applied concepts. The paper concludes with discussion of methodological and clinical implications, including the potential utility of diadochokinetic (DDK) tasks in assessment of motor speech disorders and the contraindication of nonspeech oral motor exercises to improve speech function.

Microarray Data Mining for Potential Selenium Targets in Chemoprevention of Prostate Cancer

PubMed Central

ZHANG, HAITAO; DONG, YAN; ZHAO, HONGJUAN; BROOKS, JAMES D.; HAWTHORN, LESLEYANN; NOWAK, NORMA; MARSHALL, JAMES R.; GAO, ALLEN C.; IP, CLEMENT

2008-01-01

Background A previous clinical trial showed that selenium supplementation significantly reduced the incidence of prostate cancer. We report here a bioinformatics approach to gain new insights into selenium molecular targets that might be relevant to prostate cancer chemoprevention. Materials and Methods We first performed data mining analysis to identify genes which are consistently dysregulated in prostate cancer using published datasets from gene expression profiling of clinical prostate specimens. We then devised a method to systematically analyze three selenium microarray datasets from the LNCaP human prostate cancer cells, and to match the analysis to the cohort of genes implicated in prostate carcinogenesis. Moreover, we compared the selenium datasets with two datasets obtained from expression profiling of androgen-stimulated LNCaP cells. Results We found that selenium reverses the expression of genes implicated in prostate carcinogenesis. In addition, we found that selenium could counteract the effect of androgen on the expression of a subset obtained from androgen-regulated genes. Conclusions The above information provides us with a treasure of new clues to investigate the mechanism of selenium chemoprevention of prostate cancer. Furthermore, these selenium target genes could also serve as biomarkers in future clinical trials to gauge the efficacy of selenium intervention. PMID:18548127

The Impact of Genomic Changes on Treatment of Lung Cancer

PubMed Central

Cardarella, Stephanie

2013-01-01

The remarkable success of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors in patients with EGFR mutations and ALK rearrangements, respectively, introduced the era of targeted therapy in advanced non-small cell lung cancer (NSCLC), shifting treatment from platinum-based combination chemotherapy to molecularly tailored therapy. Recent genomic studies in lung adenocarcinoma identified other potential therapeutic targets, including ROS1 rearrangements, RET fusions, MET amplification, and activating mutations in BRAF, HER2, and KRAS in frequencies exceeding 1%. Lung cancers that harbor these genomic changes can potentially be targeted with agents approved for other indications or under clinical development. The need to generate increasing amounts of genomic information should prompt health-care providers to be mindful of the amounts of tissue needed for these assays when planning diagnostic procedures. In this review, we summarize oncogenic drivers in NSCLC that can be currently detected, highlight their potential therapeutic implications, and discuss practical considerations for successful application of tumor genotyping in clinical decision making. PMID:23841470

Unravelling tumour heterogeneity using next-generation imaging: radiomics, radiogenomics, and habitat imaging.

PubMed

Sala, E; Mema, E; Himoto, Y; Veeraraghavan, H; Brenton, J D; Snyder, A; Weigelt, B; Vargas, H A

2017-01-01

Tumour heterogeneity in cancers has been observed at the histological and genetic levels, and increased levels of intra-tumour genetic heterogeneity have been reported to be associated with adverse clinical outcomes. This review provides an overview of radiomics, radiogenomics, and habitat imaging, and examines the use of these newly emergent fields in assessing tumour heterogeneity and its implications. It reviews the potential value of radiomics and radiogenomics in assisting in the diagnosis of cancer disease and determining cancer aggressiveness. This review discusses how radiogenomic analysis can be further used to guide treatment therapy for individual tumours by predicting drug response and potential therapy resistance and examines its role in developing radiomics as biomarkers of oncological outcomes. Lastly, it provides an overview of the obstacles in these emergent fields today including reproducibility, need for validation, imaging analysis standardisation, data sharing and clinical translatability and offers potential solutions to these challenges towards the realisation of precision oncology. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Auditory steady-state evoked potentials vs. compound action potentials for the measurement of suppression tuning curves in the sedated dog puppy.

PubMed

Markessis, Emily; Poncelet, Luc; Colin, Cécile; Hoonhorst, Ingrid; Collet, Grégory; Deltenre, Paul; Moore, Brian C J

2010-06-01

Auditory steady-state evoked potential (ASSEP) tuning curves were compared to compound action potential (CAP) tuning curves, both measured at 2 Hz, using sedated beagle puppies. The effect of two types of masker (narrowband noise and sinusoidal) on the tuning curve parameters was assessed. Whatever the masker type, CAP tuning curve parameters were qualitatively and quantitatively similar to the ASSEP ones, with a similar inter-subject variability, but with a greater incidence of upward tip displacement. Whatever the procedure, sinusoidal maskers produced sharper tuning curves than narrow-band maskers. Although these differences are not likely to have significant implications for clinical work, from a fundamental point of view, their origin requires further investigations. The same amount of time was needed to record a CAP and an ASSEP 13-point tuning curve. The data further validate the ASSEP technique, which has the advantages of having a smaller tendency to produce upward tip shifts than the CAP technique. Moreover, being non invasive, ASSEP tuning curves can be easily repeated over time in the same subject for clinical and research purposes.

Discerning trends in multiplex immunoassay technology with potential for resource-limited settings.

PubMed

Gordon, Julian; Michel, Gerd

2012-04-01

In the search for more powerful tools for diagnoses of endemic diseases in resource-limited settings, we have been analyzing technologies with potential applicability. Increasingly, the process focuses on readily accessible bodily fluids combined with increasingly powerful multiplex capabilities to unambiguously diagnose a condition without resorting to reliance on a sophisticated reference laboratory. Although these technological advances may well have important implications for the sensitive and specific detection of disease, to date their clinical utility has not been demonstrated, especially in resource-limited settings. Furthermore, many emerging technological developments are in fields of physics or engineering, which are not readily available to or intelligible to clinicians or clinical laboratory scientists. This review provides a look at technology trends that could have applicability to high-sensitivity multiplexed immunoassays in resource-limited settings. Various technologies are explained and assessed according to potential for reaching relevant limits of cost, sensitivity, and multiplex capability. Frequently, such work is reported in technical journals not normally read by clinical scientists, and the authors make enthusiastic claims for the potential of their technology while ignoring potential pitfalls. Thus it is important to draw attention to technical hurdles that authors may not be publicizing. Immunochromatographic assays, optical methods including those involving waveguides, electrochemical methods, magnetorestrictive methods, and field-effect transistor methods based on nanotubes, nanowires, and nanoribbons reveal possibilities as next-generation technologies.

Integrative intervention: a new perspective and brief review in aphasia.

PubMed

Marshall, Rebecca Shisler; Mohapatra, Bijoyaa

2017-09-01

While integrative treatment practices have become a popular treatment in different areas of study, its use in the field of aphasiology is still limited. The following paper is an attempt to address the different alternative practices that could potentially be used to remediate aphasia. A narrative review was completed regarding integrative intervention that could potentially apply to aphasia population. Through this article we have explored various treatment options for integrative health care in aphasiology. Integrative treatments including brain specific antioxidants, progesterone and estradiol therapy, nutrition, synbiotic treatment, exercise, yoga, meditation and positive mood states have demonstrated positive changes in health and behavior in healthy aging or disorders such as stroke and aphasia. Offering integrative treatment for people with aphasia allows potential for high impact gains when combined with current speech language therapeutic practices. This paper highlights the rehabilitation possibilities for aphasia therapy. Combining complementary and traditional treatment approaches could be viewed as one of the contemporary approaches to clinical practice and research for practitioners and health care systems. Implications for Rehabilitation There has been very little research that explores the potential of various types of integrative treatment for individuals with aphasia. An integrative approach to the treatment of aphasia has potential for future clinical application. Combining treatment approaches could be viewed as a viable approach to clinical practice and in the health care system.

Principles of three-dimensional printing and clinical applications within the abdomen and pelvis.

PubMed

Bastawrous, Sarah; Wake, Nicole; Levin, Dmitry; Ripley, Beth

2018-04-04

Improvements in technology and reduction in costs have led to widespread interest in three-dimensional (3D) printing. 3D-printed anatomical models contribute to personalized medicine, surgical planning, and education across medical specialties, and these models are rapidly changing the landscape of clinical practice. A physical object that can be held in one's hands allows for significant advantages over standard two-dimensional (2D) or even 3D computer-based virtual models. Radiologists have the potential to play a significant role as consultants and educators across all specialties by providing 3D-printed models that enhance clinical care. This article reviews the basics of 3D printing, including how models are created from imaging data, clinical applications of 3D printing within the abdomen and pelvis, implications for education and training, limitations, and future directions.

Does integrating research into the prosthetics and orthotics undergraduate curriculum enhance students' clinical practice? An interview study on students' perception.

PubMed

Al Qaroot, Bashar S; Sobuh, Mohammad

2016-06-01

Problem-based learning (where rather than feeding students the knowledge, they look for it themselves) has long been thought of as an ideal approach in teaching because it would encourage students to acquire knowledge from an undetermined medium of wrong and right answers. However, the effect of such approach in the learning experience of prosthetics and orthotics students has never been investigated. This study explores the implications of integrating problem-based learning into teaching on the students' learning experience via implementing a research-informed clinical practice module into the curriculum of last year prosthetics and orthotics undergraduate students at the University of Jordan (Amman, Jordan). Qualitative research pilot study. Grounded theory approach was used based on the data collected from interviewing a focus group of four students. Students have identified a number of arguments from their experience in the research-informed clinical practice where, generally speaking, students described research-informed clinical practice as a very good method of education. Integrating problem-based learning into teaching has many positive implications. In particular, students pointed out that their learning experience and clinical practice have much improved after the research-informed clinical practice. Findings from this investigation demonstrate that embedding problem-based learning into prosthetics and orthotics students' curriculum has the potential to enhance students' learning experience, particularly students' evidence-based practice. This may lead to graduates who are more knowledgeable and thus who can offer the optimal patient care (i.e. clinical practice). © The International Society for Prosthetics and Orthotics 2014.

Inhibitors in haemophilia A: a perspective on clotting factor products as a potential contributing factor.

PubMed

Mathew, P; Dinter, H; Church, N; Humphries, T J; Kulkarni, R

2016-05-01

The occurrence of a neutralizing antibody in previously untreated patients (PUPs) with haemophilia A appears to be the result of an intricate interplay of both genetic and environmental factors. Recently, the type of factor VIII (FVIII) product used in the PUPs population has been implicated as a risk factor for inhibitor development. The aim of this review was to explore in a systematic manner potential hypotheses for the product-related findings in these studies (i.e. differences in the expression system of the cell lines used to produce recombinant FVIII [rFVIII], differences in the administered antigen load or changes in clinical practice over time). Review of the available clinical studies illustrates the high degree of variability for the risk of inhibitor development for the same products across different studies. Differences in cell lines or antigen load were not found to provide a reasonable explanation. The possibility of changes in clinical practice over time and patient selection bias (i.e. the preferential use of one product over another in patients at higher risk for inhibitors) offers a potential explanation and should be carefully considered when evaluating the studies. © 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Methodological issues and recommendations for systematic reviews of prognostic studies: an example from cardiovascular disease.

PubMed

Dretzke, Janine; Ensor, Joie; Bayliss, Sue; Hodgkinson, James; Lordkipanidzé, Marie; Riley, Richard D; Fitzmaurice, David; Moore, David

2014-12-03

Prognostic factors are associated with the risk of future health outcomes in individuals with a particular health condition. The prognostic ability of such factors is increasingly being assessed in both primary research and systematic reviews. Systematic review methodology in this area is continuing to evolve, reflected in variable approaches to key methodological aspects. The aim of this article was to (i) explore and compare the methodology of systematic reviews of prognostic factors undertaken for the same clinical question, (ii) to discuss implications for review findings, and (iii) to present recommendations on what might be considered to be 'good practice' approaches. The sample was comprised of eight systematic reviews addressing the same clinical question, namely whether 'aspirin resistance' (a potential prognostic factor) has prognostic utility relative to future vascular events in patients on aspirin therapy for secondary prevention. A detailed comparison of methods around study identification, study selection, quality assessment, approaches to analysis, and reporting of findings was undertaken and the implications discussed. These were summarised into key considerations that may be transferable to future systematic reviews of prognostic factors. Across systematic reviews addressing the same clinical question, there were considerable differences in the numbers of studies identified and overlap between included studies, which could only partially be explained by different study eligibility criteria. Incomplete reporting and differences in terminology within primary studies hampered study identification and selection process across reviews. Quality assessment was highly variable and only one systematic review considered a checklist for studies of prognostic questions. There was inconsistency between reviews in approaches towards analysis, synthesis, addressing heterogeneity and reporting of results. Different methodological approaches may ultimately affect the findings and interpretation of systematic reviews of prognostic research, with implications for clinical decision-making.

Update in Diffuse Parenchymal Lung Disease 2013

PubMed Central

Kaminski, Naftali

2015-01-01

The period covered by this update can be considered as the most exciting period in idiopathic pulmonary fibrosis (IPF) research. It started with the identification of genetic variants that are associated with IPF in the majority of patients and continued with discovery of molecular and genetic biomarkers that predict distinct clinical presentations of patients with IPF and potential new biological mechanisms. More importantly, the period ends with the publication of two groundbreaking studies that confirmed that two drugs, pirfenidone and nintedanib, slowed disease progression, leading to a historic approval by the FDA. In this update, we describe these key advances, their scientific and significant clinical implications, and future directions. PMID:25635490

Psychosocial Correlates of Hepatitis C: Interaction and impact on quality of life

PubMed Central

Janke, E. Amy; McGraw, Sarah; Fraenkel, Liana; Garcia-Tsao, Guadalupe

2009-01-01

Despite demonstrated prevalence of psychosocial problems among hepatitis C (HCV) patients, little is known about how these problems develop, why they are sustained, and how clinical providers can effectively intervene. This study uses a qualitative approach to investigate the nature of psychosocial issues in HCV. Focus groups were conducted with HCV patients during which participants discussed significant feelings of anger, depression, and stigma associated with diagnosis. Participants noted these feelings/experiences isolated them from potential sources of social support. Results have important implications for clinical providers and suggest pathways by which HCV-related psychosocial factors interact and impact of quality of life. PMID:19122126

Seizure clustering.

PubMed

Haut, Sheryl R

2006-02-01

Seizure clusters, also known as repetitive or serial seizures, occur commonly in epilepsy. Clustering implies that the occurrence of one seizure may influence the probability of a subsequent seizure; thus, the investigation of the clustering phenomenon yields insights into both specific mechanisms of seizure clustering and more general concepts of seizure occurrence. Seizure clustering has been defined clinically as a number of seizures per unit time and, statistically, as a deviation from a random distribution, or interseizure interval dependence. This review explores the pathophysiology, epidemiology, and clinical implications of clustering, as well as other periodic patterns of seizure occurrence. Risk factors for experiencing clusters and potential precipitants of clustering are also addressed.

Delayed adverse reactions to the parenteral administration of iodinated contrast media.

PubMed

Egbert, Robert E; De Cecco, Carlo N; Schoepf, U Joseph; McQuiston, Andrew D; Meinel, Felix G; Katzberg, Richard W

2014-12-01

This article presents an overview of delayed adverse reactions (DARs) to parenteral iodinated contrast media and discusses the clinical nature, risk factors, mechanisms, and potential economic implications of these DARs. DARs to contrast media are not rare but are often not recognized as being linked to contrast administration and may be falsely ascribed to other drugs. These side effects are problematic because the patient is usually without medical supervision.

Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury

PubMed Central

Lauritzen, Martin; Dreier, Jens Peter; Fabricius, Martin; Hartings, Jed A; Graf, Rudolf; Strong, Anthony John

2011-01-01

Cortical spreading depression (CSD) and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow (CBF). There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine, stroke, subarachnoid hemorrhage and traumatic brain injury. The implications of these findings are widespread and suggest that intrinsic brain mechanisms have the potential to worsen the outcome of cerebrovascular episodes or brain trauma. The consequences of these intrinsic mechanisms are intimately linked to the composition of the brain extracellular microenvironment and to the level of brain perfusion and in consequence brain energy supply. This paper summarizes the evidence provided by novel invasive techniques, which implicates CSD as a pathophysiological mechanism for this group of acute neurological disorders. The findings have implications for monitoring and treatment of patients with acute brain disorders in the intensive care unit. Drawing on the large body of experimental findings from animal studies of CSD obtained during decades we suggest treatment strategies, which may be used to prevent or attenuate secondary neuronal damage in acutely injured human brain cortex caused by depolarization waves. PMID:21045864

Personalized ophthalmology

PubMed Central

Porter, LF; Black, GCM

2014-01-01

Porter L.F., Black G.C.M. Personalized ophthalmology. Clin Genet 2014: 86: 1–11. © 2014 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd., 2014 Ophthalmology has been an early adopter of personalized medicine. Drawing on genomic advances to improve molecular diagnosis, such as next-generation sequencing, and basic and translational research to develop novel therapies, application of genetic technologies in ophthalmology now heralds development of gene replacement therapies for some inherited monogenic eye diseases. It also promises to alter prediction, diagnosis and management of the complex disease age-related macular degeneration. Personalized ophthalmology is underpinned by an understanding of the molecular basis of eye disease. Two important areas of focus are required for adoption of personalized approaches: disease stratification and individualization. Disease stratification relies on phenotypic and genetic assessment leading to molecular diagnosis; individualization encompasses all aspects of patient management from optimized genetic counseling and conventional therapies to trials of novel DNA-based therapies. This review discusses the clinical implications of these twin strategies. Advantages and implications of genetic testing for patients with inherited eye diseases, choice of molecular diagnostic modality, drivers for adoption of personalized ophthalmology, service planning implications, ethical considerations and future challenges are considered. Indeed, whilst many difficulties remain, personalized ophthalmology truly has the potential to revolutionize the specialty. PMID:24665880

Implication of novel thiazolo-thiophene derivative (MCD-KV-10) for management of asthma.

PubMed

Patil, Dhiraj; Dash, Ranjeet Prasad; Thakur, Sandeep Kumar; Pandya, Amit N; Venkatesh, P; Vasu, Kamala K; Nivsarkar, Manish

2015-04-01

Asthma is multifaceted disease where many targets contribute towards its development and progression. Among these, adenosine receptor subtypes play a major role. MCD-KV-10, a novel thiazolo-thiophene was designed and evaluated pre-clinically for its implication in management of asthma. This compound showed good affinity and selectivity towards A(2A)/A3 adenosine receptor (AR) subtypes. Furthermore, MCD-KV-10 was evaluated for in vitro lipoxygenase inhibition activity; in vivo mast cell stabilization potential and in vivo anti-asthmatic activity was done in ovalbumin-induced airway inflammation model in guinea pigs. The compound showed good (>57%) inhibition of lipoxygenase enzyme and also effectively protected mast cell degranulation (>63%). The compound showed good anti-asthmatic activity as inferred from the in vivo studies. These results indicate that MCD-KV-10 has an inhibitory effect on airway inflammation. Though, we have identified a potential candidate for management of asthma, further mechanistic studies are needed.

Power and knowledge in psychiatry and the troubling case of Dr Osheroff.

PubMed

Robertson, Michael

2005-12-01

To consider the state of knowledge in psychiatry with reference to the 'Osheroff debate' about the treatment of depression. A review of the key philosophical issues regarding the nature of knowledge applied to the Osheroff case. There is an apparent dichotomy between knowledge derived from a reductionist scientific method, as manifest in evidence-based medicine, and that of a narrative form of knowledge derived from clinical experience. The Focauldian notion of knowledge/power and knowledge as discourse suggests that scientific knowledge dominates over narrative knowledge in psychiatry. The implication of this applied to the Osheroff case is the potential annihilation of all forms of knowledge other than science. Knowledge in psychiatry is a pluralist, rather than singularly scientific enterprise. In the Osheroff case, the potential for scientific knowledge to abolish other forms of knowledge posed a serious threat of weakening the profession. In the light of the current debate about best practice, there is a need for reconsideration of the implications of Osheroff.

Natural Antisense Transcripts: Molecular Mechanisms and Implications in Breast Cancers

PubMed Central

Latgé, Guillaume; Poulet, Christophe; Bours, Vincent; Jerusalem, Guy

2018-01-01

Natural antisense transcripts are RNA sequences that can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Because strand-specific high-throughput sequencing of the antisense transcriptome has only been available for less than a decade, many natural antisense transcripts were first described as long non-coding RNAs. Although the precise biological roles of natural antisense transcripts are not known yet, an increasing number of studies report their implication in gene expression regulation. Their expression levels are altered in many physiological and pathological conditions, including breast cancers. Among the potential clinical utilities of the natural antisense transcripts, the non-coding|coding transcript pairs are of high interest for treatment. Indeed, these pairs can be targeted by antisense oligonucleotides to specifically tune the expression of the coding-gene. Here, we describe the current knowledge about natural antisense transcripts, their varying molecular mechanisms as gene expression regulators, and their potential as prognostic or predictive biomarkers in breast cancers. PMID:29301303

Natural Antisense Transcripts: Molecular Mechanisms and Implications in Breast Cancers.

PubMed

Latgé, Guillaume; Poulet, Christophe; Bours, Vincent; Josse, Claire; Jerusalem, Guy

2018-01-02

Natural antisense transcripts are RNA sequences that can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Because strand-specific high-throughput sequencing of the antisense transcriptome has only been available for less than a decade, many natural antisense transcripts were first described as long non-coding RNAs. Although the precise biological roles of natural antisense transcripts are not known yet, an increasing number of studies report their implication in gene expression regulation. Their expression levels are altered in many physiological and pathological conditions, including breast cancers. Among the potential clinical utilities of the natural antisense transcripts, the non-coding|coding transcript pairs are of high interest for treatment. Indeed, these pairs can be targeted by antisense oligonucleotides to specifically tune the expression of the coding-gene. Here, we describe the current knowledge about natural antisense transcripts, their varying molecular mechanisms as gene expression regulators, and their potential as prognostic or predictive biomarkers in breast cancers.

Reactive oxygen species-activated nanomaterials as theranostic agents.

PubMed

Kim, Kye S; Lee, Dongwon; Song, Chul Gyu; Kang, Peter M

2015-01-01

Reactive oxygen species (ROS) are generated from the endogenous oxidative metabolism or from exogenous pro-oxidant exposure. Oxidative stress occurs when there is excessive production of ROS, outweighing the antioxidant defense mechanisms which may lead to disease states. Hydrogen peroxide (H2O2) is one of the most abundant and stable forms of ROS, implicated in inflammation, cellular dysfunction and apoptosis, which ultimately lead to tissue and organ damage. This review is an overview of the role of ROS in different diseases. We will also examine ROS-activated nanomaterials with emphasis on hydrogen peroxide, and their potential medical implications. Further development of the biocompatible, stimuli-activated agent responding to disease causing oxidative stress, may lead to a promising clinical use.

AMPK-mediated regulation of neuronal metabolism and function in brain diseases.

PubMed

Liu, Yu-Ju; Chern, Yijuang

2015-01-01

The AMP-activated protein kinase (AMPK) is a serine/threonine kinase that functions as a key energy sensor in a wide variety of tissues. This kinase has been a major drug target for metabolic diseases (e.g., type 2 diabetes) and cancers. For example, metformin (an activator of AMPK) is a first-line diabetes drug that protects against cancers. Abnormal regulation of AMPK has been implicated in several brain diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke. Given the emerging importance of neurodegenerative diseases in our aging societies, this review features the recent studies that have delineated the functions of AMPK in brain diseases and discusses their potential clinical implications or roles as drug targets in brain diseases.

PDGFRα/β and VEGFR2 polymorphisms in colorectal cancer: incidence and implications in clinical outcome

PubMed Central

2012-01-01

Background Angiogenesis plays an essential role in tumor growth and metastasis, and is a major target in cancer therapy. VEGFR and PDGFR are key players involved in this process. The purpose of this study was to assess the incidence of genetic variants in these receptors and its potential clinical implications in colorectal cancer (CRC). Methods VEGFR2, PDGFRα and PDGFRβ mutations were evaluated by sequencing their tyrosine kinase domains in 8 CRC cell lines and in 92 samples of patients with CRC. Correlations with clinicopathological features and survival were analyzed. Results Four SNPs were identified, three in PDGFRα [exon 12 (A12): c.1701A>G; exon 13 (A13): c.1809G>A; and exon 17 (A17): c.2439+58C>A] and one in PDGFRβ [exon 19 (B19): c.2601A>G]. SNP B19, identified in 58% of tumor samples and in 4 cell lines (LS174T, LS180, SW48, COLO205), was associated with higher PDGFR and pPDGFR protein levels. Consistent with this observation, 5-year survival was greater for patients with PDGFR B19 wild type tumors (AA) than for those harboring the G-allele genotype (GA or GG) (51% vs 17%; p=0.073). Multivariate analysis confirmed SNP B19 (p=0.029) was a significant prognostic factor for survival, independent of age (p=0.060) or TNM stage (p<0.001). Conclusions PDGFRβ exon 19 c.2601A>G SNP is commonly encountered in CRC patients and is associated with increased pathway activation and poorer survival. Implications regarding its potential influence in response to PDGFR-targeted agents remain to be elucidated. PMID:23146028

Legal aspects of clinical ethics committees.

PubMed

Hendrick, J

2001-04-01

In an increasingly litigious society where ritual demands for accountability and "taking responsibility" are now commonplace, it is not surprising that members of clinical ethics committees (CECs) are becoming more aware of their potential legal liability. Yet the vulnerability of committee members to legal action is difficult to assess with any certainty. This is because the CECs which have been set up in the UK are--if the American experience is followed--likely to vary significantly in terms of their functions, procedures, composition, structures and authority. As a consequence it is difficult to generalize about the legal implications. Nevertheless, despite these difficulties this article will outline the broad legal principles governing the potential liability of committee members. It will also consider the relationship between CECs and the courts. It begins, however, with a brief analysis of the relationship between ethics and law in committee deliberations, and in particular of the role of law and legal expertise on CECs.

Use of the electrosurgical unit in a carbon dioxide atmosphere.

PubMed

Culp, William C; Kimbrough, Bradly A; Luna, Sarah; Maguddayao, Aris J; Eidson, Jack L; Paolino, David V

2016-01-01

The electrosurgical unit (ESU) utilizes an electrical discharge to cut and coagulate tissue and is often held above the surgical site, causing a spark to form. The voltage at which the spark is created, termed the breakdown voltage, is governed by the surrounding gaseous environment. Surgeons are now utilizing the ESU laparoscopically with carbon dioxide insufflation, potentially altering ESU operating characteristics. This study examines the clinical implications of altering gas composition by measuring the spark gap distance as a marker of breakdown voltage and use of the ESU on a biologic model, both in room air and carbon dioxide. Paschen's Law predicted a 35% decrease in gap distance in carbon dioxide, while testing revealed an average drop of 37-47% as compared to air. However, surgical model testing revealed no perceivable clinical difference. Electrosurgery can be performed in carbon dioxide environments, although surgeons should be aware of potentially altered ESU performance.

The quality of emergency room radiograph interpretations.

PubMed

McLain, P L; Kirkwood, C R

1985-05-01

Primary care physicians often make patient management decisions based in part on their own interpretations of radiographs. This important area of clinical decision making has not been previously analyzed in the literature. In this series of 294 consecutive radiographs from rural practice, interpretative disagreement between primary care providers and backup radiologists occurred 9.2 percent of the time, a discordance rate similar to that seen among radiologists in other studies. Although a majority of the films for which interpretative disagreement occurred had potential implications for influencing patient management, in only seven cases did actual case management vary from appropriate norms. Follow-up of cases where interpretative disagreement occurred revealed that in only two cases did unsatisfactory outcomes occur. Primary care physicians can provide high-quality radiographic interpretations that, when coupled with clinical information, yield extremely low rates of error or potential for poor patient outcomes.

A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers.

PubMed

Berger, Ashton C; Korkut, Anil; Kanchi, Rupa S; Hegde, Apurva M; Lenoir, Walter; Liu, Wenbin; Liu, Yuexin; Fan, Huihui; Shen, Hui; Ravikumar, Visweswaran; Rao, Arvind; Schultz, Andre; Li, Xubin; Sumazin, Pavel; Williams, Cecilia; Mestdagh, Pieter; Gunaratne, Preethi H; Yau, Christina; Bowlby, Reanne; Robertson, A Gordon; Tiezzi, Daniel G; Wang, Chen; Cherniack, Andrew D; Godwin, Andrew K; Kuderer, Nicole M; Rader, Janet S; Zuna, Rosemary E; Sood, Anil K; Lazar, Alexander J; Ojesina, Akinyemi I; Adebamowo, Clement; Adebamowo, Sally N; Baggerly, Keith A; Chen, Ting-Wen; Chiu, Hua-Sheng; Lefever, Steve; Liu, Liang; MacKenzie, Karen; Orsulic, Sandra; Roszik, Jason; Shelley, Carl Simon; Song, Qianqian; Vellano, Christopher P; Wentzensen, Nicolas; Weinstein, John N; Mills, Gordon B; Levine, Douglas A; Akbani, Rehan

2018-04-09

We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories. Copyright © 2018 Elsevier Inc. All rights reserved.

OTC analgesics and drug interactions: clinical implications

PubMed Central

Fendrick, A Mark; Pan, Deborah E; Johnson, Grace E

2008-01-01

The risk of drug interactions with concurrent use of multiple medications is a clinically relevant issue. Many patients are unaware that over-the-counter (OTC) analgesics can cause potentially serious adverse effects when used in combination with other common medications such as anticoagulants, corticosteroids, or antihypertensive agents. Of particular significance is the increased risk of upper abdominal gastrointestinal adverse events in patients who take traditional nonsteroidal anti-inflammatory drugs (NSAIDs). This risk is dose dependent and further increased in patients who take more than one NSAID or use NSAIDs in combination with certain other medications. Some NSAIDs may also mitigate the antiplatelet benefits of aspirin and may increase blood pressure in patients with hypertension. Clinicians should be aware of potential drug interactions with OTC analgesics when prescribing new medications. Additionally, patients should be properly counseled on the appropriate and safe use of OTC analgesics. PMID:18257920

Clinical implications of basic science discoveries: induced pluripotent stem cell therapy in transplantation--a potential role for immunologic tolerance.

PubMed

Wertheim, J A; Leventhal, J R

2015-04-01

Induced pluripotent stem cells (iPSCs) hold the potential for future development of genetically identical tissues from almost any mature cell lineage. For clinical applications in cell therapy and transplantation, it may provide a means to one-day restore dysfunctional or damaged tissue without the need for immunosuppression. A recent study by de Almeida et al published in the journal Nature Communications indicates that iPSCs may indeed elicit an immune response that evolves as cells differentiate toward maturity to induce a state of tolerance within a recipient animal. If these early findings hold true, it suggests a possible explanation for self-recognition of mature cells derived from iPSCs for use in future therapeutic interventions in transplantation such as cellular therapy or tissue engineering. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Differential diagnosis of Mendelian and mitochondrial disorders in patients with suspected multiple sclerosis

PubMed Central

Katz Sand, Ilana B.; Honce, Justin M.; Lublin, Fred D.

2015-01-01

Several single gene disorders share clinical and radiologic characteristics with multiple sclerosis and have the potential to be overlooked in the differential diagnostic evaluation of both adult and paediatric patients with multiple sclerosis. This group includes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders, and several other miscellaneous disorders. Recognition of a single-gene disorder as causal for a patient’s ‘multiple sclerosis-like’ phenotype is critically important for accurate direction of patient management, and evokes broader genetic counselling implications for affected families. Here we review single gene disorders that have the potential to mimic multiple sclerosis, provide an overview of clinical and investigational characteristics of each disorder, and present guidelines for when clinicians should suspect an underlying heritable disorder that requires diagnostic confirmation in a patient with a definite or probable diagnosis of multiple sclerosis. PMID:25636970

Physiological adaptations following Roux-en-Y gastric bypass and the identification of targets for bariatric mimetic pharmacotherapy.

PubMed

Docherty, Neil G; Le Roux, Carel W

2015-12-01

The present opinion article provides an overview of the key improvements in metabolic and cardiovascular health following Roux-en-Y Gastric Bypass (RYGB). Some clinically important long-term complications of RYGB are also briefly described to contextualise the potential value of finding selective non-surgical means of replicating only the beneficial aspects of RYGB. Three biological responses linked to changes in gastrointestinal tract structure and function post-RYGB, that are implicated in the clinical efficacy of RYGB and that have actual or potential applications as non-surgical mimetic based approaches are addressed. These are (1) exaggerated post-prandial gut hormone responses; (2) local increases in undiluted bile in the gut lumen and augmented circulating bile acid and FGF19 concentrations and (3) compositional changes in the gut microbiota. Copyright © 2015 Elsevier Ltd. All rights reserved.

Obstetric "conveniences": elective induction of labor, cesarean birth on demand, and other potentially unnecessary interventions.

PubMed

Simpson, Kathleen Rice; Thorman, Kathleen E

2005-01-01

Common obstetric interventions are often for "convenience" rather than for clinical indications. Before proceeding, it should be clear who is the beneficiary of the convenience. The primary healthcare provider must make sure that women and their partners have a full understanding of what is known about the associated risks, benefits, and alternative approaches of the proposed intervention. Thorough and accurate information allows women to choose what is best for them and their infant on the basis of the individual clinical situation. Ideally, this discussion takes place during the prenatal period when there is ample opportunity to ask questions, reflect on the potential implications, and confer with partners and family members. A review of common obstetric interventions is provided. While these interventions often are medically indicated for the well-being of mothers and infants, the evidence supporting their benefits when used electively is controversial.

Sacroiliac Pain: A Clinical Approach for the Neurosurgeon

PubMed Central

Moscote-Salazar, Luis Rafael; Alvis-Miranda, Hernando Raphael; Joaquim, Andrei Fernandes; Amaya-Quintero, Jessica; Padilla-Zambrano, Huber S.; Agrawal, Amit

2017-01-01

Pain originating from sacroiliac joint may also cause pain in the lumbar and gluteal region in 15% of the population. The clinical manifestation represents a public health problem due to the great implications on the quality of life and health-related costs. However, this is a diagnosis that is usually ignored in the general clinical practice; probably because of the unknown etiology, making harder to rule out the potential etiologies of this pathology, or maybe because the clinical criteria that support this pathology are unknown. By describing several diagnostic techniques, many authors have studied the prevalence of this pathology, finding more positive data than expected; coming to the conclusion that even though there is no diagnostic gold standard yet, an important amount of cases might be detected by properly applying several tests at the physical examination. Thus, it is necessary to have knowledge of the physiopathology and clinical presentation so that diagnosis can be made to those patients that manifest this problem. We present a clinical approach for the neurosurgeon. PMID:29204025

Cognitive continuum theory in interprofessional healthcare: A critical analysis.

PubMed

Parker-Tomlin, Michelle; Boschen, Mark; Morrissey, Shirley; Glendon, Ian

2017-07-01

Effective clinical decision making is among the most important skills required by healthcare practitioners. Making sound decisions while working collaboratively in interprofessional healthcare teams is essential for modern healthcare planning, successful interventions, and patient care. The cognitive continuum theory (CCT) is a model of human judgement and decision making aimed at orienting decision-making processes. CCT has the potential to improve both individual health practitioner, and interprofessional team understanding about, and communication of, clinical decision-making processes. Examination of the current application of CCT indicates that this theory could strengthen interprofessional team clinical decision making (CDM). However, further research is needed before extending the use of this theoretical framework to a wider range of interprofessional healthcare team processes. Implications for research, education, practice, and policy are addressed.

Instructional Storytelling: Application of the Clinical Judgment Model in Nursing.

PubMed

Timbrell, Jessica

2017-05-01

Little is known about the teaching and learning implications of instructional storytelling (IST) in nursing education or its potential connection to nursing theory. The literature establishes storytelling as a powerful teaching-learning method in the educational, business, humanities, and health sectors, but little exploration exists that is specific to nursing. An example of a story demonstrating application of the domains of Tanner's clinical judgment model links storytelling with learning outcomes appropriate for the novice nursing student. Application of Tanner's clinical judgment model offers consistency of learning experience while preserving the creativity inherent in IST. Further research into student learning outcomes achievement using IST is warranted as a step toward establishing best practices with IST in nursing education. [J Nurs Educ. 2017;56(5):305-308.]. Copyright 2017, SLACK Incorporated.

The need for complex ideas in anorexia nervosa: why biology, environment, and psyche all matter, why therapists make mistakes, and why clinical benchmarks are needed for managing weight correction.

PubMed

Strober, Michael; Johnson, Craig

2012-03-01

Anorexia nervosa remains an enigma and its clinical challenge is intimidating. But the potential for new insights has been advancing, largely as a result of elegant research in the neurosciences that has modeled behavioral processes resembling key features of the illness. Unfortunately, many in the eating disorder field seem to know little of this work or the implication it holds for treatment philosophy. Instead, the knowledge void has been taken up recently by a host of misguided notions about etiology, blatantly dismissive attitudes toward psychological concepts, and ill-conceived beliefs about therapy priorities. This article is a clinical perspective on these issues. Copyright © 2012 Wiley Periodicals, Inc.

Neurophysiology of pain and hypnosis for chronic pain.

PubMed

Dillworth, Tiara; Mendoza, M Elena; Jensen, Mark P

2012-03-01

In the past decade there has been a dramatic increase in (1) understanding the neurophysiological components of the pain experiences, (2) randomized clinical trials testing the efficacy of hypnotic treatments on chronic pain, and (3) laboratory research examining the effects of hypnosis on the neurophysiological processes implicated in pain. Work done in these areas has not only demonstrated the efficacy of hypnosis for treating chronic pain but is beginning to shed light on neurophysiological processes that may play a role in its effectiveness. This paper reviews a selection of published studies from these areas of research, focusing on recent findings that have the most potential to inform both clinical work and research in this area. The paper concludes with research and clinical recommendations for maximizing treatment efficacy based on the research findings that are available.

EG-09EPIGENETIC PROFILING REVEALS A CpG HYPERMETHYLATION PHENOTYPE (CIMP) ASSOCIATED WITH WORSE PROGRESSION-FREE SURVIVAL IN MENINGIOMA

PubMed Central

Olar, Adriana; Wani, Khalida; Mansouri, Alireza; Zadeh, Gelareh; Wilson, Charmaine; DeMonte, Franco; Fuller, Gregory; Jones, David; Pfister, Stefan; von Deimling, Andreas; Sulman, Erik; Aldape, Kenneth

2014-01-01

BACKGROUND: Methylation profiling of solid tumors has revealed biologic subtypes, often with clinical implications. Methylation profiles of meningioma and their clinical implications are not well understood. METHODS: Ninety-two meningioma samples (n = 44 test set and n = 48 validation set) were profiled using the Illumina HumanMethylation450 BeadChip. Unsupervised clustering and analyses for recurrence-free survival (RFS) were performed. RESULTS: Unsupervised clustering of the test set using approximately 900 highly variable markers identified two clearly defined methylation subgroups. One of the groups (n = 19) showed global hypermethylation of a set of markers, analogous to CpG island methylator phenotype (CIMP). These findings were reproducible in the validation set, with 18/48 samples showing the CIMP-positive phenotype. Importantly, of 347 highly variable markers common to both the test and validation set analyses, 107 defined CIMP in the test set and 94 defined CIMP in the validation set, with an overlap of 83 markers between the two datasets. This number is much greater than expected by chance indicating reproducibly of the hypermethylated markers that define CIMP in meningioma. With respect to clinical correlation, the 37 CIMP-positive cases displayed significantly shorter RFS compared to the 55 non-CIMP cases (hazard ratio 2.9, p = 0.013). In an effort to develop a preliminary outcome predictor, a 155-marker subset correlated with RFS was identified in the test dataset. When interrogated in the validation dataset, this 155-marker subset showed a statistical trend (p < 0.1) towards distinguishing survival groups. CONCLUSIONS: This study defines the existence of a CIMP phenotype in meningioma, which involves a substantial proportion (37/92, 40%) of samples with clinical implications. Ongoing work will expand this cohort and examine identification of additional biologic differences (mutational and DNA copy number analysis) to further characterize the aberrant methylation subtype in meningioma. CIMP-positivity with aberrant methylation in recurrent/malignant meningioma suggests a potential therapeutic target for clinically aggressive cases.

2017 update on the relationship between diabetes and colorectal cancer: epidemiology, potential molecular mechanisms and therapeutic implications

PubMed Central

Ardura, Juan Antonio; Corton, Marta; Fernández-Fernández, Beatriz; Aguilera, Oscar; Gomez-Guerrero, Carmen; Mas, Sebastián; Moreno, Juan Antonio; Ruiz-Ortega, Marta; Sanz, Ana Belen; Sanchez-Niño, Maria Dolores; Rojo, Federico; Vivanco, Fernando; Esbrit, Pedro; Ayuso, Carmen; Alvarez-Llamas, Gloria; Egido, Jesús; García-Foncillas, Jesús; Ortiz, Alberto

2017-01-01

Worldwide deaths from diabetes mellitus (DM) and colorectal cancer increased by 90% and 57%, respectively, over the past 20 years. The risk of colorectal cancer was estimated to be 27% higher in patients with type 2 DM than in non-diabetic controls. However, there are potential confounders, information from lower income countries is scarce, across the globe there is no correlation between DM prevalence and colorectal cancer incidence and the association has evolved over time, suggesting the impact of additional environmental factors. The clinical relevance of these associations depends on understanding the mechanism involved. Although evidence is limited, insulin use has been associated with increased and metformin with decreased incidence of colorectal cancer. In addition, colorectal cancer shares some cellular and molecular pathways with diabetes target organ damage, exemplified by diabetic kidney disease. These include epithelial cell injury, activation of inflammation and Wnt/β-catenin pathways and iron homeostasis defects, among others. Indeed, some drugs have undergone clinical trials for both cancer and diabetic kidney disease. Genome-wide association studies have identified diabetes-associated genes (e.g. TCF7L2) that may also contribute to colorectal cancer. We review the epidemiological evidence, potential pathophysiological mechanisms and therapeutic implications of the association between DM and colorectal cancer. Further studies should clarify the worldwide association between DM and colorectal cancer, strengthen the biological plausibility of a cause-and-effect relationship through characterization of the molecular pathways involved, search for specific molecular signatures of colorectal cancer under diabetic conditions, and eventually explore DM-specific strategies to prevent or treat colorectal cancer. PMID:28060743

Ancient wheat species and human health: Biochemical and clinical implications.

PubMed

Dinu, Monica; Whittaker, Anne; Pagliai, Giuditta; Benedettelli, Stefano; Sofi, Francesco

2018-02-01

Wheat is the major staple food in many diets. Based on the increase in worldwide mortality attributable to diet-related chronic diseases, there is an increasing interest in identifying wheat species with greater health potential, more specifically for improved anti-oxidant and anti-inflammatory properties. In particular, ancient varieties (defined as those species that have remained unchanged over the last hundred years) are gaining interest since several studies suggested that they present a healthier nutritional profile than modern wheats. This manuscript reviews the nutritional value and health benefits of ancient wheats varieties, providing a summary of all in vitro, ex vivo, animal and human studies that have thus far been published. Differences in chemical composition, and biochemical and clinical implications of emmer, einkorn, spelt, khorasan and various regional Italian varieties are discussed. Although many studies based on in vitro analyses of grain components provide support to the premise of a healthier nutritional and functional potential of ancient wheat, other in vitro studies performed are not in support of an improved potential of ancient varieties. In the light of existing evidence derived from in vivo experiments, the ancient wheat varieties have shown convincing beneficial effects on various parameters linked to cardio-metabolic diseases such as lipid and glycaemic profiles, as well as the inflammatory and oxidative status. However, given the limited number of human trials, it is not possible to definitively conclude that ancient wheat varieties are superior to all modern counterparts in reducing chronic disease risk. Copyright © 2017 Elsevier Inc. All rights reserved.

Obstructive Sleep Apnea in Children: Implications for the Developing Central Nervous System

PubMed Central

Gozal, David

2008-01-01

Recent increases in our awareness to the high prevalence of sleep disorders in general, and of sleep-disordered breathing among children, in particular, has led to concentrated efforts aiming to understand the pathophysiological mechanisms, clinical manifestations and potential consequences of such conditions. In this review, I will briefly elaborate on some of the pathogenetic elements leading to the occurrence of obstructive sleep apnea (OSA) in children, focus on the psycho-behavioral consequences of pediatric OSA, and review the evidence on the potential mechanisms underlying the close association between CNS morbidity and the episodic hypoxia and sleep fragmentation that characterize OSA. PMID:18555196

Using the 12-Lead Electrocardiogram in the Care of Athletic Patients.

PubMed

Yeo, Tee Joo; Sharma, Sanjay

2016-11-01

This article summarizes the role of the 12-lead electrocardiogram (ECG) for the clinical care of athletes, with particular reference to the influence of age, gender, ethnicity, and type of sport on the appearance of the ECG, and its role in differentiating physiologic exercise-related changes from pathologic conditions implicated in sudden cardiac death (SCD). The article also explores the potential role of the ECG in detecting athletes at risk of SCD. In addition, the article reviews the evolution of ECG interpretation criteria and emphasizes the limitations of the ECG as well as the potential for future research. Copyright © 2016 Elsevier Inc. All rights reserved.

Buying and selling human eggs: infertility providers' ethical and other concerns regarding egg donor agencies.

PubMed

Klitzman, Robert

2016-11-08

Egg donor agencies are increasingly being used as part of IVF in the US, but are essentially unregulated, posing critical ethical and policy questions concerning how providers view and use them, and what the implications might be. Thirty-seven in-depth interviews of approximately 1 h were conducted - with 27 IVF providers and 10 patients. Clinicians vary in their views and interactions concerning egg donor agencies, ranging widely in whether and how often they use agencies. Agencies may offer egg recipients increased choices, but raise ethical and other concerns regarding respect for donors as individuals (e.g., adequacy of informed consent), potential harms, justice (e.g., concerns about possible eugenics - by encouraging and facilitating selection and marketing of facts for offspring), and donors constituting a vulnerable group. The quality of agencies appears to vary considerably, from acceptable to problematic. Agencies' medical and psychological screenings of donors can range, and be minimal. Not all agencies adequately track donors' prior numbers of donations, or share the relevant records with clinics. Clinics may find that potential donors have genetic mutations and medical problems about which they were unaware. Yet agencies and clinics do not provide care for such donors, generating stress. Dissemination of donors' personal data can potentially threaten confidentiality. Questions emerge of whether increased monitoring/oversight of agencies may be beneficial. These data, the first to examine providers' views and interactions regarding egg donor agencies, suggest wide variations in quality and use of agencies, and have critical implications for practice, policy, education and research. Given the potential limitations of the current model of self-regulation of agencies, the present data suggest needs to consider stronger professional guidelines or possible governmental regulations to establish, require and enforce higher standards for agencies to follow, regarding advertising to potential donors and recipients, arranging for appropriate informed consent concerning risks and benefits involved, and for quality control. Appropriate informed consent should be obtained from potential egg donors, including the fact that they may learn about mutations or medical problems about which they were unaware, but for which they will not receive treatment as part of this process. Enhancing understanding among the public-at-large about what egg donation entails may also be helpful.

Opportunities at the Intersection of Bioinformatics and Health Informatics

PubMed Central

Miller, Perry L.

2000-01-01

This paper provides a “viewpoint discussion” based on a presentation made to the 2000 Symposium of the American College of Medical Informatics. It discusses potential opportunities for researchers in health informatics to become involved in the rapidly growing field of bioinformatics, using the activities of the Yale Center for Medical Informatics as a case study. One set of opportunities occurs where bioinformatics research itself intersects with the clinical world. Examples include the correlations between individual genetic variation with clinical risk factors, disease presentation, and differential response to treatment; and the implications of including genetic test results in the patient record, which raises clinical decision support issues as well as legal and ethical issues. A second set of opportunities occurs where bioinformatics research can benefit from the technologic expertise and approaches that informaticians have used extensively in the clinical arena. Examples include database organization and knowledge representation, data mining, and modeling and simulation. Microarray technology is discussed as a specific potential area for collaboration. Related questions concern how best to establish collaborations with bioscientists so that the interests and needs of both sets of researchers can be met in a synergistic fashion, and the most appropriate home for bioinformatics in an academic medical center. PMID:10984461

Fermentation products in the cystic fibrosis airways induce aggregation and dormancy-associated expression profiles in a CF clinical isolate of Pseudomonas aeruginosa.

PubMed

Phan, Joann; Gallagher, Tara; Oliver, Andrew; England, Whitney E; Whiteson, Katrine

2018-05-01

Pseudomonas aeruginosa is a well-known dominant opportunistic pathogen in cystic fibrosis (CF) with a wide range of metabolic capacities. However, P. aeruginosa does not colonize the airways alone, and benefits from the metabolic products of neighboring cells-especially volatile molecules that can travel between different parts of the airways easily. Here, we present a study that investigates the metabolic, gene expression profiles and phenotypic responses of a P. aeruginosa clinical isolate to fermentation products lactic acid and 2,3-butanediol, metabolites that are produced by facultative anaerobic members of the CF polymicrobial community and potential biomarkers of disease progression. Although previous studies have successfully investigated the metabolic and transcriptional profiles of P. aeruginosa, most have used common lab reference strains that may differ in important ways from clinical isolates. Using transcriptomics and metabolomics with gas chromatography time of flight mass spectrometry, we observe that fermentation products induce pyocyanin production along with the expression of genes involved in P. aeruginosa amino acid utilization, dormancy and aggregative or biofilm modes of growth. These findings have important implications for how interactions within the diverse CF microbial community influence microbial physiology, with potential clinical consequences.

Neuregulin in Cardiovascular Development and Disease

PubMed Central

Odiete, Oghenerukevwe; Hill, Michael F.; Sawyer, Douglas B.

2013-01-01

Studies in genetically modified mice have demonstrated that neuregulin-1 (NRG-1), along with the erythroblastic leukemia viral oncogene homolog (ErbB) 2, 3, and 4 receptor tyrosine kinases, is necessary for multiple aspects of cardiovascular development. These observations stimulated in vitro and in vivo animal studies, implicating NRG-1/ErbB signaling in the regulation of cardiac cell biology throughout life. Cardiovascular effects of ErbB2-targeted cancer therapies provide evidence in humans that ErbB signaling plays a role in the maintenance of cardiac function. These and other studies suggest a conceptual model in which a key function of NRG-1/ErbB signaling is to mediate adaptations of the heart to physiological and pathological stimuli through activation of intracellular kinase cascades that regulate tissue plasticity. Recent work implicates NRG-1/ErbB signaling in the regulation of multiple aspects of cardiovascular biology, including angiogenesis, blood pressure, and skeletal muscle responses to exercise. The therapeutic potential of recombinant NRG-1 as a potential treatment for heart failure has been demonstrated in animal models and is now being explored in clinical studies. NRG-1 is found in human serum and plasma, and it correlates with some clinical parameters, suggesting that it may have value as an indicator of prognosis. In this review, we bring together this growing literature on NRG-1 and its significance in cardiovascular development and disease. PMID:23104879

African American Participation in Oncology Clinical Trials--Focus on Prostate Cancer: Implications, Barriers, and Potential Solutions.

PubMed

Ahaghotu, Chiledum; Tyler, Robert; Sartor, Oliver

2016-04-01

In the United States, the incidence and mortality rates of many cancers, especially prostate cancer, are disproportionately high among African American men compared with Caucasian men. Recently, mortality rates for prostate cancer have declined more rapidly in African American versus Caucasian men, but prostate cancer is still the most common cancer and the second leading cause of cancer deaths in African American men in the United States. Compared with Caucasian men, prostate cancer occurs at younger ages, has a higher stage at diagnosis, and is more likely to progress after definitive treatments in African American men. Reasons for racial discrepancies in cancer are multifactorial and potentially include socioeconomic, cultural, nutritional, and biologic elements. In addition to improving access to novel therapies, clinical trial participation is essential to adequately establish the risks and benefits of treatments in African American populations. Considering the disproportionately high mortality rates noted in these groups, our understanding of the natural history and responses to therapies is limited. This review will explore African American underrepresentation in clinical trials with a focus on prostate cancer, and potentially effective strategies to engage African American communities in prostate cancer research. Solutions targeting physicians, investigators, the community, and health care systems are identified. Improvement of African American participation in prostate cancer clinical trials will benefit all stakeholders. Published by Elsevier Inc.

"Milk makes me sick but my body needs it": conflict and contradiction in the establishment of authoritative knowledge.

PubMed

Kingfisher, C P; Millard, A V

1998-12-01

This article takes lactose intolerance as a topic for exploring clashes of power, authority, and knowledge in clinical interactions and interpretations of laywomen. In clinics providing maternal and child care, staff and clients jointly produced authoritative knowledge, most often a version of biomedicine. The Euroamerican staff tended to give advice that was biologically appropriate for them but not for many of their patients, a process reflecting what we refer to as biocentrism. Resulting information given to pregnant and lactating women and diagnoses of children's growth patterns were inappropriate in some cases, with potentially serious legal and health implications. Clinic staff often unwittingly ignored the efforts of their clients to begin a discussion of discrepancies between their bodily knowledge and clinic advice. Some women created their own syntheses, which supported the ascendancy of biomedical knowledge but were not in the interests of their own health.

High fidelity simulation effectiveness in nursing students' transfer of learning.

PubMed

Kirkman, Tera R

2013-07-13

Members of nursing faculty are utilizing interactive teaching tools to improve nursing student's clinical judgment; one method that has been found to be potentially effective is high fidelity simulation (HFS). The purpose of this time series design study was to determine whether undergraduate nursing students were able to transfer knowledge and skills learned from classroom lecture and a HFS clinical to the traditional clinical setting. Students (n=42) were observed and rated on their ability to perform a respiratory assessment. The observations and ratings took place at the bedside, prior to a respiratory lecture, following the respiratory lecture, and following simulation clinical. The findings indicated that there was a significant difference (p=0.000) in transfer of learning demonstrated over time. Transfer of learning was demonstrated and the use of HFS was found to be an effective learning and teaching method. Implications of results are discussed.

Male Contraception: Research, New Methods, and Implications for Marginalized Populations.

PubMed

Plana, Olivia

2017-07-01

The majority of research on contraception has focused on manipulating the female reproductive system. Recent studies have identified novel contraceptives for males, including hormonal- and nonhormonal-based therapeutics. Although these new contraceptives are still undergoing clinical trials, their development and potential future use in society necessitate serious consideration of their implications for reproductive health. Through my analysis of the research conducted on male contraception over time and the current therapeutics available, it is clear that male contraception has the potential to shift societal gender dynamics and provide males with greater control over their own reproduction. This article also identifies the implications of these novel contraceptives for marginalized populations, especially men of color and men of lower socioeconomic positions. To overcome barriers to contraception among these populations, public policy efforts are needed in order to motivate the development of programs that facilitate coverage of these new male contraceptives by health plans and to increase their availability to underserved communities. Health care providers will be responsible for educating patients about these novel male contraception options and the need to continue using existing methods (e.g., condoms) in order to prevent sexually transmitted infections. This article analyzes the research conducted on male contraception and identifies the implications of these novel therapeutics for marginalized groups of men in the United States to identify the interventions that will be necessary to help ensure that all men have access to these promising scientific innovations.

Male Contraception: Research, New Methods, and Implications for Marginalized Populations

PubMed Central

Plana, Olivia

2015-01-01

The majority of research on contraception has focused on manipulating the female reproductive system. Recent studies have identified novel contraceptives for males, including hormonal- and nonhormonal-based therapeutics. Although these new contraceptives are still undergoing clinical trials, their development and potential future use in society necessitate serious consideration of their implications for reproductive health. Through my analysis of the research conducted on male contraception over time and the current therapeutics available, it is clear that male contraception has the potential to shift societal gender dynamics and provide males with greater control over their own reproduction. This article also identifies the implications of these novel contraceptives for marginalized populations, especially men of color and men of lower socioeconomic positions. To overcome barriers to contraception among these populations, public policy efforts are needed in order to motivate the development of programs that facilitate coverage of these new male contraceptives by health plans and to increase their availability to underserved communities. Health care providers will be responsible for educating patients about these novel male contraception options and the need to continue using existing methods (e.g., condoms) in order to prevent sexually transmitted infections. This article analyzes the research conducted on male contraception and identifies the implications of these novel therapeutics for marginalized groups of men in the United States to identify the interventions that will be necessary to help ensure that all men have access to these promising scientific innovations. PMID:26206159

Comparison of student learning in the out-patient clinic and ward round.

PubMed

Davis, M H; Dent, J A

1994-05-01

In undergraduate medical education there is a trend away from ward-based teaching towards out-patient and community-based teaching. To study the potential effects of this altered emphasis on student learning, a pilot group of final-year medical students at the University of Dundee was asked to keep individual structured log-books. These contained details of patients seen during their 3-week orthopaedic attachment in both a ward and out-patient setting. A comparison of perceived learning in the two settings showed that students learned more from attending an out-patient clinic than a ward round, but did not make full use of the learning potential of either. The setting did not particularly influence the balance of learning as categorized here but only the ward round supplied experience of surgical complications. The amount of learning taking place in an out-patient clinic was influenced by student ability, measured by examination performance, but not by clinic work-load. The implications of increased use of out-patient clinics and the advantages and disadvantages of the approach employed are discussed. It is concluded that in the situation studied student learning in the outpatient setting is as good as or superior to the ward setting but should not totally replace it.

A comparative analysis of acute-phase proteins as inflammatory biomarkers in preclinical toxicology studies: implications for preclinical to clinical translation.

PubMed

Watterson, Claire; Lanevschi, Anne; Horner, Judith; Louden, Calvert

2009-01-01

Recently, in early clinical development, a few biologics and small molecules intended as antitumor or anti-inflammatory agents have caused a severe adverse pro-inflammatory systemic reaction also known as systemic inflammatory response syndrome (SIRS). This toxicity could result from expected pharmacological effects of a therapeutic antibody and/or from interaction with antigens expressed on cells/tissues other than the intended target. Clinical monitoring of SIRS is challenging because of the narrow diagnostic window to institute a successful intervening therapeutic strategy prior to acute circulatory collapse. Furthermore, for these classes of therapeutic agents, studies in animals have low predictive ability to identify potential human hazards. In vitro screens with human cells, though promising, need further development. Therefore, identification of improved preclinical diagnostic markers of SIRS will enable clinicians to select applicable markers for clinical testing and avoid potentially catastrophic events. There is limited preclinical toxicology data describing the interspecies performance of acute-phase proteins because the response time, type, and duration of major acute-phase proteins vary significantly between species. This review will attempt to address this intellectual gap, as well as the use and applicability of acute-phase proteins as preclinical to clinical translational biomarkers of SIRS.

Characterization of acetate transport in colorectal cancer cells and potential therapeutic implications

PubMed Central

Ferro, Suellen; Azevedo-Silva, João; Casal, Margarida; Côrte-Real, Manuela; Baltazar, Fatima; Preto, Ana

2016-01-01

Acetate, together with other short chain fatty acids has been implicated in colorectal cancer (CRC) prevention/therapy. Acetate was shown to induce apoptosis in CRC cells. The precise mechanism underlying acetate transport across CRC cells membrane, that may be implicated in its selectivity towards CRC cells, is not fully understood and was addressed here. We also assessed the effect of acetate in CRC glycolytic metabolism and explored its use in combination with the glycolytic inhibitor 3-bromopyruvate (3BP). We provide evidence that acetate enters CRC cells by the secondary active transporters MCT1 and/or MCT2 and SMCT1 as well as by facilitated diffusion via aquaporins. CRC cell exposure to acetate upregulates the expression of MCT1, MCT4 and CD147, while promoting MCT1 plasma membrane localization. We also observed that acetate increases CRC cell glycolytic phenotype and that acetate-induced apoptosis and anti-proliferative effect was potentiated by 3BP. Our data suggest that acetate selectivity towards CRC cells might be explained by the fact that aquaporins and MCTs are found overexpressed in CRC clinical cases. Our work highlights the importance that acetate transport regulation has in the use of drugs such as 3BP as a new therapeutic strategy for CRC. PMID:28874966

Clinical Interpretation and Implications of Whole-Genome Sequencing

PubMed Central

Dewey, Frederick E.; Grove, Megan E.; Pan, Cuiping; Goldstein, Benjamin A.; Bernstein, Jonathan A.; Chaib, Hassan; Merker, Jason D.; Goldfeder, Rachel L.; Enns, Gregory M.; David, Sean P.; Pakdaman, Neda; Ormond, Kelly E.; Caleshu, Colleen; Kingham, Kerry; Klein, Teri E.; Whirl-Carrillo, Michelle; Sakamoto, Kenneth; Wheeler, Matthew T.; Butte, Atul J.; Ford, James M.; Boxer, Linda; Ioannidis, John P. A.; Yeung, Alan C.; Altman, Russ B.; Assimes, Themistocles L.; Snyder, Michael; Ashley, Euan A.; Quertermous, Thomas

2014-01-01

IMPORTANCE Whole-genome sequencing (WGS) is increasingly applied in clinical medicine and is expected to uncover clinically significant findings regardless of sequencing indication. OBJECTIVES To examine coverage and concordance of clinically relevant genetic variation provided by WGS technologies; to quantitate inherited disease risk and pharmacogenomic findings in WGS data and resources required for their discovery and interpretation; and to evaluate clinical action prompted by WGS findings. DESIGN, SETTING, AND PARTICIPANTS An exploratory study of 12 adult participants recruited at Stanford University Medical Center who underwent WGS between November 2011 and March 2012. A multidisciplinary team reviewed all potentially reportable genetic findings. Five physicians proposed initial clinical follow-up based on the genetic findings. MAIN OUTCOMES AND MEASURES Genome coverage and sequencing platform concordance in different categories of genetic disease risk, person-hours spent curating candidate disease-risk variants, interpretation agreement between trained curators and disease genetics databases, burden of inherited disease risk and pharmacogenomic findings, and burden and interrater agreement of proposed clinical follow-up. RESULTS Depending on sequencing platform, 10% to 19% of inherited disease genes were not covered to accepted standards for single nucleotide variant discovery. Genotype concordance was high for previously described single nucleotide genetic variants (99%-100%) but low for small insertion/deletion variants (53%-59%). Curation of 90 to 127 genetic variants in each participant required a median of 54 minutes (range, 5-223 minutes) per genetic variant, resulted in moderate classification agreement between professionals (Gross κ, 0.52; 95%CI, 0.40-0.64), and reclassified 69%of genetic variants cataloged as disease causing in mutation databases to variants of uncertain or lesser significance. Two to 6 personal disease-risk findings were discovered in each participant, including 1 frameshift deletion in the BRCA1 gene implicated in hereditary breast and ovarian cancer. Physician review of sequencing findings prompted consideration of a median of 1 to 3 initial diagnostic tests and referrals per participant, with fair interrater agreement about the suitability of WGS findings for clinical follow-up (Fleiss κ, 0.24; P < 001). CONCLUSIONS AND RELEVANCE In this exploratory study of 12 volunteer adults, the use of WGS was associated with incomplete coverage of inherited disease genes, low reproducibility of detection of genetic variation with the highest potential clinical effects, and uncertainty about clinically reportable findings. In certain cases, WGS will identify clinically actionable genetic variants warranting early medical intervention. These issues should be considered when determining the role of WGS in clinical medicine. PMID:24618965

"You Need to Be a Good Listener": Recruiters' Use of Relational Communication Behaviors to Enhance Clinical Trial and Research Study Accrual.

PubMed

Morgan, Susan E; Occa, Aurora; Potter, JoNell; Mouton, Ashton; Peter, Megan E

2017-02-01

Medical and research professionals who discuss clinical trials and research studies with potential participants face an often daunting challenge, particularly when recruiting from minority and underserved populations. This study reports on findings from a focus group study of 63 research coordinators, study nurses, professional recruiters, and other professionals in Indianapolis, IN and Miami, FL who work to recruit from minority and underserved populations. These professionals discussed the importance of creating a sense of connection with potential participants as part of the recruitment and retention process. Building a relationship, however fleeting, involved a number of concrete behaviors, including listening to personal information, expressing empathy, and then providing reciprocal self-disclosures; having repeated contact, usually by working in the same environment over an extended period of time; demonstrating respect through politeness and the use of honorifics; going the extra mile for participants; offering flexibility in scheduling follow-up appointments; and creating a sense of personal and community trust by being truthful. The implications of these findings for clinical trial and research study accrual are discussed.

Ex vivo lung perfusion: a comprehensive review of the development and exploration of future trends.

PubMed

Roman, Marius A; Nair, Sukumaran; Tsui, Steven; Dunning, John; Parmar, Jasvir S

2013-09-01

There is a critical mismatch between the number of donor lungs available and the demand for lungs for transplantation. This has created unacceptably high waiting-list mortality for lung transplant recipients. Currently (2012) in the United Kingdom, there are 216 patients on the lung transplant waiting list and 17 on heart and lung transplant list. The waiting times for suitable lungs average 412 days, with an increasing mortality and morbidity among the patients on the lung transplant list. Ex vivo lung perfusion (EVLP) has emerged as a technique for the assessment, resuscitation, and potential repair of suboptimal donor lungs. This is a rapidly developing field with significant clinical implications. In this review article, we critically appraise the background developments that have led to our current clinical practice. In particular, we focus on the human and animal experience, the different perfusion-ventilation strategies, and the impact of different perfusates and leukocyte filters. Finally, we examine EVLP as a potential research tool. This will provide insight into EVLP and its future development in the field of clinical lung transplantation.

Poppers: epidemiology and clinical management of inhaled nitrite abuse.

PubMed

Romanelli, Frank; Smith, Kelly M; Thornton, Alice C; Pomeroy, Claire

2004-01-01

Commonly referred to as "poppers," inhaled nitrites have a long history of abuse. Poppers are rapid-onset, short-acting potent vasodilators that produce a rush characterized by warm sensations and feelings of dizziness. Poppers sometimes are used to facilitate anal intercourse because of their actions on the anal sphincter. Epidemiologically, the frequent use of nitrites by men who have sex with men has led some experts to implicate these chemicals in the pathogenesis of Kaposi's sarcoma and acquired immunodeficiency syndrome. Controlled clinical trials to examine this potential correlation have not been conducted, and the use of nitrites simply may be a marker for other high-risk behaviors such as unprotected sex. Although regulated in the United States, many nitrite compounds and isomers are sold at various venues including bars, bookstores, and over the Internet. Adverse effects associated with these products vary from mild allergic reactions to life-threatening methemoglobinemia. The potential for drug-drug interactions and a propensity toward unsafe sex also exist. Clinicians should be familiar with the populations most likely to abuse these agents and with the clinical effects and management guidelines for acute ingestions.

DNA Repair in Prostate Cancer: Biology and Clinical Implications.

PubMed

Mateo, Joaquin; Boysen, Gunther; Barbieri, Christopher E; Bryant, Helen E; Castro, Elena; Nelson, Pete S; Olmos, David; Pritchard, Colin C; Rubin, Mark A; de Bono, Johann S

2017-03-01

For more precise, personalized care in prostate cancer (PC), a new classification based on molecular features relevant for prognostication and treatment stratification is needed. Genomic aberrations in the DNA damage repair pathway are common in PC, particularly in late-stage disease, and may be relevant for treatment stratification. To review current knowledge on the prevalence and clinical significance of aberrations in DNA repair genes in PC, particularly in metastatic disease. A literature search up to July 2016 was conducted, including clinical trials and preclinical basic research studies. Keywords included DNA repair, BRCA, ATM, CRPC, prostate cancer, PARP, platinum, predictive biomarkers, and hereditary cancer. We review how the DNA repair pathway is relevant to prostate carcinogenesis and progression. Data on how this may be relevant to hereditary cancer and genetic counseling are included, as well as data from clinical trials of PARP inhibitors and platinum therapeutics in PC. Relevant studies have identified genomic defects in DNA repair in PCs in 20-30% of advanced castration-resistant PC cases, a proportion of which are germline aberrations and heritable. Phase 1/2 clinical trial data, and other supporting clinical data, support the development of PARP inhibitors and DNA-damaging agents in this molecularly defined subgroup of PC following success in other cancer types. These studies may be an opportunity to improve patient care with personalized therapeutic strategies. Key literature on how genomic defects in the DNA damage repair pathway are relevant for prostate cancer biology and clinical management is reviewed. Potential implications for future changes in patient care are discussed. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Micro-RNAs as Potential Predictors of Response to Breast Cancer Systemic Therapy: Future Clinical Implications

PubMed Central

Campos-Parra, Alma D.; Cuamani Mitznahuatl, Gerardo; Pedroza-Torres, Abraham; Vázquez Romo, Rafael; Porras Reyes, Fany Iris; López-Urrutia, Eduardo; Pérez-Plasencia, Carlos

2017-01-01

Despite advances in diagnosis and new treatments such as targeted therapies, breast cancer (BC) is still the most prevalent tumor in women worldwide and the leading cause of death. The principal obstacle for successful BC treatment is the acquired or de novo resistance of the tumors to the systemic therapy (chemotherapy, endocrine, and targeted therapies) that patients receive. In the era of personalized treatment, several studies have focused on the search for biomarkers capable of predicting the response to this therapy; microRNAs (miRNAs) stand out among these markers due to their broad spectrum or potential clinical applications. miRNAs are conserved small non-coding RNAs that act as negative regulators of gene expression playing an important role in several cellular processes, such as cell proliferation, autophagy, genomic stability, and apoptosis. We reviewed recent data that describe the role of miRNAs as potential predictors of response to systemic treatments in BC. Furthermore, upon analyzing the collected published information, we noticed that the overexpression of miR-155, miR-222, miR-125b, and miR-21 predicts the resistance to the most common systemic treatments; nonetheless, the function of these particular miRNAs must be carefully studied and further analyses are still necessary to increase knowledge about their role and future potential clinical uses in BC. PMID:28574440

Micro-RNAs as Potential Predictors of Response to Breast Cancer Systemic Therapy: Future Clinical Implications.

PubMed

Campos-Parra, Alma D; Mitznahuatl, Gerardo Cuamani; Pedroza-Torres, Abraham; Romo, Rafael Vázquez; Reyes, Fany Iris Porras; López-Urrutia, Eduardo; Pérez-Plasencia, Carlos

2017-06-02

Despite advances in diagnosis and new treatments such as targeted therapies, breast cancer (BC) is still the most prevalent tumor in women worldwide and the leading cause of death. The principal obstacle for successful BC treatment is the acquired or de novo resistance of the tumors to the systemic therapy (chemotherapy, endocrine, and targeted therapies) that patients receive. In the era of personalized treatment, several studies have focused on the search for biomarkers capable of predicting the response to this therapy; microRNAs (miRNAs) stand out among these markers due to their broad spectrum or potential clinical applications. miRNAs are conserved small non-coding RNAs that act as negative regulators of gene expression playing an important role in several cellular processes, such as cell proliferation, autophagy, genomic stability, and apoptosis. We reviewed recent data that describe the role of miRNAs as potential predictors of response to systemic treatments in BC. Furthermore, upon analyzing the collected published information, we noticed that the overexpression of miR-155, miR-222, miR-125b, and miR-21 predicts the resistance to the most common systemic treatments; nonetheless, the function of these particular miRNAs must be carefully studied and further analyses are still necessary to increase knowledge about their role and future potential clinical uses in BC.

Practitioner Review: Multilingualism and neurodevelopmental disorders - an overview of recent research and discussion of clinical implications.

PubMed

Uljarević, Mirko; Katsos, Napoleon; Hudry, Kristelle; Gibson, Jenny L

2016-11-01

Language and communication skills are essential aspects of child development, which are often disrupted in children with neurodevelopmental disorders. Cutting edge research in psycholinguistics suggests that multilingualism has potential to influence social, linguistic and cognitive development. Thus, multilingualism has implications for clinical assessment, diagnostic formulation, intervention and support offered to families. We present a systematic review and synthesis of the effects of multilingualism for children with neurodevelopmental disorders and discuss clinical implications. We conducted systematic searches for studies on multilingualism in neurodevelopmental disorders. Keywords for neurodevelopmental disorders were based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition categories as follows; Intellectual Disabilities, Communication Disorders, Autism Spectrum Disorder (ASD), Attention-Deficit/Hyperactivity Disorder, Specific Learning Disorder, Motor Disorders, Other Neurodevelopmental Disorders. We included only studies based on empirical research and published in peer-reviewed journals. Fifty studies met inclusion criteria. Thirty-eight studies explored multilingualism in Communication Disorders, 10 in ASD and two in Intellectual Disability. No studies on multilingualism in Specific Learning Disorder or Motor Disorders were identified. Studies which found a disadvantage for multilingual children with neurodevelopmental disorders were rare, and there appears little reason to assume that multilingualism has negative effects on various aspects of functioning across a range of conditions. In fact, when considering only those studies which have compared a multilingual group with developmental disorders to a monolingual group with similar disorders, the findings consistently show no adverse effects on language development or other aspects of functioning. In the case of ASD, a positive effect on communication and social functioning has been observed. There is little evidence to support the widely held view that multilingual exposure is detrimental to the linguistic or social development of individuals with neurodevelopmental disorders. However, we also note that the available pool of studies is small and the number of methodologically high quality studies is relatively low. We discuss implications of multilingualism for clinical management of neurodevelopmental disorders, and discuss possible directions for future research. © 2016 Association for Child and Adolescent Mental Health.

Roles and Functions of Community Health Workers in Primary Care.

PubMed

Hartzler, Andrea L; Tuzzio, Leah; Hsu, Clarissa; Wagner, Edward H

2018-05-01

Community health workers have potential to enhance primary care access and quality, but remain underutilized. To provide guidance on their integration, we characterized roles and functions of community health workers in primary care through a literature review and synthesis. Analysis of 30 studies identified 12 functions (ie, care coordination, health coaching, social support, health assessment, resource linking, case management, medication management, remote care, follow-up, administration, health education, and literacy support) and 3 prominent roles representing clusters of functions: clinical services, community resource connections, and health education and coaching. We discuss implications for community health worker training and clinical support in primary care. © 2018 Annals of Family Medicine, Inc.

Magnetic resonance imaging based functional imaging in paediatric oncology.

PubMed

Manias, Karen A; Gill, Simrandip K; MacPherson, Lesley; Foster, Katharine; Oates, Adam; Peet, Andrew C

2017-02-01

Imaging is central to management of solid tumours in children. Conventional magnetic resonance imaging (MRI) is the standard imaging modality for tumours of the central nervous system (CNS) and limbs and is increasingly used in the abdomen. It provides excellent structural detail, but imparts limited information about tumour type, aggressiveness, metastatic potential or early treatment response. MRI based functional imaging techniques, such as magnetic resonance spectroscopy, diffusion and perfusion weighted imaging, probe tissue properties to provide clinically important information about metabolites, structure and blood flow. This review describes the role of and evidence behind these functional imaging techniques in paediatric oncology and implications for integrating them into routine clinical practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Canine distemper antibodies in lions of the Masai Mara.

PubMed

Kock, R; Chalmers, W S; Mwanzia, J; Chillingworth, C; Wambua, J; Coleman, P G; Baxendale, W

1998-06-13

Canine distemper virus (CDV) has been implicated in some recent deaths of lions, which showed clinical signs of distemper, in the the Serengeti plain. Similar clinical findings have since been reported in lions of the Masai Mara. Fifty-five per cent of serum samples obtained from wild lions of the Masai Mara have been found to contain neutralising antibody to CDV, indicating that they had been exposed to the virus. Adult orphan lions kept in captivity, were vaccinated with the live attenuated Onderstepoort strain of CDV. The results indicated that the vaccine is both safe and immunogenic, and may be potentially useful for the prophylactic vaccination of lions at high risk.

New Insights into the Pathogenesis of MDS and the rational therapeutic opportunities.

PubMed

Abou Zahr, Abdallah; Bernabe Ramirez, Carolina; Wozney, Jocelyn; Prebet, Thomas; Zeidan, Amer M

2016-01-01

Myelodysplastic syndromes (MDS) include a heterogeneous group of acquired hematopoietic malignancies characterized by ineffective hematopoiesis, peripheral cytopenias, and a varying propensity for progression to acute myeloid leukemia. The clinical heterogeneity in MDS is a reflection of its molecular heterogeneity. Better understanding of aberrant epigenetics, dysregulation of immune responses, and del(5q) MDS has provided the rationale for well-established treatments in MDS. Further understanding of abnormal signal transduction and aberrant apoptosis pathways has led to development of new rational therapies that are in advanced phases of clinical translation. This review seeks to describe recent developments in our understanding of the pathogenesis of MDS and the potential therapeutic implications of these observations.

Antenatal Breastfeeding Education and Support: Summary and Analysis of 2 Cochrane Publications.

PubMed

Jacobsen, Noelle

Key breastfeeding outcomes identified by the World Health Organization, the United Nations Children's Fund, the American Academy of Pediatrics, and Healthy People 2020 include early initiation, any such feeding at 6 months of age, and exclusivity. Broader themes in the current literature include infants who ever breastfed and overall duration. Healthcare providers need to know what current practices demonstrate effectiveness. A review of 2 Cochrane articles on which interventions impact these selected outcomes does not reveal any significant implications for clinical practice. Scant evidence exists to support any specific support efforts or educational outreach to improve these outcomes. A discussion of potential strategies to consider for future research and clinical practice is put forth.

A preliminary analysis of microRNA as potential clinical biomarker for schizophrenia.

PubMed

Sun, Xin-yang; Zhang, Jin; Niu, Wei; Guo, Wei; Song, Hong-tao; Li, Heng-yu; Fan, Hui-min; Zhao, Lin; Zhong, Ai-fang; Dai, Yun-hua; Guo, Zhong-min; Zhang, Li-yi; Lu, Jim; Zhang, Qiao-li

2015-04-01

MicroRNAs (miRNA, miR) have been implicated as promising blood-based biomarkers for schizophrenia patients. This study aimed to clinically validate miRNA as potential schizophrenia biomarkers. Plasma levels of 10 miRNAs were analyzed using qPCR in a cohort of 61 schizophrenia patients and 62 normal controls, as well as 25 patients particularly selected for a six-week antipsychotic treatment course. Positive And Negative Syndrome Scale (PANSS), Global Assessment Scale (GAS) and Clinical Global Impression (CGI) were administered to assess the clinical symptoms. The results demonstrated that a panel of miRNAs consisting of miR-30e, miR-181b, miR-34a, miR-346 and miR-7 had significantly increased expression levels with significant combined diagnostic value (AUC:0.713; sensitivity:35.5%; specificity:90.2%). In response to pharmacological treatment, expression levels of miR-132, miR-181b, miR-432 and miR-30e were significantly decreased. In addition, the improvement of clinical symptomatology was significantly correlated with the changes of miR-132, miR-181b, miR-212 and miR-30e expression levels. Furthermore, the decreases of plasma levels of miR-132 and miR-432 were significantly greater in high-effect subgroup than those in low-effect subgroup after six-week treatment course. We conclude that miR-30e, miR-181b, miR-34a, miR-346 and miR-7 combined as a panel are potentially useful non-invasive biomarkers for schizophrenia diagnosis. Markers miR-132, miR-181b, miR-30e and miR-432 are potential indicators for symptomatology improvements, treatment responses and prognosis for schizophrenia patients. © 2015 Wiley Periodicals, Inc.

Targeting kinase signaling pathways with constrained peptide scaffolds

PubMed Central

Hanold, Laura E.; Fulton, Melody D.; Kennedy, Eileen J.

2017-01-01

Kinases are amongst the largest families in the human proteome and serve as critical mediators of a myriad of cell signaling pathways. Since altered kinase activity is implicated in a variety of pathological diseases, kinases have become a prominent class of proteins for targeted inhibition. Although numerous small molecule and antibody-based inhibitors have already received clinical approval, several challenges may still exist with these strategies including resistance, target selection, inhibitor potency and in vivo activity profiles. Constrained peptide inhibitors have emerged as an alternative strategy for kinase inhibition. Distinct from small molecule inhibitors, peptides can provide a large binding surface area that allows them to bind shallow protein surfaces rather than defined pockets within the target protein structure. By including chemical constraints within the peptide sequence, additional benefits can be bestowed onto the peptide scaffold such as improved target affinity and target selectivity, cell permeability and proteolytic resistance. In this review, we highlight examples of diverse chemistries that are being employed to constrain kinase-targeting peptide scaffolds and highlight their application to modulate kinase signaling as well as their potential clinical implications. PMID:28185915

Structural neuroimaging across early-stage psychosis: Aberrations in neurobiological trajectories and implications for the staging model.

PubMed

Bartholomeusz, Cali F; Cropley, Vanessa L; Wannan, Cassandra; Di Biase, Maria; McGorry, Patrick D; Pantelis, Christos

2017-05-01

This review critically examines the structural neuroimaging evidence in psychotic illness, with a focus on longitudinal imaging across the first-episode psychosis and ultra-high-risk of psychosis illness stages. A thorough search of the literature involving specifically longitudinal neuroimaging in early illness stages of psychosis was conducted. The evidence supporting abnormalities in brain morphology and altered neurodevelopmental trajectories is discussed in the context of a clinical staging model. In general, grey matter (and, to a lesser extent, white matter) declines across multiple frontal, temporal (especially superior regions), insular and parietal regions during the first episode of psychosis, which has a steeper trajectory than that of age-matched healthy counterparts. Although the ultra-high-risk of psychosis literature is considerably mixed, evidence indicates that certain volumetric structural aberrations predate psychotic illness onset (e.g. prefrontal cortex thinning), while other abnormalities present in ultra-high-risk of psychosis populations are potentially non-psychosis-specific (e.g. hippocampal volume reductions). We highlight the advantages of longitudinal designs, discuss the implications such studies have on clinical staging and provide directions for future research.

Does Improving Patient-Practitioner Communication Improve Clinical Outcomes in Patients with Cardiovascular Diseases? A Systematic Review of the Evidence

PubMed Central

Schoenthaler, Antoinette; Kalet, Adina; Nicholson, Joseph; Lipkin, Mack

2014-01-01

Objective To conduct a systematic literature review appraising the effects of interventions to improve patient-practitioner communication on cardiovascular-related clinical outcomes. Methods Databases were searched up to March 27, 2013 to identify eligible studies that included interventions to improve patient and/or practitioner communication skills and assessment of a cardiovascular-related clinical outcome in adults ≥ 18 years of age. Results Fifteen papers were reviewed: The primary focus in seven studies was the patient; seven included a practitioner-focused intervention and one targeted both. Two patient-focused and two practitioner-focused studies demonstrated a beneficial effect of the intervention compared to a control group. Patient-focused studies were designed to improve patients’ information-seeking and question-asking skills with their practitioner. Practitioner-focused studies were designed to either improve practitioner’s general patient-centered communication or risk communication skills. Conclusions Few interventions targeting patient-practitioner communication have assessed the impact on cardiovascular-related clinical outcomes, limiting the ability to determine effectiveness. Additional rigorous research supported by theoretical frameworks and validated measurement is needed to understand the potential of patient-practitioner communication to improve cardiovascular-related clinical outcomes. Practice Implications Investments in communication skills trainings in medical education and practice are needed in order to attain the full potential of patient-centered care on cardiovascular-related clinical outcomes. Systematic Review Protocol Registration CRD42013006302 PMID:24795073

Implications of Parkinson's disease pathophysiology for the development of cell replacement strategies and drug discovery in neurodegenerative diseases.

PubMed

Pan-Montojo, Francisco; Funk, Richard H W

2012-11-01

Parkinson's disease (PD) is a progressive neurodegenerative disorder traditionally characterized by the loss of dopaminergic neurons in the substantia nigra (SN) at the midbrain. The potential use of adult or embryonic stem cells, induced pluriputent stem (iPS) cells and endogenous neurogenesis in cell replacement strategies has lead to numerous studies and clinical trials in this direction. It is now possible to differentiate stem cells into dopaminergic neurons in vitro and clinical trials have shown an improvement in PD-related symptoms after intra-striatal embryonic transplants and acceptable cell survival rates on the mid term. However, clinical improvement is transitory and associated with a strong placebo effect. Interestingly, recent pathological studies in PD patients who received embryonic stem cells show that in PD patients, grafted neurons show PD-related pathology. In this manuscript we review the latest findings regarding PD pathophysiology and give an outlook on the implications of these findings in how cell replacement strategies for PD treatment should be tested. These include changes in the type of animal models used, the preparation/conditioning of the cells before intracerebral injection, specially regarding backbone chronic diseases in iPS cells and determining the optimal proliferation, survival, differentiation and migration capacity of the grafted cells.

Approaches for targeting self-renewal pathways in cancer stem cells: implications for hematological treatments.

PubMed

Horne, Gillian A; Copland, Mhairi

2017-05-01

Self-renewal is considered a defining property of stem cells. Self-renewal is essential in embryogenesis and normal tissue repair and homeostasis. However, in cancer, self-renewal pathways, e.g. WNT, NOTCH, Hedgehog and BMP, frequently become de-regulated in stem cells, or more mature progenitor cells acquire self-renewal properties, resulting in abnormal tissue growth and tumorigenesis. Areas covered: This review considers the conserved embryonic self-renewal pathways, including WNT, NOTCH, Hedgehog and BMP. The article describes recent advances in our understanding of these pathways in leukemia and, more specifically, leukemia stem cells (LSC), how these pathways cross-talk and interact with the LSC microenvironment, and discusses the clinical implications and potential therapeutic strategies, both in preclinical and in clinical trials for hematological malignancies. Expert opinion: The conserved embryonic self-renewal pathways are frequently de-regulated in cancer stem cells (CSC), including LSCs. There is significant cross-talk between self-renewal pathways, and their downstream targets, and the microenvironment. Effective targeting of these pathways is challenging due to cross-talk, and importantly, because these pathways are important for normal stem cells as well as CSC, adverse effects on normal tissues may mean a therapeutic window cannot be identified. Nonetheless, several agents targeting these pathways are currently in clinical trials in hematological malignancies.

Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical implications.

PubMed

Kortekaas Krohn, I; Shikhagaie, M M; Golebski, K; Bernink, J H; Breynaert, C; Creyns, B; Diamant, Z; Fokkens, W J; Gevaert, P; Hellings, P; Hendriks, R W; Klimek, L; Mjösberg, J; Morita, H; Ogg, G S; O'Mahony, L; Schwarze, J; Seys, S F; Shamji, M H; Bal, S M

2018-04-01

Innate lymphoid cells (ILC) represent a group of lymphocytes that lack specific antigen receptors and are relatively rare as compared to adaptive lymphocytes. ILCs play important roles in allergic and nonallergic inflammatory diseases due to their location at barrier surfaces within the airways, gut, and skin, and they respond to cytokines produced by activated cells in their local environment. Innate lymphoid cells contribute to the immune response by the release of cytokines and other mediators, forming a link between innate and adaptive immunity. In recent years, these cells have been extensively characterized and their role in animal models of disease has been investigated. Data to translate the relevance of ILCs in human pathology, and the potential role of ILCs in diagnosis, as biomarkers and/or as future treatment targets are also emerging. This review, produced by a task force of the Immunology Section of the European Academy of Allergy and Clinical Immunology (EAACI), encompassing clinicians and researchers, highlights the role of ILCs in human allergic and nonallergic diseases in the airways, gastrointestinal tract, and skin, with a focus on new insights into clinical implications, therapeutic options, and future research opportunities. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Seizure clusters: characteristics and treatment.

PubMed

Haut, Sheryl R

2015-04-01

Many patients with epilepsy experience 'clusters' or flurries of seizures, also termed acute repetitive seizures (ARS). Seizure clustering has a significant impact on health and quality of life. This review summarizes recent advances in the definition and neurophysiologic understanding of clustering, the epidemiology and risk factors for clustering and both inpatient and outpatient clinical implications. New treatments for seizure clustering/ARS are perhaps the area of greatest recent progress. Efforts have focused on creating a uniform definition of a seizure cluster. In neurophysiologic studies of refractory epilepsy, seizures within a cluster appear to be self-triggering. Clinical progress has been achieved towards a more precise prevalence of clustering, and consensus guidelines for epilepsy monitoring unit safety. The greatest recent advances are in the study of nonintravenous route of benzodiazepines as rescue medications for seizure clusters/ARS. Rectal benzodiazepines have been very effective but barriers to use exist. New data on buccal, intramuscular and intranasal preparations are anticipated to lead to a greater number of approved treatments. Progesterone may be effective for women who experience catamenial clusters. Seizure clustering is common, particularly in the setting of medically refractory epilepsy. Clustering worsens health and quality of life, and the field requires greater focus on clarifying of definition and clinical implications. Progress towards the development of nonintravenous routes of benzodiazepines has the potential to improve care in this area.

Assessment and Treatment of Cognition and Communication Skills in Adults With Acquired Brain Injury via Telepractice: A Systematic Review.

PubMed

Coleman, Jaumeiko J; Frymark, Tobi; Franceschini, Nicole M; Theodoros, Deborah G

2015-05-01

This is a systematic review of assessment and treatment of cognitive and communicative abilities of individuals with acquired brain injury via telepractice versus in person. The a priori clinical questions were informed by previous research that highlights the importance of considering any functional implications of outcomes, determining disorder- and setting-specific concerns, and measuring the potential impact of diagnostic accuracy and treatment efficacy data on interpretation of findings. A literature search of multiple databases (e.g., PubMed) was conducted using key words and study inclusion criteria associated with the clinical questions. Ten group studies were accepted that addressed assessment of motor speech, language, and cognitive impairments; assessment of motor speech and language activity limitations/participation restrictions; and treatment of cognitive impairments and activity limitations/participation restrictions. In most cases, equivalence of outcomes was noted across service delivery methods. Limited findings, lack of diagnostic accuracy and treatment efficacy data, and heterogeneity of assessments and interventions precluded robust evaluation of clinical implications for telepractice equivalence and the broader area of telepractice efficacy. Future research is needed that will build upon current knowledge through replication. In addition, further evaluation at the impairment and activity limitation/participation restriction levels is needed.

Framing moving and handling as a complex healthcare intervention within the acute care of older people with osteoporosis: a qualitative study.

PubMed

Smith, Margaret Coulter; O'May, Fiona; Tropea, Savina; Berg, Jackie

2016-10-01

To investigate healthcare staff's views and experiences of caring for older hospitalised adults (aged 60+) with osteoporosis focusing on moving and handling. Specific objectives were to explore the composition of manual handling risk assessments and interventions in osteoporosis. Osteoporosis is a skeletal disease that reduces bone density and causes increased fracture risk. Incidence rises with age and osteoporotic fractures cause increased morbidity and mortality. It is a major global health problem. In the UK older hospitalised adults are normally screened for falls risk but not necessarily for osteoporosis. As presentation of osteoporosis is normally silent until fractures are evident, it is frequently undiagnosed. Healthcare staff's knowledge of osteoporosis is often suboptimal and specific manual handling implications are under-researched. An exploratory qualitative content analysis research design informed by critical realism. The purposive sample comprised 26 nursing and allied health professionals. Semi-structured interviews addressed topics including knowledge of osteoporosis, implications for acute care, moving and handling and clinical guidelines. Qualitative content data analysis was used. Awareness of osteoporosis prevalence in older populations varies and implications for nursing are indistinct to nonspecialists. In-hospital fractures potentially linked to suboptimal moving and handling seemed rare, but prospective studies are needed. Categories of 'Understanding moving and handling as routine care or as a healthcare intervention', with further categories 'healthcare practitioners' capacities and capabilities for dealing with people with osteoporosis' and 'the structural and organisational context for moving and handling' are reported alongside safety, frailty and dependency dimensions. This study informs moving and handling in higher risk groups such as osteoporosis. Clinical knowledge/expertise is required when adapting generic manual handling guidelines to specific patients/contexts. Patients' experiences of moving and handling have received limited attention. Increased focus on musculoskeletal conditions and moving and handling implications is required. © 2016 The Authors. Journal of Clinical Nursing Published by John Wiley & Sons Ltd.

Simplifying the complexity surrounding ICU work processes--identifying the scope for information management in ICU settings.

PubMed

Munir, Samina K; Kay, Stephen

2005-08-01

A multi-site study, conducted in two English and two Danish intensive care units, investigates the complexity of work processes in intensive care, and the implications of this complexity for information management with regards to clinical information systems. Data were collected via observations, shadowing of clinical staff, interviews and questionnaires. The construction of role activity diagrams enabled the capture of critical care work processes. Upon analysing these diagrams, it was found that intensive care work processes consist of 'simplified-complexity', these processes are changed with the introduction of information systems for the everyday use and management of all clinical information. The prevailing notion of complexity surrounding critical care clinical work processes was refuted and found to be misleading; in reality, it is not the work processes that cause the complexity, the complexity is rooted in the way in which clinical information is used and managed. This study emphasises that the potential for clinical information systems that consider integrating all clinical information requirements is not only immense but also very plausible.

Health issues of refugees attending an infectious disease refugee health clinic in a regional Australian hospital

PubMed

J Masters, Peta; J Lanfranco, Penelope; Sneath, Emmy; J Wade, Amanda; Huffam, Sarah; Pollard, James; Standish, James; McCloskey, Kate; Athan, Eugene; P O'Brien, Daniel; Friedman, N Deborah

2018-05-01

Refugees in Australia present with conditions different to those of the general population. The aim of this study was to review the reasons for referral, prevalence of conditions and treatment outcomes for refugee patients attending a specialist referral clinic in regional Victoria. A retrospective review was undertaken of patients attending the refugee health clinic at University Hospital Geelong from January 2007 to December 2012. Two hundred and ninety-one refugee patients attended the clinic over the six-year period. Latent tuberculosis infection (LTBI) (54.6%), vitamin deficiencies (15.8%), hepatitis B (11%) and schistosomiasis (11%) were the most common diagnoses. Less than two-thirds of the patients completed LTBI treatment; 35.4% of patients attended all scheduled clinic appointments. LTBI, vitamin deficiencies, parasitic infections and hepatitis B were the most common diagnoses among refugees referred to the University Hospital Geelong (UHG) Refugee Health Clinic from January 2007 to December 2012. General practitioners play an important role in the care of refugees, guiding referral to specialist services when necessary and recognising the potential implications of suboptimal clinic attendance and treatment completion.

Building a learning health system using clinical registers: a non-technical introduction.

PubMed

Ovretveit, John; Nelson, Eugene; James, Brent

2016-10-10

Purpose The purpose of this paper is to describe how clinical registers were designed and used to serve multiple purposes in three health systems, in order to contribute practical experience for building learning healthcare systems. Design/methodology/approach Case description and comparison of the development and use of clinical registries, drawing on participants' experience and published and unpublished research. Findings Clinical registers and new software systems enable fact-based decisions by patients, clinicians, and managers about better care, as well as new and more economical research. Designing systems to present the data for users' daily work appears to be the key to effective use of the potential afforded by digital data. Research limitations/implications The case descriptions draw on the experience of the authors who were involved in the development of the registers, as well as on published and unpublished research. There is limited data about outcomes for patients or cost-effectiveness. Practical implications The cases show the significant investments which are needed to make effective use of clinical register data. There are limited skills to design and apply the digital systems to make the best use of the systems and to reduce their disadvantages. More use can be made of digital data for quality improvement, patient empowerment and support, and for research. Social implications Patients can use their data combined with other data to self-manage their chronic conditions. There are challenges in designing and using systems so that those with lower health and computer literacy and incomes also benefit from these systems, otherwise the digital revolution may increase health inequalities. Originality/value The paper shows three real examples of clinical registers which have been developed as part of their host health systems' strategies to develop learning healthcare systems. The paper gives a simple non-technical introduction and overview for clinicians, managers, policy-advisors and improvers of what is possible and the challenges, and highlights the need to shape the design and implementation of digital infrastructures in healthcare services to serve users.

Comparison of glare in YAG-damaged intraocular lenses: injection-molded versus lathe-cut.

PubMed

Bath, P E; Dang, Y; Martin, W H

1986-11-01

A comparative analysis of YAG laser intraocular lens (IOL) damage was undertaken on injection-molded and lathe-cut IOLs. Damage sites were evaluated with polarized light. A consistent positive polarization was observed in the damage sites of lathe-cut IOLs. A consistent negative polarization was observed in the damage sites of injection-molded IOLs. The presence of positive polarization in IOL damage sites may be correlated with increased potential for glare. Results and clinical implications are discussed.

Pharmacogenetics of β-Blockers

PubMed Central

Shin, Jaekyu; Johnson, Julie A.

2009-01-01

β-Blockers are an important cardiovascular drug class, recommended as first-line treatment of numerous diseases such as heart failure, hypertension, and angina, as well as treatment after myocardial infarction. However, responses to a β-blocker are variable among patients. Results of numerous studies now suggest that genetic polymorphisms may contribute to variability in responses to β-blockers. This review summarizes the pharmacogenetic data for β-blockers in patients with various diseases and discusses the potential implications of β-blocker pharmacogenetics in clinical practice. PMID:17542770

Prognostic Value of Molecular Markers and Implication for Molecular Targeted Therapies in Nasopharyngeal Carcinoma: An Update in an Era of New Targeted Molecules Development.

PubMed

Liu, Mu-Tai; Chen, Mu-Kuan; Huang, Chia-Chun; Huang, Chao-Yuan

2015-02-01

The aim of the study was to evaluate the prognostic significance of molecular biomarkers which could provide information for more accurate prognostication and development of novel therapeutic strategies for nasopharyngeal carcinoma (NPC). NPC is a unique malignant epithelial carcinoma of head and neck region, with an intimate association with the Epstein-Barr virus (EBV). Currently, the prediction of NPC prognosis is mainly based on the clinical TNM staging; however, NPC patients with the same clinical stage often present different clinical outcomes, suggesting that the TNM stage is insufficient to precisely predict the prognosis of this disease. In this review, we give an overview of the prognostic value of molecular markers in NPC and discuss potential strategies of targeted therapies for treatment of NPC. Molecular biomarkers, which play roles in abnormal proliferation signaling pathways (such as Wnt/β-catenin pathway), intracellular mitogenic signal aberration (such as hypoxia-inducible factor (HIF)-1α), receptor-mediated aberrations (such as vascular endothelial growth factor (VEGF)), tumor suppressors (such as p16 and p27 activity), cell cycle aberrations (such as cyclin D1 and cyclin E), cell adhesion aberrations (such as E-cadherin), apoptosis dysregualtion (such as survivin) and centromere aberration (centromere protein H), are prognostic markers for NPC. Plasma EBV DNA concentrations and EBV-encoded latent membrane proteins are also prognostic markers for NPC. Implication of molecular targeted therapies in NPC was discussed. Such therapies could have potential in combination with different cytotoxic agents to combat and eradicate tumor cells. In order to further improve overall survival for patients with loco-regionally advanced NPC, the development of innovative strategies, including prognostic molecular markers and molecular targeted agents is needed.

Detection of cryptic pathogenic copy number variations and constitutional loss of heterozygosity using high resolution SNP microarray analysis in 117 patients referred for cytogenetic analysis and impact on clinical practice.

PubMed

Bruno, D L; Ganesamoorthy, D; Schoumans, J; Bankier, A; Coman, D; Delatycki, M; Gardner, R J M; Hunter, M; James, P A; Kannu, P; McGillivray, G; Pachter, N; Peters, H; Rieubland, C; Savarirayan, R; Scheffer, I E; Sheffield, L; Tan, T; White, S M; Yeung, A; Bowman, Z; Ngo, C; Choy, K W; Cacheux, V; Wong, L; Amor, D J; Slater, H R

2009-02-01

Microarray genome analysis is realising its promise for improving detection of genetic abnormalities in individuals with mental retardation and congenital abnormality. Copy number variations (CNVs) are now readily detectable using a variety of platforms and a major challenge is the distinction of pathogenic from ubiquitous, benign polymorphic CNVs. The aim of this study was to investigate replacement of time consuming, locus specific testing for specific microdeletion and microduplication syndromes with microarray analysis, which theoretically should detect all known syndromes with CNV aetiologies as well as new ones. Genome wide copy number analysis was performed on 117 patients using Affymetrix 250K microarrays. 434 CNVs (195 losses and 239 gains) were found, including 18 pathogenic CNVs and 9 identified as "potentially pathogenic". Almost all pathogenic CNVs were larger than 500 kb, significantly larger than the median size of all CNVs detected. Segmental regions of loss of heterozygosity larger than 5 Mb were found in 5 patients. Genome microarray analysis has improved diagnostic success in this group of patients. Several examples of recently discovered "new syndromes" were found suggesting they are more common than previously suspected and collectively are likely to be a major cause of mental retardation. The findings have several implications for clinical practice. The study revealed the potential to make genetic diagnoses that were not evident in the clinical presentation, with implications for pretest counselling and the consent process. The importance of contributing novel CNVs to high quality databases for genotype-phenotype analysis and review of guidelines for selection of individuals for microarray analysis is emphasised.

Whose decision is it anyway? How clinicians support decision-making participation after acquired brain injury.

PubMed

Knox, Lucy; Douglas, Jacinta M; Bigby, Christine

2013-01-01

To raise professional awareness of factors that may influence the support offered by clinicians to people with acquired brain injury (ABI), and to consider the potential implications of these factors in terms of post-injury rehabilitation and living. A review of the literature was conducted to identify factors that determine how clinicians provide support and influence opportunities for individuals with ABI to participate in decision making across the rehabilitation continuum. Clinical case studies are used to highlight two specific issues: (1) hidden assumptions on the part of the practitioner, and (2) perceptions of risk operating in clinical practice. There are a range of factors which may influence the decision-making support provided by clinicians and, ultimately, shape lifetime outcomes for individuals with ABI. A multidimensional framework may assist clinicians to identify relevant factors and consider their potential implications including those that influence how clinicians involved in supporting decision making approach this task. Participation in decision making is an undisputed human right and central to the provision of person-centred care. Further research is required to understand how clinical practice can maximise both opportunities and support for increased decision-making participation by individuals with ABI. There is an increasing focus on the rights of all individuals to be supported to participate in decision making about their life. A number of changes associated with ABI mean that individuals with ABI will require support with decision making. Clinicians have a critical role in providing this support over the course of the rehabilitation continuum. Clinicians need to be aware of the range of factors that may influence the decision-making support they provide. A multidimensional framework may be used by clinicians to identify influences on the decision-making support they provide.

Registered nurse and midwife experiences of using videoconferencing in practice: A systematic review of qualitative studies.

PubMed

Penny, Robyn A; Bradford, Natalie K; Langbecker, Danette

2018-03-01

To synthesise evidence of registered nurses' and midwives' experiences with videoconferencing and identify perceptions of the appropriateness, meaningfulness and feasibility of this technology in professional and clinical practice. Videoconferencing is a form of telehealth that can facilitate access to high-quality care to improve health outcomes for patients and enable clinicians working in isolation to access education, clinical supervision, peer support and case review. Yet use of videoconferencing has not translated smoothly into routine practice. Understanding the experiences of registered nurses and midwives may provide practitioners, service managers and policymakers with vital information to facilitate use of the technology. A qualitative meta-synthesis of primary qualitative studies undertaken according to Joanna Briggs Institute methodology. A systematic search of 19 databases was used to identify qualitative studies that reported on registered nurses' or midwives' experiences with videoconferencing in clinical or professional practice. Two reviewers independently appraised studies, extracted data and synthesised findings to construct core concepts. Nine studies met the criteria for inclusion. Five key synthesised findings were identified: useful on a continuum; broader range of information; implications for professional practice; barriers to videoconferencing; and technical support, training and encouragement. While videoconferencing offers benefits, it comes with personal, organisational and professional consequences for nurses and midwives. Understanding potential benefits and limitations, training and support required and addressing potential professional implications all influence adoption and ongoing use of videoconferencing. Registered nurses and midwives are well placed to drive innovations and efficiencies in practice such as videoconferencing. Nursing and midwifery practice must be reframed to adapt to the virtual environment while retaining valued aspects of professional practice. This includes ensuring professional standards keep pace with the development of knowledge in this area and addressing the findings highlighted in this meta-synthesis. © 2017 John Wiley & Sons Ltd.

Big-Data Based Decision-Support Systems to Improve Clinicians' Cognition.

PubMed

Roosan, Don; Samore, Matthew; Jones, Makoto; Livnat, Yarden; Clutter, Justin

2016-01-01

Complex clinical decision-making could be facilitated by using population health data to inform clinicians. In two previous studies, we interviewed 16 infectious disease experts to understand complex clinical reasoning. For this study, we focused on answers from the experts on how clinical reasoning can be supported by population-based Big-Data. We found cognitive strategies such as trajectory tracking, perspective taking, and metacognition has the potential to improve clinicians' cognition to deal with complex problems. These cognitive strategies could be supported by population health data, and all have important implications for the design of Big-Data based decision-support tools that could be embedded in electronic health records. Our findings provide directions for task allocation and design of decision-support applications for health care industry development of Big data based decision-support systems.

Big-Data Based Decision-Support Systems to Improve Clinicians’ Cognition

PubMed Central

Roosan, Don; Samore, Matthew; Jones, Makoto; Livnat, Yarden; Clutter, Justin

2016-01-01

Complex clinical decision-making could be facilitated by using population health data to inform clinicians. In two previous studies, we interviewed 16 infectious disease experts to understand complex clinical reasoning. For this study, we focused on answers from the experts on how clinical reasoning can be supported by population-based Big-Data. We found cognitive strategies such as trajectory tracking, perspective taking, and metacognition has the potential to improve clinicians’ cognition to deal with complex problems. These cognitive strategies could be supported by population health data, and all have important implications for the design of Big-Data based decision-support tools that could be embedded in electronic health records. Our findings provide directions for task allocation and design of decision-support applications for health care industry development of Big data based decision-support systems. PMID:27990498

Current perspectives on the epidemiology and pathogenesis of clinically significant Vibrio spp.

PubMed Central

Janda, J M; Powers, C; Bryant, R G; Abbott, S L

1988-01-01

Recent taxonomic advances have now implicated several different Vibrio species as human pathogens. While the most common clinical presentation of Vibrio infection continues to be gastroenteritis, an increasing number of extraintestinal infections are being reported, particularly in immunocompromised individuals. Detection of Vibrio infections requires a good clinical history and the use of appropriate isolation and identification procedures by the laboratory to confirm illnesses attributed to Vibrio species. Except for Vibrio cholerae O1 and Vibrio parahaemolyticus, there is little direct evidence linking the production of a myriad of cell-associated or extracellular factors produced by each species with human disease and pathogenesis. Many questions regarding pathogenic Vibrio species remain unanswered, including their frequency and distribution in environmental specimens (water, shellfish), infective doses, virulence potential of individual isolates, and markers associated with such strains. Images PMID:3058295

Clinical implications of genomic profiles in metastatic breast cancer with a focus on TP53 and PIK3CA, the most frequently mutated genes.

PubMed

Kim, Ji-Yeon; Lee, Eunjin; Park, Kyunghee; Park, Woong-Yang; Jung, Hae Hyun; Ahn, Jin Seok; Im, Young-Hyuck; Park, Yeon Hee

2017-04-25

Breast cancer (BC) has been genetically profiled through large-scale genome analyses. However, the role and clinical implications of genetic alterations in metastatic BC (MBC) have not been evaluated. Therefore, we conducted whole-exome sequencing (WES) and RNA-Seq of 37 MBC samples and targeted deep sequencing of another 29 MBCs. We evaluated somatic mutations from WES and targeted sequencing and assessed gene expression and performed pathway analysis from RNA-Seq. In this analysis, PIK3CA was the most commonly mutated gene in estrogen receptor (ER)-positive BC, while in ER-negative BC, TP53 was the most commonly mutated gene (p = 0.018 and p < 0.001, respectively). TP53 stopgain/loss and frameshift mutation was related to low expression of TP53 in contrast nonsynonymous mutation was related to high expression. The impact of TP53 mutation on clinical outcome varied with regard to ER status. In ER-positive BCs, wild type TP53 had a better prognosis than mutated TP53 (median overall survival (OS) (wild type vs. mutated): 88.5 ± 54.4 vs. 32.6 ± 10.7 (months), p = 0.002). In contrast, mutated TP53 had a protective effect in ER-negative BCs (median OS: 0.10 vs. 32.6 ± 8.2, p = 0.026). However, PIK3CA mutation did not affect patient survival. In gene expression analysis, CALM1, a potential regulator of AKT, was highly expressed in PIK3CA-mutated BCs. In conclusion, mutation of TP53 was associated with expression status and affect clinical outcome according to ER status in MBC. Although mutation of PIK3CA was not related to survival in this study, mutation of PIK3CA altered the expression of other genes and pathways including CALM1 and may be a potential predictive marker of PI3K inhibitor effectiveness.

Drug interactions between common illicit drugs and prescription therapies.

PubMed

Lindsey, Wesley T; Stewart, David; Childress, Darrell

2012-07-01

The aim was to summarize the clinical literature on interactions between common illicit drugs and prescription therapies. Medline, Iowa Drug Information Service, International Pharmaceutical Abstracts, EBSCO Academic Search Premier, and Google Scholar were searched from date of origin of database to March 2011. Search terms were cocaine, marijuana, cannabis, methamphetamine, amphetamine, ecstasy, N-methyl-3,4-methylenedioxymethamphetamine, methylenedioxymethamphetamine, heroin, gamma-hydroxybutyrate, sodium oxybate, and combined with interactions, drug interactions, and drug-drug interactions. This review focuses on established clinical evidence. All applicable full-text English language articles and abstracts found were evaluated and included in the review as appropriate. The interactions of illicit drugs with prescription therapies have the ability to potentiate or attenuate the effects of both the illicit agent and/or the prescription therapeutic agent, which can lead to toxic effects or a reduction in the prescription agent's therapeutic activity. Most texts and databases focus on theoretical or probable interactions due to the kinetic properties of the drugs and do not fully explore the pharmacodynamic and clinical implications of these interactions. Clinical trials with coadministration of illicit drugs and prescription drugs are discussed along with case reports that demonstrate a potential interaction between agents. The illicit drugs discussed are cocaine, marijuana, amphetamines, methylenedioxymethamphetamine, heroin, and sodium oxybate. Although the use of illicit drugs is widespread, there are little experimental or clinical data regarding the effects of these agents on common prescription therapies. Potential drug interactions between illicit drugs and prescription drugs are described and evaluated on the Drug Interaction Probability Scale by Horn and Hansten.

The incidence and severity of errors in pharmacist-written discharge medication orders.

PubMed

Onatade, Raliat; Sawieres, Sara; Veck, Alexandra; Smith, Lindsay; Gore, Shivani; Al-Azeib, Sumiah

2017-08-01

Background Errors in discharge prescriptions are problematic. When hospital pharmacists write discharge prescriptions improvements are seen in the quality and efficiency of discharge. There is limited information on the incidence of errors in pharmacists' medication orders. Objective To investigate the extent and clinical significance of errors in pharmacist-written discharge medication orders. Setting 1000-bed teaching hospital in London, UK. Method Pharmacists in this London hospital routinely write discharge medication orders as part of the clinical pharmacy service. Convenient days, based on researcher availability, between October 2013 and January 2014 were selected. Pre-registration pharmacists reviewed all discharge medication orders written by pharmacists on these days and identified discrepancies between the medication history, inpatient chart, patient records and discharge summary. A senior clinical pharmacist confirmed the presence of an error. Each error was assigned a potential clinical significance rating (based on the NCCMERP scale) by a physician and an independent senior clinical pharmacist, working separately. Main outcome measure Incidence of errors in pharmacist-written discharge medication orders. Results 509 prescriptions, written by 51 pharmacists, containing 4258 discharge medication orders were assessed (8.4 orders per prescription). Ten prescriptions (2%), contained a total of ten erroneous orders (order error rate-0.2%). The pharmacist considered that one error had the potential to cause temporary harm (0.02% of all orders). The physician did not rate any of the errors with the potential to cause harm. Conclusion The incidence of errors in pharmacists' discharge medication orders was low. The quality, safety and policy implications of pharmacists routinely writing discharge medication orders should be further explored.

Ketamine and phencyclidine: the good, the bad and the unexpected

PubMed Central

Lodge, D; Mercier, M S

2015-01-01

The history of ketamine and phencyclidine from their development as potential clinical anaesthetics through drugs of abuse and animal models of schizophrenia to potential rapidly acting antidepressants is reviewed. The discovery in 1983 of the NMDA receptor antagonist property of ketamine and phencyclidine was a key step to understanding their pharmacology, including their psychotomimetic effects in man. This review describes the historical context and the course of that discovery and its expansion into other hallucinatory drugs. The relevance of these findings to modern hypotheses of schizophrenia and the implications for drug discovery are reviewed. The findings of the rapidly acting antidepressant effects of ketamine in man are discussed in relation to other glutamatergic mechanisms. PMID:26075331

Outpatient clinic waiting time, provider communication styles and satisfaction with healthcare in India.

PubMed

Mehra, Payal

2016-08-08

Purpose - The purpose of this paper is to evaluate the impact of extended waiting time on patients' perceptions of provider communication skills and in-clinic satisfaction, in three major cities in India. Design/methodology/approach - In total, 625 patients were interviewed. The multivariate general linear model was used to determine the causality and relationship between the independent and the dependent variable. A moderation analysis was also conducted to assess waiting time role as a potential moderator in doctor-patient communication. Findings - Results show that patients with higher waiting time were less satisfied with health care quality. Male patients and patients of male providers were more affected by extended waiting time than female patients and patients of female providers. The advanced regression analysis, however, suggests weak support for waiting time and its effect on overall satisfaction with clinic quality. Waiting time did not moderate the relationship between satisfaction with dominant communication style, and overall satisfaction at the outpatient clinic. Research limitations/implications - A cross-sectional study does not easily lend itself to explaining causality with certainty. Thus, sophisticated techniques, such as structural equation modelling may also be utilized to assess the influence of extended waiting time on satisfaction with healthcare at outpatient clinics. Practical implications - Findings are relevant for providers as the onus is on them to ensure patient satisfaction. They should initiate a workable waiting time assessment model at the operational level. Originality/value - There has been a relatively lesser focus on patient waiting time in patient-provider satisfaction studies. In India, this aspect is still vastly unexplored especially in the context of outpatient clinics. Gender wise pattern of patient satisfaction and waiting time is also missing in most studies.

Economic impact of converting an interventional pain medicine physician office-based practice into a provider-based ambulatory pain practice.

PubMed

Grider, Jay S; Findley, Kelley A; Higdon, Courtney; Curtright, Jonathan; Clark, Don P

2014-01-01

One consequence of the shifting economic health care landscape is the growing trend of physician employment and practice acquisition by hospitals. These acquired practices are often converted into hospital- or provider-based clinics. This designation brings the increased services of the hospital, the accreditation of the hospital, and a new billing structure verses the private clinic (the combination of the facility and professional fee billing). One potential concern with moving to a provider-based designation is that this new structure might make the practice less competitive in a marketplace that may still be dominated by private physician office-based practices. The aim of the current study was to evaluate the impact of the provider-based/hospital fee structure on clinical volume. Determine the effect of transition to a hospital- or provider-based practice setting (with concomitant cost implications) on patient volume in the current practice milieu.   Community hospital-based academic interventional pain medicine practice. Economic analysis of effect of change in price structure on clinical volumes. The current study evaluates the effect of a change in designation with price implications on the demand for clinical services that accompany the transition to a hospital-based practice setting from a physician office setting in an academic community hospital. Clinical volumes of both procedures and clinic volumes increased in a mature practice setting following transition to a provider-based designation and the accompanying facility and professional fee structure. Following transition to a provider-based designation clinic visits were increased 24% while procedural volume demand did not change. Single practice entity and single geographic location in southeastern United States. The conversion to a hospital- or provider-based setting does not negatively impact clinical volume and referrals to community-based pain medicine practice. These results imply that factors other than price are a driver of patient choice.  

Repeated ischaemic preconditioning: a novel therapeutic intervention and potential underlying mechanisms.

PubMed

Thijssen, Dick H J; Maxwell, Joseph; Green, Daniel J; Cable, N Timothy; Jones, Helen

2016-06-01

What is the topic of this review? This review discusses the effects of repeated exposure of tissue to ischaemic preconditioning on cardiovascular function, the attendant adaptations and their potential clinical relevance. What advances does it highlight? We discuss the effects of episodic exposure to ischaemic preconditioning to prevent and/or attenuate ischaemic injury and summarize evidence pertaining to improvements in cardiovascular function and structure. Discussion is provided regarding the potential mechanisms that contribute to both local and systemic adaptation. Findings suggest that clinical benefits result from both the prevention of ischaemic events and the attenuation of their consequences. Ischaemic preconditioning (IPC) refers to the phenomenon whereby short periods of cyclical tissue ischaemia confer subsequent protection against ischaemia-induced injury. As a consequence, IPC can ameliorate the myocardial damage following infarction and can reduce infarct size. The ability of IPC to confer remote protection makes IPC a potentially feasible cardioprotective strategy. In this review, we discuss the concept that repeated exposure of tissue to IPC may increase the 'dose' of protection and subsequently lead to enhanced protection against ischaemia-induced myocardial injury. This may be relevant for clinical populations, who demonstrate attenuated efficacy of IPC to prevent or attenuate ischaemic injury (and therefore myocardial infarct size). Furthermore, episodic IPC facilitates repeated exposure to local (e.g. shear stress) and systemic stimuli (e.g. hormones, cytokines, blood-borne substances), which may induce improvement in vascular function and health. Such adaptation may contribute to prevention of cardio- and cerebrovascular events. The clinical benefits of repeated IPC may, therefore, result from both the prevention of ischaemic events and the attenuation of their consequences. We provide an overview of the literature pertaining to the impact of repeated IPC on cardiovascular function, related to both local and remote adaptation, as well as potential clinical implications. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

The physiological effects of slow breathing in the healthy human

PubMed Central

Russo, Marc A.; Santarelli, Danielle M.; O’Rourke, Dean

2017-01-01

Slow breathing practices have been adopted in the modern world across the globe due to their claimed health benefits. This has piqued the interest of researchers and clinicians who have initiated investigations into the physiological (and psychological) effects of slow breathing techniques and attempted to uncover the underlying mechanisms. The aim of this article is to provide a comprehensive overview of normal respiratory physiology and the documented physiological effects of slow breathing techniques according to research in healthy humans. The review focuses on the physiological implications to the respiratory, cardiovascular, cardiorespiratory and autonomic nervous systems, with particular focus on diaphragm activity, ventilation efficiency, haemodynamics, heart rate variability, cardiorespiratory coupling, respiratory sinus arrhythmia and sympathovagal balance. The review ends with a brief discussion of the potential clinical implications of slow breathing techniques. This is a topic that warrants further research, understanding and discussion. Key points Slow breathing practices have gained popularity in the western world due to their claimed health benefits, yet remain relatively untouched by the medical community. Investigations into the physiological effects of slow breathing have uncovered significant effects on the respiratory, cardiovascular, cardiorespiratory and autonomic nervous systems. Key findings include effects on respiratory muscle activity, ventilation efficiency, chemoreflex and baroreflex sensitivity, heart rate variability, blood flow dynamics, respiratory sinus arrhythmia, cardiorespiratory coupling, and sympathovagal balance. There appears to be potential for use of controlled slow breathing techniques as a means of optimising physiological parameters that appear to be associated with health and longevity, and that may extend to disease states; however, there is a dire need for further research into the area. Educational aims To provide a comprehensive overview of normal human respiratory physiology and the documented effects of slow breathing in healthy humans. To review and discuss the evidence and hypotheses regarding the mechanisms underlying slow breathing physiological effects in humans. To provide a definition of slow breathing and what may constitute “autonomically optimised respiration”. To open discussion on the potential clinical implications of slow breathing techniques and the need for further research. PMID:29209423

Th17 Cells Pathways in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders: Pathophysiological and Therapeutic Implications

PubMed Central

Passos, Giordani Rodrigues Dos; Sato, Douglas Kazutoshi; Becker, Jefferson; Fujihara, Kazuo

2016-01-01

Several animal and human studies have implicated CD4+ T helper 17 (Th17) cells and their downstream pathways in the pathogenesis of central nervous system (CNS) autoimmunity in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), challenging the traditional Th1-Th2 paradigm. Th17 cells can efficiently cross the blood-brain barrier using alternate ways from Th1 cells, promote its disruption, and induce the activation of other inflammatory cells in the CNS. A number of environmental factors modulate the activity of Th17 pathways, so changes in the diet, exposure to infections, and other environmental factors can potentially change the risk of development of autoimmunity. Currently, new drugs targeting specific points of the Th17 pathways are already being tested in clinical trials and provide basis for the development of biomarkers to monitor disease activity. Herein, we review the key findings supporting the relevance of the Th17 pathways in the pathogenesis of MS and NMOSD, as well as their potential role as therapeutic targets in the treatment of immune-mediated CNS disorders. PMID:26941483

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

Protein kinase CK2 modulates IL-6 expression in inflammatory breast cancer

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

Drygin, Denis, E-mail: ddrygin@cylenepharma.com; Ho, Caroline B.; Omori, Mayuko

Highlights: Black-Right-Pointing-Pointer We examine the potential cross-talk between CK2 and IL-6. Black-Right-Pointing-Pointer Inhibition of CK2 by siRNA or CX-4945 inhibits expression of IL-6 in models of IBC. Black-Right-Pointing-Pointer Treatment of IBC patient in the clinic with CX-4945 reduces her IL-6 plasma levels. Black-Right-Pointing-Pointer We demonstrate that CK2 is a potential therapeutic target for IL-6 driven diseases. -- Abstract: Inflammatory breast cancer is driven by pro-angiogenic and pro-inflammatory cytokines. One of them Interleukin-6 (IL-6) is implicated in cancer cell proliferation and survival, and promotes angiogenesis, inflammation and metastasis. While IL-6 has been shown to be upregulated by several oncogenes, the mechanismmore » behind this phenomenon is not well characterized. Here we demonstrate that the pleotropic Serine/Threonine kinase CK2 is implicated in the regulation of IL-6 expression in a model of inflammatory breast cancer. We used siRNAs targeted toward CK2 and a selective small molecule inhibitor of CK2, CX-4945, to inhibit the expression and thus suppress the secretion of IL-6 in in vitro as well as in vivo models. Moreover, we report that in a clinical trial, CX-4945 was able to dramatically reduce IL-6 levels in plasma of an inflammatory breast cancer patient. Our data shed a new light on the regulation of IL-6 expression and position CX-4945 and potentially other inhibitors of CK2, for the treatment of IL-6-driven cancers and possibly other diseases where IL-6 is instrumental, including rheumatoid arthritis.« less

Insights into potential pathogenesis mechanisms associated with Campylobacter jejuni-induced abortion in ewes.

PubMed

Sanad, Yasser M; Jung, Kwonil; Kashoma, Isaac; Zhang, Xiaoli; Kassem, Issmat I; Saif, Yehia M; Rajashekara, Gireesh

2014-11-25

Campylobacter jejuni is commonly found in the gastrointestinal tract of many food-animals including sheep without causing visible clinical symptoms of disease. However, C. jejuni has been implicated in ovine abortion cases worldwide. Specifically, in the USA, the C. jejuni sheep abortion (SA) clone has been increasingly associated with sheep abortion. In vivo studies in sheep (the natural host) are needed to better characterize the virulence potential and pathogenesis of this clone. Pregnant ewes intravenously (IV) or orally inoculated with ovine or bovine abortion-associated C. jejuni SA clones exhibited partial or complete uterine prolapse with retained placenta, and abortion or stillbirth, whereas delivery of healthy lambs occurred in pregnant ewes inoculated with C. jejuni 81-176 or in the uninfected group. In sheep inoculated with the SA clone, histopathological lesions including suppurative necrotizing placentitis and/or endometritis coincided with: 1) increased apoptotic death of trophoblasts, 2) increased expression of the host genes (e.g. genes encoding interleukin IL-6 and IL-15) related to cellular necrosis and pro-inflammatory responses in uterus, and 3) decreased expression of the genes encoding GATA binding protein 6, chordin, and insulin-like 3 (INSL3) that account for embryonic development in uterus. Immunohistochemistry revealed localization of bacterial antigens in trophoblasts lining the chorioallantoic membrane of ewes inoculated with the C. jejuni SA clone. The results showed that C. jejuni SA clones are capable of causing abortion or stillbirth in experimentally infected sheep. Furthermore, down- or up-regulation of specific genes in the uterus of infected pregnant ewes might implicate host genes in facilitating the disease progression. Since the C. jejuni SA strains share genotypic similarities with clones that have been isolated from human clinical cases of gastroenteritis, these strains might represent a potential public health risk.

Oxidative stress measured in vivo without an exogenous contrast agent using QUEST MRI

NASA Astrophysics Data System (ADS)

Berkowitz, Bruce A.

2018-06-01

Decades of experimental studies have implicated excessive generation of reactive oxygen species (ROS) in the decline of tissue function during normal aging, and as a pathogenic factor in a vast array of fatal or debilitating morbidities. This massive body of work has important clinical implications since many antioxidants are FDA approved, readily cross blood-tissue barriers, and are effective at improving disease outcomes. Yet, the potential benefits of antioxidants have remained largely unrealized in patients because conventional methods cannot determine the dose, timing, and drug combinations to be used in clinical trials to localize and decrease oxidative stress. To address this major problem and improve translational success, new methods are urgently needed that non-invasively measure the same ROS biomarker both in animal models and patients with high spatial resolution. Here, we summarize a transformative solution based on a novel method: QUEnch-assiSTed MRI (QUEST MRI). The QUEST MRI index is a significant antioxidant-induced improvement in pathophysiology, or a reduction in 1/T1 (i.e., R1). The latter form of QUEST MRI provides a unique measure of uncontrolled production of endogenous, paramagnetic reactive oxygen species (ROS). QUEST MRI results to-date have been validated by gold standard oxidative stress assays. QUEST MRI has high translational potential because it does not use an exogenous contrast agent and requires only standard MRI equipment. Summarizing, QUEST MRI is a powerful non-invasive approach with unprecedented potential for (i) bridging antioxidant treatment in animal models and patients, (ii) identifying tissue subregions exhibiting oxidative stress, and (iii) coupling oxidative stress localization with behavioral dysfunction, disease pathology, and genetic vulnerabilities to serve as a marker of susceptibility.

Discordance in histopathologic evaluation of melanoma sentinel lymph node biopsy with clinical follow-up: results from a prospectively collected database.

PubMed

Dandekar, Monisha; Lowe, Lori; Fullen, Douglas R; Johnson, Timothy M; Sabel, Michael S; Wong, Sandra L; Patel, Rajiv M

2014-10-01

Sentinel lymph node (SLN) status currently represents the single most important prognostic factor in clinically localized melanoma and is widely used in patients with melanoma at significant risk for nodal micrometastasis. Although several studies have looked at the rates and implications of inaccuracies in the histopathologic diagnosis of melanocytic lesions, accuracy in the histologic interpretation of the SLN in melanoma has not been addressed. The goal of this study was to determine the rates of discordance in the histopathologic evaluation of the SLN and the potential clinical impact on patients referred to a comprehensive melanoma center. A prospectively collected database was queried for melanoma patients who had SLN biopsies performed at outside institutions before referral to the University of Michigan Multidisciplinary Melanoma Program between 2006 and 2009. These cases were reviewed and clinical follow-up obtained. After internal review of the SLN material, 13 (8 %) of 167 cases had major discrepancies in diagnosis that impacted patient management and prognosis. The disease of five patients was subsequently downstaged and the disease of eight patients was upstaged after internal review of the SLNs and reversal in diagnoses. There appears to be a small yet significant rate of discordance in diagnosis of the SLN for melanoma after expert histopathologic review. The implications of this discordance and revision of diagnosis is substantial. Expert histopathologic review of the SLN warrants consideration to provide the most accurate prognostic information and optimal patient care.

A Decision Support Framework for Genomically Informed Investigational Cancer Therapy

PubMed Central

Johnson, Amber; Holla, Vijaykumar; Bailey, Ann Marie; Brusco, Lauren; Chen, Ken; Routbort, Mark; Patel, Keyur P.; Zeng, Jia; Kopetz, Scott; Davies, Michael A.; Piha-Paul, Sarina A.; Hong, David S.; Eterovic, Agda Karina; Tsimberidou, Apostolia M.; Broaddus, Russell; Bernstam, Elmer V.; Shaw, Kenna R.; Mendelsohn, John; Mills, Gordon B.

2015-01-01

Rapidly improving understanding of molecular oncology, emerging novel therapeutics, and increasingly available and affordable next-generation sequencing have created an opportunity for delivering genomically informed personalized cancer therapy. However, to implement genomically informed therapy requires that a clinician interpret the patient’s molecular profile, including molecular characterization of the tumor and the patient’s germline DNA. In this Commentary, we review existing data and tools for precision oncology and present a framework for reviewing the available biomedical literature on therapeutic implications of genomic alterations. Genomic alterations, including mutations, insertions/deletions, fusions, and copy number changes, need to be curated in terms of the likelihood that they alter the function of a “cancer gene” at the level of a specific variant in order to discriminate so-called “drivers” from “passengers.” Alterations that are targetable either directly or indirectly with approved or investigational therapies are potentially “actionable.” At this time, evidence linking predictive biomarkers to therapies is strong for only a few genomic markers in the context of specific cancer types. For these genomic alterations in other diseases and for other genomic alterations, the clinical data are either absent or insufficient to support routine clinical implementation of biomarker-based therapy. However, there is great interest in optimally matching patients to early-phase clinical trials. Thus, we need accessible, comprehensive, and frequently updated knowledge bases that describe genomic changes and their clinical implications, as well as continued education of clinicians and patients. PMID:25863335

The potential role of the medial olivocochlear bundle in the generation of tinnitus: controversies and weaknesses in the existing clinical studies.

PubMed

Riga, Maria; Katotomichelakis, Michael; Danielides, Vasilios

2015-02-01

The physiology of the efferent cochlear innervation and the pathophysiology of tinnitus are 2 important but rather obscure chapters of neuro-otology. The possible interference of the medial olivocochlear bundle (MOCB) in the pathophysiology of tinnitus is not only a matter of strong controversy but also a field with possible important clinical and therapeutic implications. The aim of this study was to reveal the differences in study population, design, and methodology that may have attributed the conflicting results in the existing clinical trials. A review of the relevant literature published between January 1990 and June 2013 was conducted via the PubMed database (www.pubmed.org) with the search terms "tinnitus" and "otoacoustic emissions and suppression or efferent." Clinical studies on patients with additional pathologic abnormalities that may implicate the MOCB, such as hyperacousis or auditory neuropathy, were excluded. The 15 relevant studies were reviewed for critical differences in the recruitment of their study population and control group, as well as their methods of testing and evaluating the results. The different methods and study parameters are compared to each other. Factors known to attribute different MOCB responses, possibly responsible for the controversial results, are highlighted. The remarkable heterogeneity of the existing studies does not allow for safe conclusions. Insufficient knowledge on the physiology of the MOCB reflex seems to preclude the formation of a consensus on the optimal protocol for the evaluation of its function. Further research is definitely needed.

F141. DUTY TO WARN FOR POTENTIAL RISK OF PSYCHOLOGICAL HARM: A CASE REPORT

PubMed Central

Zhand, Naista; Attwood, David

2018-01-01

Abstract Background Under the current ethical and legal standards physicians are expected to breach confidentiality when a third party is at risk. However, the law has mainly focused on risk of bodily harm and there is no legal guidance on physicians’ responsibilty when it comes to risk of psychological harm to a potential targeted victim Methods This case report illustrates a clinical dilemma on duty to warn for mental health professionals. Results N/A Discussion This case report illustrates an unconventional perspective on a psychiatrist’s duty to warn: consideration of risk of psychological harm to the potential target of their patient. Psychological trauma can have a potential negative impact on victims, affecting their mental health and well being as well as their physical health. The ethicolegal dilemma discussed in this case has implications for policies related to the care of psychiatric patients.

Potential mechanisms for chemotherapy-induced impairments in cognitive function.

PubMed

Jansen, Catherine; Miaskowski, Christine; Dodd, Marilyn; Dowling, Glenna; Kramer, Joel

2005-11-03

To review the domains of cognitive function and their corresponding neuroanatomic structures as well as present current evidence for neurotoxicity associated with specific chemotherapeutic agents and potential mechanisms for chemotherapy-induced cognitive impairments. Published research articles, review articles, and textbooks. Chemotherapy does not appear to cross the blood-brain barrier when given in standard doses; however, many chemotherapy drugs have the potential to cause cognitive impairments through more than one mechanism. In addition, patient factors may be protective or place individuals at higher risk for cognitive impairments. Although evidence of chemotherapy-induced impairments in cognitive function exists, no clinical studies have attempted to elucidate the mechanisms for chemotherapy-induced impairments in cognitive function. In addition, further studies are needed to determine predictive factors, potential biomarkers, and relevant assessment parameters. The ability to identify high-risk patients has important implications for practice in regard to informed consent, patient education about the effects of treatment, and preventive strategies.

Framing the research agenda for sickle cell trait: building on the current understanding of clinical events and their potential implications.

PubMed

Goldsmith, Jonathan C; Bonham, Vence L; Joiner, Clinton H; Kato, Gregory J; Noonan, Allan S; Steinberg, Martin H

2012-03-01

Sickle Cell Trait (HbAS), the heterozygous state for the sickle hemoglobin beta globin gene is carried by as many as 100 million individuals including up to 25% of the population in some regions of the world (World Health Organization, Provisional agenda item 4.8, EB117/34 (22 December 2005) or World Health Organization, Provisional agenda item 11.4 (24 April 2006)). Persons with HbAS have some resistance to falciparum malaria infection in early childhood (Piel FB, Patil AP, Howes RE, et al., Nat Commun 2010;1104:1-7 and Aidoo M, Terlouw DJ, Kolczak M, et al., Lancet 2002;359:1311-1312) and as a result individuals with HbAS living in malarial endemic regions of Africa have a survival advantage over individuals with HbAA. Reports from the US emphasize possible health risks for individuals with HbAS including increased incidence of renal failure and malignancy, thromboembolic disorders, splenic infarction as a high altitude complication, and exercise-related sudden death. The National Heart, Lung, and Blood Institute, National Institutes of Health convened a workshop in Bethesda, Maryland on June 3-4, 2010, Framing the Research Agenda for Sickle Cell Trait, to review the clinical manifestations of HbAS, discuss the exercise-related sudden death reports in HbAS, and examine the public health, societal, and ethical implications of policies regarding HbAS. The goal of the workshop was to identify potential research questions to address knowledge gaps.

Proteolytic roles of matrix metalloproteinase (MMP)-13 during progression of chronic periodontitis: initial evidence for MMP-13/MMP-9 activation cascade.

PubMed

Hernández Ríos, Marcela; Sorsa, Timo; Obregón, Fabián; Tervahartiala, Taina; Valenzuela, María Antonieta; Pozo, Patricia; Dutzan, Nicolás; Lesaffre, Emmanuel; Molas, Marek; Gamonal, Jorge

2009-12-01

Matrix metalloproteinases (MMP)-13 can initiate bone resorption and activate proMMP-9 in vitro, and both these MMPs have been widely implicated in tissue destruction associated with chronic periodontitis. We studied whether MMP-13 activity and TIMP-1 levels in gingival crevicular fluid (GCF) associated with progression of chronic periodontitis assessed clinically and by measuring carboxy-terminal telopeptide of collagen I (ICTP) levels. We additionally addressed whether MMP-13 could potentiate gelatinase activation in diseased gingival tissue. In this prospective study, GCF samples from subjects undergoing clinical progression of chronic periodontitis and healthy controls were screened for ICTP levels, MMP-13 activity and TIMP-1. Diseased gingival explants were cultured, treated or not with MMP-13 with or without adding CL-82198, a synthetic MMP-13 selective inhibitor, and assayed by gelatin zymography and densitometric analysis. Active sites demonstrated increased ICTP levels and MMP-13 activity (p<0.05) in progression subjects. The MMP-9 activation rate was elevated in MMP-13-treated explants (p<0.05) and MMP-13 inhibitor prevented MMP-9 activation. MMP-13 could be implicated in the degradation of soft and hard supporting tissues and proMMP-9 activation during progression of chronic periodontitis. MMP-13 and -9 can potentially form an activation cascade overcoming the protective TIMP-1 shield, which may become useful for diagnostic aims and a target for drug development.

"Still Rather Hazy at Present": Citizens' and Physicians' Views on Returning Results from Biobank Research Using Broad Consent.

PubMed

Barazzetti, Gaia; Cavalli, Samuele; Benaroyo, Lazare; Kaufmann, Alain

2017-03-01

Informed consent and return of research results are among the most debated topics in the biobank literature. We discuss ethical, social, and policy issues associated with returning results in the context of biobanks using a broad consent approach, in the light of data from a qualitative survey of citizens' and physicians' views. Data were collected through interviews and focus groups to investigate stakeholders' perspectives about a large-scale hospital-based biobank designed to foster biomedical research, including prospective genomics research, and "personalized" medicine. Both physicians and citizens considered psychosocial impacts as crucial in the assessment of benefits expected from a return of results to biobank participants. In particular, physicians highlighted the possible consequences on the patient-doctor relationship and discussed implications for the concept of "personalized" medicine. Citizens held ambivalent attitudes toward returning individual research results: they defended the "right not to know," while they also considered a sort of "responsibility to know" because of potential implications of results for family members. Moreover, physicians and citizens raised questions about the broad consent model used for inhospital biobank recruitment and expressed their needs for more training in genomics and more information on the biobank initiative. Stakeholders such as citizens and physicians, who may be concerned as potential biobank participants or as healthcare professionals involved in the management of clinically relevant research results, provide useful insights into several aspects of broad consent and return of results, related in particular to the interface between research and the clinic.

Validation of a metered dose inhaler electronic monitoring device: implications for asthma clinical trial use.

PubMed

Pilcher, Janine; Holliday, Mark; Ebmeier, Stefan; McKinstry, Steve; Messaoudi, Fatiha; Weatherall, Mark; Beasley, Richard

2016-01-01

The SmartTouch Ventolin monitor (Adherium, Auckland, New Zealand) is an electronic monitor for use with a Ventolin metered dose inhaler, which records the date and time of inhaler actuations. This technology has the potential to allow in-depth analysis of patterns of inhaler use in clinical trial settings. The aim of this study was to determine the accuracy of the SmartTouch Ventolin monitor in recording Ventolin actuations. 20 SmartTouch Ventolin monitors were attached to Ventolin metered dose inhalers. Bench testing was performed over a 10-week period, to reflect the potential time frame between visits in a clinical trial. Inhaler actuations were recorded in a paper diary, which was compared with data uploaded from the monitors. 2560 actuations were performed during the 10-week study period. Monitor sensitivity for diary-recorded actuations was 99.9% with a lower 97.5% confidence bound of 99.7%. The positive predictive value for diary-recorded actuations was 100% with a 97.5% lower confidence bound of 99.9%. The SmartTouch Ventolin monitor is highly accurate in recording and retaining electronic data. It can be recommended for use in clinical trial settings in which training and quality control systems are incorporated into study protocols to ensure accurate data acquisition.

Validation of a metered dose inhaler electronic monitoring device: implications for asthma clinical trial use

PubMed Central

Pilcher, Janine; Holliday, Mark; Ebmeier, Stefan; McKinstry, Steve; Messaoudi, Fatiha; Weatherall, Mark; Beasley, Richard

2016-01-01

Background The SmartTouch Ventolin monitor (Adherium, Auckland, New Zealand) is an electronic monitor for use with a Ventolin metered dose inhaler, which records the date and time of inhaler actuations. This technology has the potential to allow in-depth analysis of patterns of inhaler use in clinical trial settings. The aim of this study was to determine the accuracy of the SmartTouch Ventolin monitor in recording Ventolin actuations. Methods 20 SmartTouch Ventolin monitors were attached to Ventolin metered dose inhalers. Bench testing was performed over a 10-week period, to reflect the potential time frame between visits in a clinical trial. Inhaler actuations were recorded in a paper diary, which was compared with data uploaded from the monitors. Results 2560 actuations were performed during the 10-week study period. Monitor sensitivity for diary-recorded actuations was 99.9% with a lower 97.5% confidence bound of 99.7%. The positive predictive value for diary-recorded actuations was 100% with a 97.5% lower confidence bound of 99.9%. Conclusions The SmartTouch Ventolin monitor is highly accurate in recording and retaining electronic data. It can be recommended for use in clinical trial settings in which training and quality control systems are incorporated into study protocols to ensure accurate data acquisition. PMID:27026805

Combined-modality treatment of solid tumors using radiotherapy and molecular targeted agents.

PubMed

Ma, Brigette B Y; Bristow, Robert G; Kim, John; Siu, Lillian L

2003-07-15

Molecular targeted agents have been combined with radiotherapy (RT) in recent clinical trials in an effort to optimize the therapeutic index of RT. The appeal of this strategy lies in their potential target specificity and clinically acceptable toxicity. This article integrates the salient, published research findings into the underlying molecular mechanisms, preclinical efficacy, and clinical applicability of combining RT with molecular targeted agents. These agents include inhibitors of intracellular signal transduction molecules, modulators of apoptosis, inhibitors of cell cycle checkpoints control, antiangiogenic agents, and cyclo-oxygenase-2 inhibitors. Molecular targeted agents can have direct effects on the cytoprotective and cytotoxic pathways implicated in the cellular response to ionizing radiation (IR). These pathways involve cellular proliferation, DNA repair, cell cycle progression, nuclear transcription, tumor angiogenesis, and prostanoid-associated inflammation. These pathways can also converge to alter RT-induced apoptosis, terminal growth arrest, and reproductive cell death. Pharmacologic modulation of these pathways may potentially enhance tumor response to RT though inhibition of tumor repopulation, improvement of tumor oxygenation, redistribution during the cell cycle, and alteration of intrinsic tumor radiosensitivity. Combining RT and molecular targeted agents is a rational approach in the treatment of solid tumors. Translation of this approach from promising preclinical data to clinical trials is actively underway.

Concise Review: Mesenchymal Stem Cell Therapy for Pediatric Disease: Perspectives on Success and Potential Improvements

PubMed Central

Nitkin, Christopher R.

2016-01-01

Abstract Mesenchymal stem cells (MSCs) represent a potentially revolutionary therapy for a wide variety of pediatric diseases, but the optimal cell‐based therapeutics for such diversity have not yet been specified. The published clinical trials for pediatric pulmonary, cardiac, orthopedic, endocrine, neurologic, and hematologic diseases provide evidence that MSCs are indeed efficacious, but the significant heterogeneity in therapeutic approaches between studies raises new questions. The purpose of this review is to stimulate new preclinical and clinical trials to investigate these factors. First, we discuss recent clinical trials for pediatric diseases studying MSCs obtained from bone marrow, umbilical cord and umbilical cord blood, placenta, amniotic fluid, and adipose tissue. We then identify factors, some unique to pediatrics, which must be examined to optimize therapeutic efficacy, including route of administration, dose, timing of administration, the role of ex vivo differentiation, cell culture techniques, donor factors, host factors, and the immunologic implications of allogeneic therapy. Finally, we discuss some of the practicalities of bringing cell‐based therapy into the clinic, including regulatory and manufacturing considerations. The aim of this review is to inform future studies seeking to maximize therapeutic efficacy for each disease and for each patient. Stem Cells Translational Medicine 2017;6:539–565 PMID:28191766

Can probiotics enhance vaccine-specific immunity in children and adults?

PubMed

Kwak, J Y; Lamousé-Smith, E S N

2017-10-13

The growing use of probiotics by the general public has heightened the interest in understanding the role of probiotics in promoting health and preventing disease. General practitioners and specialists often receive inquiries from their patients regarding probiotic products and their use to ward off systemic infection or intestinal maladies. Enhanced immune function is among the touted health benefits conferred by probiotics but has not yet been fully established. Results from recent clinical trials in adults suggest a potential role for probiotics in enhancing vaccine-specific immunity. Although almost all vaccinations are given during infancy and childhood, the numbers of and results from studies using probiotics in pediatric subjects are limited. This review evaluates recent clinical trials of probiotics used to enhance vaccine-specific immune responses in adults and infants. We highlight meaningful results and the implications of these findings for designing translational and clinical studies that will evaluate the potential clinical role for probiotics. We conclude that the touted health claims of probiotics for use in children to augment immunity warrant further investigation. In order to achieve this goal, a consensus should be reached on common study designs that apply similar treatment timelines, compare well-characterised probiotic strains and monitor effective responses against different classes of vaccines.

Fermentation products in the cystic fibrosis airways induce aggregation and dormancy-associated expression profiles in a CF clinical isolate of Pseudomonas aeruginosa

PubMed Central

Phan, Joann; Gallagher, Tara; Oliver, Andrew; England, Whitney E; Whiteson, Katrine

2018-01-01

Abstract Pseudomonas aeruginosa is a well-known dominant opportunistic pathogen in cystic fibrosis (CF) with a wide range of metabolic capacities. However, P. aeruginosa does not colonize the airways alone, and benefits from the metabolic products of neighboring cells—especially volatile molecules that can travel between different parts of the airways easily. Here, we present a study that investigates the metabolic, gene expression profiles and phenotypic responses of a P. aeruginosa clinical isolate to fermentation products lactic acid and 2,3-butanediol, metabolites that are produced by facultative anaerobic members of the CF polymicrobial community and potential biomarkers of disease progression. Although previous studies have successfully investigated the metabolic and transcriptional profiles of P. aeruginosa, most have used common lab reference strains that may differ in important ways from clinical isolates. Using transcriptomics and metabolomics with gas chromatography time of flight mass spectrometry, we observe that fermentation products induce pyocyanin production along with the expression of genes involved in P. aeruginosa amino acid utilization, dormancy and aggregative or biofilm modes of growth. These findings have important implications for how interactions within the diverse CF microbial community influence microbial physiology, with potential clinical consequences. PMID:29617986

Intelligent Assistive Technology for Alzheimer's Disease and Other Dementias: A Systematic Review.

PubMed

Ienca, Marcello; Fabrice, Jotterand; Elger, Bernice; Caon, Maurizio; Pappagallo, Alessandro Scoccia; Kressig, Reto W; Wangmo, Tenzin

2017-01-01

Intelligent assistive technologies (IATs) have the potential of offering innovative solutions to mitigate the global burden of dementia and provide new tools for dementia care. While technological opportunities multiply rapidly, clinical applications are rare as the technological potential of IATs remains inadequately translated into dementia care. In this article, the authors present the results of a systematic review and the resulting comprehensive technology index of IATs with application in dementia care. Computer science, engineering, and medical databases were extensively searched and the retrieved items were systematically reviewed. For each IAT, the authors examined their technological type, application, target population, model of development, and evidence of clinical validation. The findings reveal that the IAT spectrum is expanding rapidly in volume and variety over time, and encompasses intelligent systems supporting various assistive tasks and clinical uses. At the same time, the results confirm the persistence of structural limitations to successful adoption including partial lack of clinical validation and insufficient focus on patients' needs. This index is designed to orient clinicians and relevant stakeholders involved in the implementation and management of dementia care across the current capabilities, applications, and limitations of IATs and to facilitate the translation of medical engineering research into clinical practice. In addition, a discussion of the major methodological challenges and policy implications for the successful and ethically responsible implementation of IAT into dementia care is provided.

Views of potential research participants on financial conflicts of interest: barriers and opportunities for effective disclosure.

PubMed

Weinfurt, Kevin P; Friedman, Joëlle Y; Allsbrook, Jennifer S; Dinan, Michaela A; Hall, Mark A; Sugarman, Jeremy

2006-09-01

There is little guidance regarding how to disclose researchers' financial interests to potential research participants. To determine what potential research participants want to know about financial interests, their capacity to understand disclosed information and its implications, and the reactions of potential research participants to a proposed disclosure statement. Sixteen focus groups in 3 cities, including 6 groups of healthy adults, 6 groups of adults with mild chronic illness, 1 group of parents of healthy children, 1 group of parents of children with leukemia or brain tumor, 1 group of adults with heart failure, and 1 group of adults with cancer. Focus group discussions covered a range of topics including financial relationships in clinical research, whether people should be told about them, and how they should be told. Audio-recordings of focus groups were transcribed, verified, and coded for analysis. Participants wanted to know about financial interests, whether or not those interests would affect their participation. However, they varied in their desire and ability to understand the nature and implications of financial interests. Whether disclosure was deemed important depended upon the risk of the research. Trust in clinicians was also related to views regarding disclosure. If given the opportunity to ask questions during the consent process, some participants would not have known what to ask; however, after the focus group sessions, participants could identify information they would want to know. Financial interests are important to potential research participants, but obstacles to effective disclosure exist.

Waldenstrom’s Macroglobulinemia: An Update

PubMed Central

Mazzucchelli, Maddalena; Frustaci, Anna Maria; Deodato, Marina; Cairoli, Roberto; Tedeschi, Alessandra

2018-01-01

Waldenstrom Macroglobulinemia is a rare lymphoproliferative disorder with distinctive clinical features. Diagnostic and prognostic characterisation in WM significantly changed with the discovery of two molecular markers: MYD88 and CXCR4. Mutational status of these latter influences both clinical presentation and prognosis and demonstrated therapeutic implications. Treatment choice in Waldenstrom disease is strictly guided by patients age and characteristics, specific goals of therapy, the necessity for rapid disease control, the risk of treatment-related neuropathy, disease features, the risk of immunosuppression or secondary malignancies and potential for future autologous stem cell transplantation. The therapeutic landscape has expanded during the last years and the approval of ibrutinib, the first drug approved for Waldenstrom Macroglobulinemia, represents a significant step forward for a better management of the disease. PMID:29326801

Major Developments in the Design of Inhibitors along the Kynurenine Pathway

PubMed Central

Jacobs, Kelly R.; Castellano-González, Gloria; Guillemin, Gilles J.; Lovejoy, David B.

2017-01-01

Disrupted kynurenine pathway (KP) metabolism has been implicated in the progression of neurodegenerative disease, psychiatric disorders and cancer. Modulation of enzyme activity along this pathway may therefore offer potential new therapeutic strategies for these conditions. Considering their prominent positions in the KP, the enzymes indoleamine 2,3-dioxygenase, kynurenine 3-monooxygenase and kynurenine aminotransferase, appear the most attractive targets. Already, increasing interest in this pathway has led to the identification of a number of potent and selective enzyme inhibitors with promising pre-clinical data and the elucidation of several enzyme crystal structures provides scope to rationalize the molecular mechanisms of inhibitor activity. The field seems poised to yield one or more inhibitors that should find clinical utility. PMID:28464785

The 2015 US Food and Drug Administration Pregnancy and Lactation Labeling Rule.

PubMed

Brucker, Mary C; King, Tekoa L

2017-05-01

As of 2015, the US Food and Drug Administration (FDA) discontinued the pregnancy risk categories (ABCDX) that had been used to denote the putative safety of drugs for use among pregnant women. The ABCDX system has been replaced by the FDA Pregnancy and Lactation Labeling Rule (PLLR) that requires narrative text to describe risk information, clinical considerations, and background data for the drug. The new rule includes 3 overarching categories: 1) pregnancy, which includes labor and birth; 2) lactation; and 3) females and males of reproductive potential. This article reviews the key components of the PLLR and clinical implications, and provides resources for clinicians who prescribe drugs for women of reproductive age. © 2017 by the American College of Nurse-Midwives.

The entry-level occupational therapy clinical doctorate: advantages, challenges, and international issues to consider.

PubMed

Brown, Ted; Crabtree, Jeffrey L; Mu, Keli; Wells, Joe

2015-04-01

Internationally, occupational therapy education has gone through several paradigm shifts during the last few decades, moving from certificate to diploma to bachelors to masters and now in some instances to clinical doctorate as the entry-level professional credential to practice. In the United States there is a recommendation under consideration by the American Occupational Therapy Association (AOTA) that by 2025, all occupational therapy university programs will move to the clinical doctorate level. It should be noted, however, that the AOTA Board can only make recommendations and it is the Accreditation Council for Occupational Therapy Education (ACOTE) who has regulatory authority to approve such a change. What are the potential implications for the profession, our clients, and funders of occupational therapy services? What are the primary drivers for the move towards the clinical doctorate being the educational entry point? Is the next step in the evolution of occupational therapy education globally a shift to the entry-level clinical doctorate? This article reviews current literature and discusses issues about the occupational therapy entry-level clinical doctorate. The published evidence available about the occupational therapy entry-level clinical doctorate is summarized and the perceived or frequently cited pros and cons of moving to the clinical doctorate as the singular entry point to occupational therapy practice are considered. The potential impacts of the introduction of the clinical doctorate as the entry-to-practice qualification across the United States on the occupational therapy community internationally will be briefly discussed. If the United States moves toward the entry-level clinical doctorate as the only educational starting point for the profession, will other jurisdictions follow suit? Further discourse and investigation of this issue both inside and outside of the United States is needed so that informed decisions can be made.

Transfer of communication skills training from workshop to workplace: the impact of clinical supervision.

PubMed

Heaven, Cathy; Clegg, Jenny; Maguire, Peter

2006-03-01

Recent studies have recognised that the communication skills learned in the training environment are not always transferred back into the clinical setting. This paper reports a study which investigated the potential of clinical supervision in enhancing the transfer process. A randomised controlled trial was conducted involving 61 clinical nurse specialists. All attended a 3-day communication skills training workshop. Twenty-nine were then randomised to 4 weeks of clinical supervision, aimed at facilitating transfer of newly acquired skills into practice. Assessments, using real and simulated patients, were carried out before the course, immediately after the supervision period and 3 months later. Interviews were rated objectively using the Medical Interview Aural Rating Scale (MIARS) to assess nurses' ability to use key skills, respond to patient cues and identify patient concerns. Assessments with simulated patients showed that the training programme was extremely effective in changing competence in all three key areas. However, only those who experienced supervision showed any evidence of transfer. Improvements were found in the supervised groups' use of open questions, negotiation and psychological exploration. Whilst neither group facilitated more disclosure of cues or concerns, those in the experimental group responded more effectively to the cues disclosed, reduced their distancing behaviour and increasing their exploration of cues. The study has shown that whilst training enhances skills, without intervention, it may have little effect on clinical practice. The potential role of clinical supervision as one way of enhancing the clinical effectiveness of communication skills training programmes has been demonstrated. PRACTISE IMPLICATIONS: This study raises questions about the effectiveness of training programmes which do not incorporate a transfer element, and provides evidence to support the need for clinical supervision for clinical nurse specialist.

Future of electronic health records: implications for decision support.

PubMed

Rothman, Brian; Leonard, Joan C; Vigoda, Michael M

2012-01-01

The potential benefits of the electronic health record over traditional paper are many, including cost containment, reductions in errors, and improved compliance by utilizing real-time data. The highest functional level of the electronic health record (EHR) is clinical decision support (CDS) and process automation, which are expected to enhance patient health and healthcare. The authors provide an overview of the progress in using patient data more efficiently and effectively through clinical decision support to improve health care delivery, how decision support impacts anesthesia practice, and how some are leading the way using these systems to solve need-specific issues. Clinical decision support uses passive or active decision support to modify clinician behavior through recommendations of specific actions. Recommendations may reduce medication errors, which would result in considerable savings by avoiding adverse drug events. In selected studies, clinical decision support has been shown to decrease the time to follow-up actions, and prediction has proved useful in forecasting patient outcomes, avoiding costs, and correctly prompting treatment plan modifications by clinicians before engaging in decision-making. Clinical documentation accuracy and completeness is improved by an electronic health record and greater relevance of care data is delivered. Clinical decision support may increase clinician adherence to clinical guidelines, but educational workshops may be equally effective. Unintentional consequences of clinical decision support, such as alert desensitization, can decrease the effectiveness of a system. Current anesthesia clinical decision support use includes antibiotic administration timing, improved documentation, more timely billing, and postoperative nausea and vomiting prophylaxis. Electronic health record implementation offers data-mining opportunities to improve operational, financial, and clinical processes. Using electronic health record data in real-time for decision support and process automation has the potential to both reduce costs and improve the quality of patient care. © 2012 Mount Sinai School of Medicine.

Battery-free, wireless sensors for full-body pressure and temperature mapping.

PubMed

Han, Seungyong; Kim, Jeonghyun; Won, Sang Min; Ma, Yinji; Kang, Daeshik; Xie, Zhaoqian; Lee, Kyu-Tae; Chung, Ha Uk; Banks, Anthony; Min, Seunghwan; Heo, Seung Yun; Davies, Charles R; Lee, Jung Woo; Lee, Chi-Hwan; Kim, Bong Hoon; Li, Kan; Zhou, Yadong; Wei, Chen; Feng, Xue; Huang, Yonggang; Rogers, John A

2018-04-04

Thin, soft, skin-like sensors capable of precise, continuous measurements of physiological health have broad potential relevance to clinical health care. Use of sensors distributed over a wide area for full-body, spatiotemporal mapping of physiological processes would be a considerable advance for this field. We introduce materials, device designs, wireless power delivery and communication strategies, and overall system architectures for skin-like, battery-free sensors of temperature and pressure that can be used across the entire body. Combined experimental and theoretical investigations of the sensor operation and the modes for wireless addressing define the key features of these systems. Studies with human subjects in clinical sleep laboratories and in adjustable hospital beds demonstrate functionality of the sensors, with potential implications for monitoring of circadian cycles and mitigating risks for pressure-induced skin ulcers. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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

Non-coding RNAs in Prostate Cancer: From Discovery to Clinical Applications.

PubMed

Ceder, Yvonne

2016-01-01

Prostate cancer is a heterogeneous disease for which the molecular mechanisms are still not fully elucidated. Prostate cancer research has traditionally focused on genomic and epigenetic alterations affecting the proteome, but over the last decade non-coding RNAs, especially microRNAs, have been recognized to play a key role in prostate cancer progression. A considerable number of individual microRNAs have been found to be deregulated in prostate cancer and their biological significance elucidated in functional studies. This review will delineate the current advances regarding the involvement of microRNAs and their targets in prostate cancer biology as well as their potential usage in the clinical management of the disease. The main focus will be on microRNAs contributing to initiation and progression of prostate cancer, including androgen signalling, cellular plasticity, stem cells biology and metastatic processes. To conclude, implications on potential future microRNA-based therapeutics based on the recent advances regarding the interplay between microRNAs and their targets are discussed.

Neural Implications of Psychotherapy, Pharmacotherapy, and Combined Treatment in Major Depressive Disorder

PubMed Central

Schwartz, Thomas L.; Santarsieri, Daniel

2016-01-01

Numerous clinical trials have been conducted to determine the utility of antidepressant treatment (ADT), psychotherapy, and combined psycho-pharmaco-psychotherapy (PPPT) in treating major depressive disorder (MDD). While all approaches have shown benefit over placebo to varying degrees, the parallel neurophysiological mechanisms that underlie their efficacy have received little attention. The authors will review and discuss a growing body of literature that relates the factors of treatment selection and response to the principles of neuromodulation, with emphasis regarding how neuroimaging and other experimental data reinforce the need for personalized MDD treatment. This manuscript and its theoretical approaches were supported by conducting relevant literature searches of MEDLINE and PubMed electronic databases, prioritizing systemic reviews, and randomized clinical trials using selected MeSH terms. The authors conclude that ADT, psychotherapy, and PPPT all create potentially observable neurofunctional changes and argue that additive and synergistic potentiation of these effects in PPPT may produce more sustained symptom relief than with monotherapy alone. PMID:28031623

The roles of safety and compliance in determining effectiveness of topical therapy for psoriasis.

PubMed

Stein Gold, Linda; Corvari, Linda

2007-01-01

Topical therapies are the mainstays of treatment for most patients with psoriasis because they relieve symptoms and reduce the size and severity of lesions. The effectiveness of a therapeutic intervention is a function of drug efficacy (determined by randomized clinical trial results) and patient safety and compliance. Alterations in any parameter can have a substantial influence on clinical outcomes. However, topical agents can be associated with unwanted and potentially toxic side effects that make physicians reluctant to prescribe them, and patients intentionally discontinue treatment with these topical agents. To maximize effectiveness and improve patient safety, physicians may prescribe medications in combination, sequential, or rotational therapeutic regimens. This treatment strategy has the potential to improve the overall efficacy and safety of topical therapy; however, the effectiveness of this method may be compromised because the complexity of the therapeutic regimen may decrease patient compliance. Newer topical therapies that have a convenient once-daily dosing schedule are needed and will have important implications for patient compliance.

The effects of adaptive working memory training and mindfulness meditation training on processing efficiency and worry in high worriers.

PubMed

Course-Choi, Jenna; Saville, Harry; Derakshan, Nazanin

2017-02-01

Worry is the principle characteristic of generalised anxiety disorder, and has been linked to deficient attentional control, a main function of working memory (WM). Adaptive WM training and mindfulness meditation practice (MMP) have both shown potential to increase attentional control. The present study hence investigates the individual and combined effects of MMP and a dual adaptive n-back task on a non-clinical, randomised sample of high worriers. 60 participants were tested before and after seven days of training. Assessment included self-report questionnaires, as well as performance tasks measuring attentional control and working memory capacity. Combined training resulted in continued reduction in worry in the week after training, highlighting the potential of utilising n-back training as an adjunct to established clinical treatment. Engagement with WM training correlated with immediate improvements in attentional control and resilience, with worry decreasing over time. Implications of these findings and suggestions for future research are discussed. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Dependence and caring in clinical communication: the relevance of attachment and other theories.

PubMed

Salmon, Peter; Young, Bridget

2009-03-01

Clinical relationships are usually asymmetric, being defined by patients' dependence and practitioners' care. Our aims are to: (i) identify literature that can contribute to theory for researching and teaching clinical communication from this perspective; (ii) highlight where theoretical development is needed; and (iii) test the utility of the emerging theory by identifying whether it leads to implications for educational practice. Selective and critical review of research concerned with dependence and caring in clinical and non-clinical relationships. Attachment theory helps to understand patients' need to seek safety in relationships with expert and authoritative practitioners but is of limited help in understanding practitioners' caring. Different theories that formulate practitioners' care as altruistic, rewarded by personal connection or as a contract indicate the potential importance of practitioners' emotions, values and sense of role in understanding their clinical communication. Extending the theoretical grounding of clinical communication can accommodate patients' dependence and practitioners' caring without return to medical paternalism. A broader theoretical base will help educators to address the inherent subjectivity of clinical relationships, and researchers to distinguish scientific questions about how patients and clinicians are from normative questions about how they should be.

Pathophysiological Mechanisms of Chronic Venous Disease and Implications for Venoactive Drug Therapy.

PubMed

Mansilha, Armando; Sousa, Joel

2018-06-05

Chronic venous disease (CVD) is a common pathology, with significant physical and psychological impacts for patients and high economic costs for national healthcare systems. Throughout the last decades, several risk factors for this condition have been identified, but only recently, have the roles of inflammation and endothelial dysfunction been properly assessed. Although still incompletely understood, current knowledge of the pathophysiological mechanisms of CVD reveals several potential targets and strategies for therapeutic intervention, some of which are addressable by currently available venoactive drugs. The roles of these drugs in the clinical improvement of venous tone and contractility, reduction of edema and inflammation, as well as in improved microcirculation and venous ulcer healing have been studied extensively, with favorable results reported in the literature. Here, we aim to review these pathophysiological mechanisms and their implications regarding currently available venoactive drug therapies.

Social (Pragmatic) Communication Disorder and Its Relation to the Autism Spectrum: Dilemmas Arising From the DSM-5 Classification.

PubMed

Brukner-Wertman, Yael; Laor, Nathaniel; Golan, Ofer

2016-08-01

DSM-5 introduced two diagnoses describing neurodevelopmental deficits in social communication (SC); Autism Spectrum Disorder (ASD) and Social (Pragmatic) Communication Disorder (SPCD). These diagnoses are differentiated by Repetitive and Restricted Behaviors (RRB), required for an ASD diagnosis and absent in SPCD. We highlight the gaps between the research into SPCD and DSM-5's diagnostic criteria, and discuss the clinical implications of this diagnostic decision. We argue that DSM-5's demand for full manifestation of both SC and RRB axes when diagnosing ASD, prematurely forced a categorical view on the continual nature of the potentially dependent SC and RRB phenotypes. We conclude by highlighting the implications of this differential diagnostic decision on public health policies, designated therapy, and the need for further research regarding SPCD.

Antifungal susceptibility of 175 Aspergillus isolates from various clinical and environmental sources.

PubMed

Sabino, Raquel; Carolino, Elisabete; Veríssimo, Cristina; Martinez, Marife; Clemons, Karl V; Stevens, David A

2016-10-01

Some environmental Aspergillus spp. isolates have been described as resistant to antifungals, potentially causing an emerging medical problem. In the present work, the antifungal susceptibility profile of 41 clinical and 134 environmental isolates of Aspergillus was determined using the CLSI microdilution method. The aim of this study was to compare environmental and clinical isolates with respect to their susceptibility, and assess the potential implications for therapy of isolates encountered in different environments. To our knowledge, this is the first report comparing antifungal susceptibility profiles of Aspergillus collected from different environmental sources (poultries, swineries, beach sand, and hospital environment). Significant differences were found in the distribution of the different species sections for the different sources. Significant differences were also found in the susceptibility profile of the different Aspergillus sections recovered from the various sources. Clear differences were found between the susceptibility of clinical and environmental isolates for caspofungin, amphotericin B and posaconazole, with clinical isolates showing overall greater susceptibility, except for caspofungin. In comparison to clinical isolates, hospital environmental isolates showed significantly less susceptibility to amphotericin B and posaconazole. These data indicate that species section identity and the site from which the isolate was recovered influence the antifungal susceptibility profile, which may affect initial antifungal choices. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Religion, assessment and the problem of 'normative uncertainty' for mental health student nurses: a critical incident-informed qualitative interview study.

PubMed

Bassett, A M; Baker, C; Cross, S

2015-10-01

There is limited research around how mental health (MH) student nurses interpret and differentiate between people's religious and cultural beliefs and the existence of psychopathological symptomatology and experiences. Here we focus on one cultural issue that arose from research exploring how MH student nurses approach and interpret religion and culture in their practice - that is, the difficulties in determining the clinical significance of the religious beliefs and experiences expressed by the people they care for. While problems with establishing the cultural boundaries of normality in clinical assessments are an important area of debate in cultural psychiatry, it remains a peripheral issue in MH nurse education. An anthropologically informed qualitative research design underpinned 'critical incident' (CI)-focused ethnographic interviews with 36 second and third-year MH nursing field students and seven undergraduate MH branch lecturers. Follow up focus groups were also carried out. Interview transcripts were subject to thematic analysis. Four subthemes were identified under the broad theme of the clinical significance of religious-type expression and experience: (1) identifying the difference between delusions and religious belief; (2) identifying whether an experience was hallucination or religious experience; (3) the clinical implications of such challenges; and (4) applying religion-specific knowledge. There are clinical implications that may result from the difficulties with assessing the clinical significance of religious beliefs and experiences, identified in both our research and within international cultural psychiatry literature and research. Misinterpretation and therefore wrongly assessing someone's experience as pathological is a significant concern. It is suggested that CI analysis could be adapted to help nurses, nursing students and nurse educators recognize the religious dimensions of mental distress, particularly those that then potentially impact upon the accuracy and person centeredness of clinical assessment. Further research is proposed to investigate the clinical assessment and training needs of nurses in the area of religion and mental distress. © 2015 John Wiley & Sons Ltd.

Location of core diagnostic information across various sequences in brain MRI and implications for efficiency of MRI scanner utilization.

PubMed

Sharma, Aseem; Chatterjee, Arindam; Goyal, Manu; Parsons, Matthew S; Bartel, Seth

2015-04-01

Targeting redundancy within MRI can improve its cost-effective utilization. We sought to quantify potential redundancy in our brain MRI protocols. In this retrospective review, we aggregated 207 consecutive adults who underwent brain MRI and reviewed their medical records to document clinical indication, core diagnostic information provided by MRI, and its clinical impact. Contributory imaging abnormalities constituted positive core diagnostic information whereas absence of imaging abnormalities constituted negative core diagnostic information. The senior author selected core sequences deemed sufficient for extraction of core diagnostic information. For validating core sequences selection, four readers assessed the relative ease of extracting core diagnostic information from the core sequences. Potential redundancy was calculated by comparing the average number of core sequences to the average number of sequences obtained. Scanning had been performed using 9.4±2.8 sequences over 37.3±12.3 minutes. Core diagnostic information was deemed extractable from 2.1±1.1 core sequences, with an assumed scanning time of 8.6±4.8 minutes, reflecting a potential redundancy of 74.5%±19.1%. Potential redundancy was least in scans obtained for treatment planning (14.9%±25.7%) and highest in scans obtained for follow-up of benign diseases (81.4%±12.6%). In 97.4% of cases, all four readers considered core diagnostic information to be either easily extractable from core sequences or the ease to be equivalent to that from the entire study. With only one MRI lacking clinical impact (0.48%), overutilization did not seem to contribute to potential redundancy. High potential redundancy that can be targeted for more efficient scanner utilization exists in brain MRI protocols.

Effect of security threats on primary care access in Logar province, Afghanistan.

PubMed

Morikawa, Masahiro J

2008-01-01

Security threats are a major concern for access to health care in many war-torn communities; however, there is little quantified data on actual access to care in rural communities during war. Kinderberg International e.V. provided primary care in rural Logar province, Afghanistan, for these three years in eight districts until they were integrated into the new health care structure led by the Ministry of Health in early 2005. We examined the number of patients visiting our clinic before and during the security threats related to the parliamentary election and subsequent national assembly in 2004. The number of patients declined in remote clinics while the number increased in central locations. This finding has an important practical implication: the monitoring of access to care should include remote clinics, otherwise it may potentially underestimate compromised access to health care due to security threats.

The gut microbiota and the liver: implications for clinical practice.

PubMed

Quigley, Eamonn M; Monsour, Howard P

2013-11-01

While a central role for the microbiota in the precipitation of infectious and non-infectious complications of liver disease has been long established, evidence for a more fundamental role in the etiology of several liver diseases continues to accumulate. However, though progress is rapidly occurring in this area, the definitive delineation of the precise relevance of changes in the microbiota to various forms and stages of liver disease is still far from complete. While high quality clinical evidence supports the use of antibiotic therapy, in the management of hepatic encephalopathy, spontaneous bacterial peritonitis and other infectious complications, how these interventions impact on the microbiota and microbiota-host interactions has not been clearly defined. Although probiotics and even, perhaps, fecal transplantation hold promise in the management of liver disease, and the potential impact of probiotics is supported by a considerable amount of laboratory data, high-quality clinical evidence is scanty.

"A golden opportunity": Exploring interprofessional learning and practice in rural clinical settings.

PubMed

Spencer, Judy; Woodroffe, Jessica; Cross, Merylin; Allen, Penny

2015-01-01

Little is known about interprofessional practice (IPP) and interprofessional learning (IPL) in rural health services, despite national funding and continuing emphasis on increasing students' clinical placements in rural areas. This short paper outlines a study in Tasmania, Australia, which investigated how and under what contexts and conditions IPP and IPL occur in rural clinical settings, and the enabling factors and strategies that promote this learning and practice. This study employed a mixed method design comprising focus group discussions and a survey involving health professionals from two rural health services. The findings demonstrate that formal and informal arrangements, the collaborative nature of small, close-knit healthcare teams and patient-centred models of care employed in rural practice settings, provide ideal contexts for IPP and IPL. The study has implications for promoting organisational readiness for IPP and IPL and harnessing the potential of rural services to promote and develop students' interprofessional capability.

Commercial landscape of noninvasive prenatal testing in the United States.

PubMed

Agarwal, Ashwin; Sayres, Lauren C; Cho, Mildred K; Cook-Deegan, Robert; Chandrasekharan, Subhashini

2013-06-01

Cell-free fetal DNA-based noninvasive prenatal testing (NIPT) could significantly change the paradigm of prenatal testing and screening. Intellectual property (IP) and commercialization promise to be important components of the emerging debate about clinical implementation of these technologies. We have assembled information about types of testing, prices, turnaround times, and reimbursement of recently launched commercial tests in the United States from the trade press, news articles, and scientific, legal, and business publications. We also describe the patenting and licensing landscape of technologies underlying these tests and ongoing patent litigation in the United States. Finally, we discuss how IP issues may affect clinical translation of NIPT and their potential implications for stakeholders. Fetal medicine professionals (clinicians and researchers), genetic counselors, insurers, regulators, test developers, and patients may be able to use this information to make informed decisions about clinical implementation of current and emerging noninvasive prenatal tests. © 2013 John Wiley & Sons, Ltd.

European League against rheumatism - selected presentation and poster a highlights June 11th to 13th 2013.

PubMed

Braddock, Martin

2014-02-01

The heterogeneous pathology of many autoimmune diseases warrants the continual discovery and development of new drugs. Drawing on selected oral presentations and selected poster displays, this article highlights some new developments in the pharmacological validation of molecular targets implicated in inflammatory autoimmune disease and may be of direct importance to scientists working in this field. This report describes the current state of the pharmacology of selected drugs and targets which may have utility in modulating immune function and autoimmune inflammatory disease. Many new molecules are progressing through clinical development for the treatment of rheumatological diseases. The value of the basic nonclinical and clinical research presented is to further pharmacological knowledge of the molecule, better understand the benefit-risk associated with clinical development and to assist in supporting the potential position of a new drug in the current treatment paradigm.

Corticostriatal circuitry in regulating diseases characterized by intrusive thinking

PubMed Central

Kalivas, Benjamin C.; Kalivas, Peter W.

2016-01-01

Intrusive thinking triggers clinical symptoms in many neuropsychiatric disorders. Using drug addiction as an exemplar disorder sustained in part by intrusive thinking, we explore studies demonstrating that impairments in corticostriatal circuitry strongly contribute to intrusive thinking. Neuroimaging studies have long implicated this projection in cue-induced craving to use drugs, and preclinical models show that marked changes are produced at corticostriatal synapses in the nucleus accumbens during a relapse episode. We delineate an accumbens microcircuit that mediates cue-induced drug seeking becoming an intrusive event. This microcircuit harbors many potential therapeutic targets. We focus on preclinical and clinical studies, showing that administering N-acetylcysteine restores uptake of synaptic glutamate by astroglial glutamate transporters and thereby inhibits intrusive thinking. We posit that because intrusive thinking is a shared endophenotype in many disorders, N-acetylcysteine has positive effects in clinical trials for a variety of neuropsychiatric disorders, including drug addiction, gambling, trichotillomania, and depression. PMID:27069381

Immunomodulatory effect of morphine: therapeutic implications.

PubMed

Dinda, Amit; Gitman, Michael; Singhal, Pravin C

2005-07-01

The immunosuppressive as well as modulatory effects of morphine have been known in clinical medicine for > 100 years. Recent developments in molecular immunology, including experiments in mu (mu) opioid receptor knockout mice has led to a better understanding of central and peripheral mechanisms involved in this process. Though there is a large volume of literature documenting adverse effects of immunosupression following the use of morphine, several reports confirm its potential usefulness as an immunomodulator. In vitro and in vivo animal experiments have demonstrated wide-spectrum effects of morphine, including anti-inflammatory, antifibrotic, antitumour, cardioprotective and renoprotective. Immunomodulation is an important field in modern medicine with rapid advancement in recent years. Though a final statement regarding the clinical relevance of morphine-induced immunomodulation cannot be made at this juncture, nevertheless, it is worthwhile to review current developments. It may encourage further clinical studies to elucidate the influence of morphine treatment on immune regulation in different specialties of medicine.

Corticostriatal circuitry in regulating diseases characterized by intrusive thinking.

PubMed

Kalivas, Benjamin C; Kalivas, Peter W

2016-03-01

Intrusive thinking triggers clinical symptoms in many neuropsychiatric disorders. Using drug addiction as an exemplar disorder sustained in part by intrusive thinking, we explore studies demonstrating that impairments in corticostriatal circuitry strongly contribute to intrusive thinking. Neuroimaging studies have long implicated this projection in cue-induced craving to use drugs, and preclinical models show that marked changes are produced at corticostriatal synapses in the nucleus accumbens during a relapse episode. We delineate an accumbens microcircuit that mediates cue-induced drug seeking becoming an intrusive event. This microcircuit harbors many potential therapeutic targets. We focus on preclinical and clinical studies, showing that administering N-acetylcysteine restores uptake of synaptic glutamate by astroglial glutamate transporters and thereby inhibits intrusive thinking. We posit that because intrusive thinking is a shared endophenotype in many disorders, N-acetylcysteine has positive effects in clinical trials for a variety of neuropsychiatric disorders, including drug addiction, gambling, trichotillomania, and depression.

Genetic modification of hematopoietic stem cells: recent advances in the gene therapy of inherited diseases.

PubMed

Bueren, Juan A; Guenechea, Guillermo; Casado, José A; Lamana, María Luisa; Segovia, José C

2003-01-01

Hematopoietic stem cells constitute a rare population of precursor cells with remarkable properties for being used as targets in gene therapy protocols. The last years have been particularly productive both in the fields of gene therapy and stem cell biology. Results from ongoing clinical trials have shown the first unquestionable clinical benefits of immunodeficient patients transplanted with genetically modified autologous stem cells. On the other hand, severe side effects in a few patients treated with gene therapy have also been reported, indicating the usefulness of further improving the vectors currently used in gene therapy clinical trials. In the field of stem cell biology, evidence showing the plastic potential of adult hematopoietic stem cells and data indicating the multipotency of adult mesenchymal precursor cells have been presented. Also, the generation of embryonic stem cells by means of nuclear transfer techniques has appeared as a new methodology with direct implications in gene therapy.

Natural products as modulator of autophagy with potential clinical prospects.

PubMed

Wang, Peiqi; Zhu, Lingjuan; Sun, Dejuan; Gan, Feihong; Gao, Suyu; Yin, Yuanyuan; Chen, Lixia

2017-03-01

Natural compounds derived from living organisms are well defined for their remarkable biological and pharmacological properties likely to be translated into clinical use. Therefore, delving into the mechanisms by which natural compounds protect against diverse diseases may be of great therapeutic benefits for medical practice. Autophagy, an intricate lysosome-dependent digestion process, with implications in a wide variety of pathophysiological settings, has attracted extensive attention over the past few decades. Hitherto, accumulating evidence has revealed that a large number of natural products are involved in autophagy modulation, either inducing or inhibiting autophagy, through multiple signaling pathways and transcriptional regulators. In this review, we summarize natural compounds regulating autophagy in multifarious diseases including cancer, neurodegenerative diseases, cardiovascular diseases, metabolic diseases, and immune diseases, hoping to inspire further investigation of the underlying mechanisms of natural compounds and to facilitate their clinical use for multiple human diseases.

CSF-1R Inhibitor Development: Current Clinical Status.

PubMed

Peyraud, Florent; Cousin, Sophie; Italiano, Antoine

2017-09-05

Colony-stimulating factor 1 receptor (CSF-1R) and its ligands, CSF-1 and interleukin 34 (IL-34), regulate the function and survival of tumor-associated macrophages, which are involved in tumorigenesis and in the suppression of antitumor immunity. Moreover, the CSF-1R/CSF-1 axis has been implicated in the pathogenesis of pigmented villonodular synovitis (PVNS), a benign tumor of the synovium. As advanced or metastatic malignant solid tumors and relapsed/refractory PVNS remain unresolved therapeutic problems, new approaches are needed to improve the outcome of patients with these conditions. In solid tumors, targeting CSF-1R via either small molecules or antibodies has shown interesting results in vitro but limited antitumor activity in vivo. Concerning PVNS, clinical trials assessing CSF-1R inhibitors have revealed promising initial outcomes. Blocking CSF-1/CSF-1R signaling represents a promising immunotherapy approach and several new potential combination therapies for future clinical testing.

Force-dependent breaching of the basement membrane.

PubMed

Chang, Tammy T; Thakar, Dhruv; Weaver, Valerie M

2017-01-01

Clinically, non-invasive carcinomas are confined to the epithelial side of the basement membrane and are classified as benign, whereas invasive cancers invade through the basement membrane and thereby acquire the potential to metastasize. Recent findings suggest that, in addition to protease-mediated degradation and chemotaxis-stimulated migration, basement membrane invasion by malignant cells is significantly influenced by the stiffness of the associated interstitial extracellular matrix and the contractility of the tumor cells that is dictated in part by their oncogenic genotype. In this review, we highlight recent findings that illustrate unifying molecular mechanisms whereby these physical cues contribute to tissue fibrosis and malignancy in three epithelial organs: breast, pancreas, and liver. We also discuss the clinical implications of these findings and the biological properties and clinical challenges linked to the unique biology of each of these organs. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Professional boundaries in the era of the Internet.

PubMed

Gabbard, Glen O; Kassaw, Kristin A; Perez-Garcia, Gonzalo

2011-01-01

The era of the Internet presents new dilemmas in educating psychiatrists about professional boundaries. The objective of this overview is to clarify those dilemmas and offer recommendations for dealing with them. The characteristics of social networking sites, blogs, and search engines are reviewed with a specific focus on their potential to present problems of professional boundaries for psychiatrists. The professional boundary questions that have arisen in the expanded world of online communication can be subdivided into three areas: ethical concerns, professionalism issues, and clinical dilemmas. Only the first category involves true boundary problems as normally defined. The expansion of the Internet has redefined traditional areas of privacy and anonymity in the clinical setting. Guidelines are proposed to manage the alteration of professional boundaries, as well as issues of professionalism and clinical work, that have arisen from the complexities of cyberspace. The author discusses implications for residency training.

Doctors and Vampires in Sub-Saharan Africa: Ethical Challenges in Clinical Trial Research

PubMed Central

Peeters Grietens, Koen; Ribera, Joan Muela; Erhart, Annette; Hoibak, Sarah; Ravinetto, Raffaella M.; Gryseels, Charlotte; Dierickx, Susan; O'Neill, Sarah; Muela, Susanna Hausmann; D'Alessandro, Umberto

2014-01-01

Collecting blood samples from individuals recruited into clinical research projects in sub-Saharan Africa can be challenging. Strikingly, one of the reasons for participant reticence is the occurrence of local rumors surrounding “blood stealing” or “blood selling.” Such fears can potentially have dire effects on the success of research projects—for example, high dropout rates that would invalidate the trial's results—and have ethical implications related to cultural sensitivity and informed consent. Though commonly considered as a manifestation of the local population's ignorance, these rumors represent a social diagnosis and a logical attempt to make sense of sickness and health. Born from historical antecedents, they reflect implicit contemporary structural inequalities and the social distance between communities and public health institutions. We aim at illustrating the underlying logic governing patients' fear and argue that the management of these beliefs should become an intrinsic component of clinical research. PMID:24821846

Commercial Landscape of noninvasive prenatal testing in the United States

PubMed Central

Agarwal, Ashwin; Sayres, Lauren C.; Cho, Mildred K.; Cook-Deegan, Robert; Chandrasekharan, Subhashini

2014-01-01

Cell-free fetal DNA-based noninvasive prenatal testing (NIPT) could significantly change the paradigm of prenatal testing and screening. Intellectual property (IP) and commercialization promise to be important components of the emerging debate about clinical implementation of these technologies. We have assembled information about types of testing, prices, turnaround times and reimbursement of recently launched commercial tests in the United States from the trade press, news articles, and scientific, legal, and business publications. We also describe the patenting and licensing landscape of technologies underlying these tests and ongoing patent litigation in the United States. Finally, we discuss how IP issues may affect clinical translation of NIPT and their potential implications for stakeholders. Fetal medicine professionals (clinicians and researchers), genetic counselors, insurers, regulators, test developers and patients may be able to use this information to make informed decisions about clinical implementation of current and emerging noninvasive prenatal tests. PMID:23686656

Single-cell proteomics: potential implications for cancer diagnostics.

PubMed

Gavasso, Sonia; Gullaksen, Stein-Erik; Skavland, Jørn; Gjertsen, Bjørn T

2016-01-01

Single-cell proteomics in cancer is evolving and promises to provide more accurate diagnoses based on detailed molecular features of cells within tumors. This review focuses on technologies that allow for collection of complex data from single cells, but also highlights methods that are adaptable to routine cancer diagnostics. Current diagnostics rely on histopathological analysis, complemented by mutational detection and clinical imaging. Though crucial, the information gained is often not directly transferable to defined therapeutic strategies, and predicting therapy response in a patient is difficult. In cancer, cellular states revealed through perturbed intracellular signaling pathways can identify functional mutations recurrent in cancer subsets. Single-cell proteomics remains to be validated in clinical trials where serial samples before and during treatment can reveal excessive clonal evolution and therapy failure; its use in clinical trials is anticipated to ignite a diagnostic revolution that will better align diagnostics with the current biological understanding of cancer.

Shared decision-making – transferring research into practice: the Analytic Hierarchy Process (AHP)

PubMed Central

Dolan, James G.

2008-01-01

Objective To illustrate how the Analytic Hierarchy Process (AHP) can be used to promote shared decision-making and enhance clinician-patient communication. Methods Tutorial review. Results The AHP promotes shared decision making by creating a framework that is used to define the decision, summarize the information available, prioritize information needs, elicit preferences and values, and foster meaningful communication among decision stakeholders. Conclusions The AHP and related multi-criteria methods have the potential for improving the quality of clinical decisions and overcoming current barriers to implementing shared decision making in busy clinical settings. Further research is needed to determine the best way to implement these tools and to determine their effectiveness. Practice Implications Many clinical decisions involve preference-based trade-offs between competing risks and benefits. The AHP is a well-developed method that provides a practical approach for improving patient-provider communication, clinical decision-making, and the quality of patient care in these situations. PMID:18760559

Mental representations of attachment in eating disorders: a pilot study using the Adult Attachment Interview.

PubMed

Barone, Lavinia; Guiducci, Valentina

2009-07-01

Mental representations of attachment in a sample of adults with Eating Disorders (ED) were assessed using the Adult Attachment Interview (AAI). Sixty subjects participated in the study: 30 non-clinical and 30 clinical. The results obtained showed a specific distribution of attachment patterns in the clinical sample: 10% Free/Autonomous (F), 47% Insecure-Dismissing (Ds), 17% Insecure-Entangled/Preoccupied (E) and about 26% disorganized (CC/U). The two samples differed in their attachment pattern distribution and were significantly different on some coding system scales. Further information was obtained by analyzing differences between the three ED subtypes considered (i.e. Anorexia Nervosa, Bulimia Nervosa and Binge Eating Disorder) and by investigating the differential role of the two parental figures in the definition of attachment representations. Results showed potential benefits in using the AAI coding system scales in addition to the main classifications in order to understand better the developmental issues involved in these disorders. Implications for developmental research and clinical nosology are discussed.

Cost-effectiveness analysis of unsafe abortion and alternative first-trimester pregnancy termination strategies in Nigeria and Ghana.

PubMed

Hu, Delphine; Grossman, Daniel; Levin, Carol; Blanchard, Kelly; Adanu, Richard; Goldie, Sue J

2010-06-01

To explore the policy implications of increasing access to safe abortion in Nigeria and Ghana, we developed a computer-based decision analytic model which simulates induced abortion and its potential complications in a cohort of women, and comparatively assessed the cost-effectiveness of unsafe abortion and three first-trimester abortion modalities: hospital-based dilatation and curettage, hospital- and clinic-based manual vacuum aspiration (MVA), and medical abortion using misoprostol (MA). Assuming all modalities are equally available, clinic-based MVA is the most cost-effective option in Nigeria. If clinic-based MVA is not available, MA is the next best strategy. Conversely, in Ghana, MA is the most cost-effective strategy, followed by clinic-based MVA if MA is not available. From a real world policy perspective, increasing access to safe abortion in favor over unsafe abortion is the single most important factor in saving lives and societal costs, and is more influential than the actual choice of safe abortion modality.

Discovery, development, and clinical application of sugammadex sodium, a selective relaxant binding agent

PubMed Central

Welliver, Mark; McDonough, John; Kalynych, Nicholas; Redfern, Robert

2008-01-01

Neuromuscular blockade, induced by neuromuscular blocking agents, has allowed prescribed immobility, improved surgical exposure, optimal airway management conditions, and facilitated mechanical ventilation. However, termination of the effects of neuromuscular blocking agents has, until now, remained limited. A novel cyclodextrin encapsulation process offers improved termination of the paralytic effects of aminosteroidal non-depolarizing neuromuscular blocking agents. Sugammadex sodium is the first in a new class of drug called selective relaxant binding agents. Currently, in clinical trials, sugammadex, a modified gamma cyclodextrin, has shown consistent and rapid termination of neuromuscular blockade with few side effects. The pharmacology of cyclodextrins in general and sugammadex in particular, together with the results of current clinical research are reviewed. The ability of sugammadex to terminate the action of neuromuscular blocking agents by direct encapsulation is compared to the indirect competitive antagonism of their effects by cholinesterase inhibitors. Also discussed are the clinical implications that extend beyond fast, effective reversal, including numerous potential perioperative benefits. PMID:19920893

Mobile health: the power of wearables, sensors, and apps to transform clinical trials.

PubMed

Munos, Bernard; Baker, Pamela C; Bot, Brian M; Crouthamel, Michelle; de Vries, Glen; Ferguson, Ian; Hixson, John D; Malek, Linda A; Mastrototaro, John J; Misra, Veena; Ozcan, Aydogan; Sacks, Leonard; Wang, Pei

2016-07-01

Mobile technology has become a ubiquitous part of everyday life, and the practical utility of mobile devices for improving human health is only now being realized. Wireless medical sensors, or mobile biosensors, are one such technology that is allowing the accumulation of real-time biometric data that may hold valuable clues for treating even some of the most devastating human diseases. From wearable gadgets to sophisticated implantable medical devices, the information retrieved from mobile technology has the potential to revolutionize how clinical research is conducted and how disease therapies are delivered in the coming years. Encompassing the fields of science and engineering, analytics, health care, business, and government, this report explores the promise that wearable biosensors, along with integrated mobile apps, hold for improving the quality of patient care and clinical outcomes. The discussion focuses on groundbreaking device innovation, data optimization and validation, commercial platform integration, clinical implementation and regulation, and the broad societal implications of using mobile health technologies. © 2016 New York Academy of Sciences.

Nursing and health-care assistant experience of supervision in a medium secure psychiatric service for women: implications for service development.

PubMed

Long, C G; Harding, S; Payne, K; Collins, L

2014-03-01

In secure psychiatric services where the potential for 'burnout' by nurses is high, clinical supervision is viewed as a key to reflective practice to support staff in stressful working environments. Barriers to the uptake of clinical supervision in such service settings are personal and organizational. The study was prompted by the need to evaluate the effectiveness of supervision for registered nurses and health-care assistants (HCAs) and a desire to use survey findings to improve the quality and uptake of supervision. The study examined the perceived benefits, the best practice elements and the practical aspects of clinical supervision including how to improve practice. An approximate uptake of clinical supervision by 50% of staff confirmed previous findings; that HCAs were significantly less likely to engage in supervision and less likely to perceive benefit from it. Initiatives to address the training and managerial obstacles to the provision of formal supervision are described. © 2013 John Wiley & Sons Ltd.

Using the Situated Clinical Decision-Making framework to guide analysis of nurses' clinical decision-making.

PubMed

Gillespie, Mary

2010-11-01

Nurses' clinical decision-making is a complex process that holds potential to influence the quality of care provided and patient outcomes. The evolution of nurses' decision-making that occurs with experience has been well documented. In addition, literature includes numerous strategies and approaches purported to support development of nurses' clinical decision-making. There has been, however, significantly less attention given to the process of assessing nurses' clinical decision-making and novice clinical educators are often challenged with knowing how to best support nurses and nursing students in developing their clinical decision-making capacity. The Situated Clinical Decision-Making framework is presented for use by clinical educators: it provides a structured approach to analyzing nursing students' and novice nurses' decision-making in clinical nursing practice, assists educators in identifying specific issues within nurses' clinical decision-making, and guides selection of relevant strategies to support development of clinical decision-making. A series of questions is offered as a guide for clinical educators when assessing nurses' clinical decision-making. The discussion presents key considerations related to analysis of various decision-making components, including common sources of challenge and errors that may occur within nurses' clinical decision-making. An exemplar illustrates use of the framework and guiding questions. Implications of this approach for selection of strategies that support development of clinical decision-making are highlighted. Copyright © 2010 Elsevier Ltd. All rights reserved.

[Radiation-induced bystander effect: the important part of ionizing radiation response. Potential clinical implications].

PubMed

Wideł, Maria; Przybyszewski, Waldemar; Rzeszowska-Wolny, Joanna

2009-08-18

It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the "bystander effect" or "radiation-induced bystander effect" (RIBE). This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy), but also after conventional irradiation (X-rays, gamma rays) at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not definitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effect may have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation field and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The bystander effect may be a potentially harmful or a useful event in radiotherapy. The elevation of damage to tumor cells not directly hit by radiation or the initiation of tumor cell differentiation may increase the therapeutic ratio. If, however, molecular species secreted by irradiated tumor cells in vivo damage neighboring normal cells (epithelial and endothelial cells, fibroblasts, or lymphocytes), the bystander effect would be harmful and could lead to increased side effects in normal tissue. This is especially important in modern radiotherapy, as 3D conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) are aimed at diminishing the radiation dose in normal tissues. Recent in vivo studies on animals indicate that bystander effects may appear in organs and tissues remote from the irradiated field and the extension of tissue damage seems to be tissue-type dependent. However, recent experimental results indicate that non-irradiated cells that are neighbors of irradiated cells may diminish radiation damage in the radiation-focused cells. Less is known about the bystander effect during fractionated irradiation. Thus the clinical implications of the bystander effect and its possible modification for radiotherapeutic usefulness is still under debate.

Translational Implications of Tumor Heterogeneity

PubMed Central

Jamal-Hanjani, Mariam; Quezada, Sergio A.; Larkin, James; Swanton, Charles

2015-01-01

Advances in next-generation sequencing and bioinformatics have led to an unprecedented view of the cancer genome and its evolution. Genomic studies have demonstrated the complex and heterogeneous clonal landscape of tumors of different origins, and the potential impact of intratumor heterogeneity on treatment response and resistance, cancer progression and the risk of disease relapse. However, the significance of subclonal mutations, in particular mutations in driver genes, and their evolution through time and their dynamics in response to cancer therapies, is yet to be determined. The necessary tools are now available to prospectively determine whether clonal heterogeneity can be used as a biomarker of clinical outcome, and to what extent subclonal somatic alterations might influence clinical outcome. Studies that employ longitudinal tissue sampling, integrating both genomic and clinical data, have the potential to reveal the subclonal composition and track the evolution of tumors in order to address these questions, and to begin to define the breadth of genetic diversity in different tumor types, and its relevance to patient outcome. Such studies may provide further evidence for novel drug resistance mechanisms informing novel combinatorial, adaptive and tumour immune-therapies placed within the context of tumor evolution. PMID:25770293

Consensus paper on the "executive summary of the international conference on Mediterranean diet and health: a lifelong approach" an Italian initiative supported by the Mediterranean Diet Foundation and the Menarini Foundation.

PubMed

Boccardi, Virginia; Calvani, Riccardo; Limongi, Federica; Marseglia, Anna; Mason, Alexandra; Noale, Marianna; Rogoli, Domenico; Veronese, Nicola; Crepaldi, Gaetano; Maggi, Stefania

The Mediterranean Diet Foundation, in collaboration with the International Menarini Foundation, organized the "International Conference on Mediterranean Diet and Health: A Lifelong Approach." The Conference was held in Ostuni (Puglia, Italy) from March 30 to April 1, 2017. The event received the endorsement of the American Federation for Aging Research, the Research Consortium "Luigi Amaducci," the European Nutrition for Health Alliance, the European Union Geriatric Medicine Society, the Clinical Section of the International Association of Gerontology and Geriatrics-European Region, the National Research Council Research Project on Aging, the Italian Society of Gerontology and Geriatrics, and the Italian Society of Clinical Nutrition and Metabolism. During the conference, results were presented from major studies on dietary interventions aiming to assess the efficacy of the Mediterranean diet in the prevention of chronic diseases and the potential underlying mechanisms. Twenty-six international speakers, in seven different sessions, discussed the biological basis, clinical impact, health policy, and behavioral implications of the Mediterranean diet, and its use in potential interventions for health promotion. Copyright © 2018 Elsevier Inc. All rights reserved.

Impact of product-related factors on immunogenicity of biotherapeutics.

PubMed

Singh, Satish Kumar

2011-02-01

All protein therapeutics have the potential to be immunogenic. Several factors, including patient characteristics, disease state, and the therapy itself, influence the generation of an immune response. Product-related factors such as the molecule design, the expression system, post-translational modifications, impurities, contaminants, formulation and excipients, container, closure, as well as degradation products are all implicated. However, a critical examination of the available data shows that clear unequivocal evidence for the impact of these latter factors on clinical immunogenicity is lacking. No report could be found that clearly deconvolutes the clinical impact of the product attributes on patient susceptibility. Aggregation carries the greatest concern as a risk factor for immunogenicity, but the impact of aggregates is likely to depend on their structure as well as on the functionality (e.g., immunostimulatory or immunomodulatory) of the therapeutic. Preclinical studies are not yet capable of assessing the clinically relevant immunogenicity potential of these product-related factors. Simply addressing these risk factors as part of product development will not eliminate immunogenicity. Minimization of immunogenicity has to begin at the molecule design stage by reducing or eliminating antigenic epitopes and building in favorable physical and chemical properties. Copyright © 2010 Wiley-Liss, Inc.

Glutamate-Modulating Drugs as a Potential Therapeutic Strategy in Obsessive-Compulsive Disorder

PubMed Central

Marinova, Zoya; Chuang, De-Maw; Fineberg, Naomi

2017-01-01

Objective: Abstract: Obsessive-compulsive disorder (OCD) is a mental disease commonly associated with severe distress and impairment of social functioning. Serotonin reuptake inhibitors and/or cognitive behavioural therapy are the therapy of choice, however up to 40% of patients do not respond to treatment. Glutamatergic signalling has also been implicated in OCD. The aim of the current study was to review the clinical evidence for therapeutic utility of glutamate-modulating drugs as an augmentation or monotherapy in OCD patients. Methods: We conducted a search of the MEDLINE database for clinical studies evaluating the effect of glutamate-modulating drugs in OCD. Results: Memantine is the compound most consistently showing a positive effect as an augmentation therapy in OCD. Anti-convulsant drugs (lamotrigine, topiramate) and riluzole may also provide therapeutic benefit to some OCD patients. Finally, ketamine may be of interest due to its potential for a rapid onset of action. Conclusion: Further randomized placebo-controlled trials in larger study populations are necessary in order to draw definitive conclusions on the utility of glutamate-modulating drugs in OCD. Furthermore, genetic and epigenetic factors, clinical symptoms and subtypes predicting treatment response to glutamate-modulating drugs need to be investigated systematically. PMID:28322166

Precision medicine for advanced prostate cancer

PubMed Central

Mullane, Stephanie A.; Van Allen, Eliezer M.

2016-01-01

Purpose of review Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Recent findings Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Summary Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients. PMID:26909474

Precision medicine for advanced prostate cancer.

PubMed

Mullane, Stephanie A; Van Allen, Eliezer M

2016-05-01

Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients.

Intraoperative Floppy Iris Syndrome: Pathophysiology, Prevention, and Treatment

PubMed Central

Flach, Allan J.

2009-01-01

Purpose: To extend upon previous reports, observations, and discussions of intraoperative floppy iris syndrome (IFIS) with the goal of providing new insight into the syndrome’s pathophysiology, prevention, and treatment. Methods: Following a review of IFIS and its relationship to autonomic pharmacology, evidence for anatomic changes following exposure of humans and other animals to autonomic drugs is described. The clinical implications for these findings are discussed as they relate to the treatment and prevention of this syndrome. Results: IFIS has been associated with the use of adrenergic antagonists even after they have been discontinued years prior to surgery. Some investigators believe that this persistence of IFIS reflects anatomic structural change. Evidence from laboratory experiments and human clinical studies using topically applied and systemic autonomic drugs supports the possibility of anatomic changes coexisting with IFIS observed during cataract surgery. Conclusions: IFIS is a relatively rare syndrome, often associated with the use of systemic α-blockers and conditions that influence dilator muscle tone. Laboratory and clinical evidence supports the possibility of anatomic changes following the use of autonomic drugs. The persistence of IFIS years after cessation of treatment with α-blockers suggests that the potential risks of discontinuing these drugs prior to cataract surgery outweigh potential benefits. PMID:20126500

Clinical Relevance of Prognostic and Predictive Molecular Markers in Gliomas.

PubMed

Siegal, Tali

2016-01-01

Sorting and grading of glial tumors by the WHO classification provide clinicians with guidance as to the predicted course of the disease and choice of treatment. Nonetheless, histologically identical tumors may have very different outcome and response to treatment. Molecular markers that carry both diagnostic and prognostic information add useful tools to traditional classification by redefining tumor subtypes within each WHO category. Therefore, molecular markers have become an integral part of tumor assessment in modern neuro-oncology and biomarker status now guides clinical decisions in some subtypes of gliomas. The routine assessment of IDH status improves histological diagnostic accuracy by differentiating diffuse glioma from reactive gliosis. It carries a favorable prognostic implication for all glial tumors and it is predictive for chemotherapeutic response in anaplastic oligodendrogliomas with codeletion of 1p/19q chromosomes. Glial tumors that contain chromosomal codeletion of 1p/19q are defined as tumors of oligodendroglial lineage and have favorable prognosis. MGMT promoter methylation is a favorable prognostic marker in astrocytic high-grade gliomas and it is predictive for chemotherapeutic response in anaplastic gliomas with wild-type IDH1/2 and in glioblastoma of the elderly. The clinical implication of other molecular markers of gliomas like mutations of EGFR and ATRX genes and BRAF fusion or point mutation is highlighted. The potential of molecular biomarker-based classification to guide future therapeutic approach is discussed and accentuated.

Anticoagulants in ischemia-guided management of non-ST-elevation acute coronary syndromes.

PubMed

Mayer, Martin

2017-03-01

The most recent joint guidelines from the American Heart Association (AHA) and American College of Cardiology (ACC) on the management of non-ST-elevation acute coronary syndromes (NSTE-ACS) are a result of a substantial and considered undertaking, and those involved deserve much recognition for their efforts. However, the handling of anticoagulants seems somewhat inadequate, and this is a highly-relevant matter when managing NSTE-ACS. Among areas of potential uncertainty, emergency medicine professionals might still be left wondering about the particulars of anticoagulant therapy when pursuing ischemia-guided management of NSTE-ACS (that is, managing NSTE-ACS without an intent for early invasive measures, such as coronary angiography and revascularization). This review seeks to provide insight into this question. Relevant clinical trials are appraised and translated into clinical context for emergency medicine professionals, including the implications of noteworthy advancements in the management of NSTE-ACS. Although current guidelines from the AHA and ACC suggest enoxaparin has better evidence than other anticoagulants in the setting of NSTE-ACS management, careful review of the evidence shows this is not actually clearly supported by the available evidence in the era of contemporary management. Unless and until better contemporary data emerge, emergency medicine professionals must carefully weigh the available evidence, its limitations, and the possible clinical implications of the various anticoagulant options when managing NSTE-ACS. Copyright © 2017 Elsevier Inc. All rights reserved.

TWEAK/Fn14 Axis-Targeted Therapeutics: Moving Basic Science Discoveries to the Clinic.

PubMed

Cheng, Emily; Armstrong, Cheryl L; Galisteo, Rebeca; Winkles, Jeffrey A

2013-12-23

The TNF superfamily member TWEAK (TNFSF12) is a multifunctional cytokine implicated in physiological tissue regeneration and wound repair. TWEAK is initially synthesized as a membrane-anchored protein, but furin cleavage within the stalk region can generate a secreted TWEAK isoform. Both TWEAK isoforms bind to a small cell surface receptor named Fn14 (TNFRSF12A) and this interaction stimulates various cellular responses, including proliferation and migration. Fn14, like other members of the TNF receptor superfamily, is not a ligand-activated protein kinase. Instead, TWEAK:Fn14 engagement promotes Fn14 association with members of the TNFR associated factor family of adapter proteins, which triggers activation of various signaling pathways, including the classical and alternative NF-κB pathways. Numerous studies have revealed that Fn14 gene expression is significantly elevated in injured tissues and in most solid tumor types. Also, sustained Fn14 signaling has been implicated in the pathogenesis of cerebral ischemia, chronic inflammatory diseases, and cancer. Accordingly, several groups are developing TWEAK- or Fn14-targeted agents for possible therapeutic use in patients. These agents include monoclonal antibodies, fusion proteins, and immunotoxins. In this article, we provide an overview of some of the TWEAK/Fn14 axis-targeted agents currently in pre-clinical animal studies or in human clinical trials and discuss two other potential approaches to target this intriguing signaling node.

Induction of P-glycoprotein expression and activity by Aconitum alkaloids: Implication for clinical drug–drug interactions

PubMed Central

Wu, Jinjun; Lin, Na; Li, Fangyuan; Zhang, Guiyu; He, Shugui; Zhu, Yuanfeng; Ou, Rilan; Li, Na; Liu, Shuqiang; Feng, Lizhi; Liu, Liang; Liu, Zhongqiu; Lu, Linlin

2016-01-01

The Aconitum species, which mainly contain bioactive Aconitum alkaloids, are frequently administered concomitantly with other herbal medicines or chemical drugs in clinics. The potential risk of drug–drug interactions (DDIs) arising from co-administration of Aconitum alkaloids and other drugs against specific targets such as P-glycoprotein (P-gp) must be evaluated. This study focused on the effects of three representative Aconitum alkaloids: aconitine (AC), benzoylaconine (BAC), and aconine, on the expression and activity of P-gp. We observed that Aconitum alkaloids increased P-gp expression in LS174T and Caco-2 cells in the order AC > BAC > aconine. Nuclear receptors were involved in the induction of P-gp. AC and BAC increased the P-gp transport activity. Strikingly, intracellular ATP levels and mitochondrial mass also increased. Furthermore, exposure to AC decreased the toxicity of vincristine and doxorubicin towards the cells. In vivo, AC significantly up-regulated the P-gp protein levels in the jejunum, ileum, and colon of FVB mice, and protected them against acute AC toxicity. Taken together, the findings of our in vitro and in vivo experiments indicate that AC can induce P-gp expression, and that co-administration of AC with P-gp substrate drugs may cause DDIs. Our findings have important implications for Aconitum therapy in clinics. PMID:27139035

The emerging role of histology in the choice of first-line treatment of advanced non-small cell lung cancer: implication in the clinical decision-making.

PubMed

Rossi, Antonio; Maione, Paolo; Bareschino, Maria Anna; Schettino, Clorinda; Sacco, Paola Claudia; Ferrara, Marianna Luciana; Castaldo, Vincenzo; Gridelli, Cesare

2010-01-01

Lung cancer is the leading cause of cancer mortality worldwide. Non-small cell lung cancer (NSCLC), accounting for about 85% of all lung cancers, includes squamous carcinoma, adenocarcinoma and undifferentiated large cell carcinoma. The majority of patients have advanced disease at diagnosis, and medical treatment is the cornerstone of management. Several randomized trials comparing third-generation platinum-based doublets concluded that all such combinations are comparable in their clinical efficacy, failing to document a difference based on histology. However, recent evidences, arising from the availability of pemetrexed, have shown that histology represents an important variable in the decision making. The major progresses in the understanding cancer biology and mechanism of oncogenesis have allowed the development of several potential molecular targets for cancer treatment such as vascular growth factor and its receptors and epidermal growth factor receptor. Targeted drugs seem to be safer or more effective in a specific histology subtype. All of these data have led to choose the optimal first-line treatment of advanced NSCLC based on histologic diagnosis. However, this scenario raises a diagnostic issue: a specific diagnosis of NSCLC histologic subtype is mandatory. This review will discuss these new evidences in the first-line treatment of advanced NSCLC and their implication in the current clinical decision-making.

Modelling the resource implications and budget impact of managing cow milk allergy in Australia.

PubMed

Guest, J F; Nagy, E

2009-02-01

To estimate the resource implications and budget impact of current clinical practice for managing cow milk allergy (CMA) in Australia, from the perspective of the publicly funded healthcare system. A decision model was constructed using published clinical outcomes and clinician-derived resource utilisation estimates. The model was used to estimate the expected 6-monthly levels of healthcare resource use and corresponding costs attributable to managing 6150 new CMA sufferers following referral to a specialist. The expected 6-monthly costs of managing 6150 newly-diagnosed infants with CMA following referral to a specialist was an estimated (Australian dollars, AU$) AU$6.5 million at 2006/07 prices. Clinical nutrition preparations were found to be the primary cost driver accounting for 62% of the total 6-monthly cost and clinician visits were the secondary cost driver accounting for up to a further 28% of the total 6-monthly cost. Sensitivity analysis showed there would be fewer visits to hospital-based paediatric gastroenterologists and paediatric immunologists/allergists if all newly-diagnosed patients were prescribed an amino acid formula (AAF) following referral to a specialist, instead of being managed according to current practice. CMA imposes a substantial burden on the publicly funded healthcare system in Australia. However, using an AAF as the initial treatment for CMA can potentially release limited hospital resources for alternative use within the paediatric healthcare system.

Statin-associated immune-mediated myopathy: biology and clinical implications.

PubMed

Christopher-Stine, Lisa; Basharat, Pari

2017-04-01

In the last 6 years, our understanding of statin-associated myopathy expanded to include not only a toxic myopathy with limited and reversible side-effects but also an autoimmune variety in which statins likely induce an autoimmune myopathy that is both associated with a specific autoantibody and responsive to immunosuppression and immune modulation. This review widens the reader's understanding of statin myopathy to include an autoimmune process. Statin-associated immune-mediated myopathy provides an example of an environmental trigger (statins) directly implicated in an autoimmune disease associated with a genetic predisposition as well as potential risk factors including concomitant diseases and specific statins. Given a median exposure to statins of 38 months, providers should be aware that anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) myopathy may occur even after several years of statin exposure. It is important for the reader to understand the clinical presentation of statin-associated immune-mediated myopathy and the difference in its clinical presentation to that of statins as direct myotoxins. Prompt recognition of such an entity allows the clinician to immediately stop the offending agent if it has not already been discontinued as well as to recognize that statin rechallenge is not a likely option, and that prompt treatment with immunosuppression and/or immunomodulation is usually of enormous benefit to the patient in restoring muscle strength and physical function. VIDEO ABSTRACT.

Ultraviolet light-induced keratinocyte apoptosis: a potential mechanism for the induction of skin lesions and autoantibody production in LE.

PubMed

Casciola-Rosen, L; Rosen, A

1997-01-01

Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease which is characterized clinically by pleiotropy and periodicity. The immune features which accompany the characteristic flares of the disease have strongly suggested that the autoimmune response is driven by self antigen, and is T cell-dependent. These features have prompted the search for potential initiating process(es) which induce the release of self-antigens in a form which causes T cell tolerance to those self molecules to be broken. We review here several recent observations which implicate apoptotic cells as an important potential source of clustered and concentrated autoantigens in SLE, and present our current model whereby the novel autoantigen fragments generated in apoptotic surface blebs initiate and drive the autoimmune response in this disease.

Computerised mirror therapy with Augmented Reflection Technology for early stroke rehabilitation: clinical feasibility and integration as an adjunct therapy.

PubMed

Hoermann, Simon; Ferreira Dos Santos, Luara; Morkisch, Nadine; Jettkowski, Katrin; Sillis, Moran; Devan, Hemakumar; Kanagasabai, Parimala S; Schmidt, Henning; Krüger, Jörg; Dohle, Christian; Regenbrecht, Holger; Hale, Leigh; Cutfield, Nicholas J

2017-07-01

New rehabilitation strategies for post-stroke upper limb rehabilitation employing visual stimulation show promising results, however, cost-efficient and clinically feasible ways to provide these interventions are still lacking. An integral step is to translate recent technological advances, such as in virtual and augmented reality, into therapeutic practice to improve outcomes for patients. This requires research on the adaptation of the technology for clinical use as well as on the appropriate guidelines and protocols for sustainable integration into therapeutic routines. Here, we present and evaluate a novel and affordable augmented reality system (Augmented Reflection Technology, ART) in combination with a validated mirror therapy protocol for upper limb rehabilitation after stroke. We evaluated components of the therapeutic intervention, from the patients' and the therapists' points of view in a clinical feasibility study at a rehabilitation centre. We also assessed the integration of ART as an adjunct therapy for the clinical rehabilitation of subacute patients at two different hospitals. The results showed that the combination and application of the Berlin Protocol for Mirror Therapy together with ART was feasible for clinical use. This combination was integrated into the therapeutic plan of subacute stroke patients at the two clinical locations where the second part of this research was conducted. Our findings pave the way for using technology to provide mirror therapy in clinical settings and show potential for the more effective use of inpatient time and enhanced recoveries for patients. Implications for Rehabilitation Computerised Mirror Therapy is feasible for clinical use Augmented Reflection Technology can be integrated as an adjunctive therapeutic intervention for subacute stroke patients in an inpatient setting Virtual Rehabilitation devices such as Augmented Reflection Technology have considerable potential to enhance stroke rehabilitation.

Clinical implications of contemporary gender theory.

PubMed

Kulish, Nancy

2010-04-01

The current intellectual scene in psychoanalysis is marked by vigorous theoretical controversies about gender. The ideas being debated have important implications for clinical work, which have not been thoroughly explicated or integrated into common practice. These implications include the following: gender can accrue idiosyncratic meanings; gender identity is considered fluid and rigidity of gender identity deemed problematic; gender-related conflicts are typically described as divergent; analysis of superego conflicts related to gender becomes particularly important; and, finally, gender-related biases are seen as inevitable and must be taken into account in the clinical situation. A detailed clinical example illustrates the application of these ideas. While the more dramatic cases related to gender have been more frequent subjects of study, conflicts about gender are everyday occurrences for our patients and deserve further attention.

Multi-scale analysis of neural activity in humans: Implications for micro-scale electrocorticography.

PubMed

Kellis, Spencer; Sorensen, Larry; Darvas, Felix; Sayres, Conor; O'Neill, Kevin; Brown, Richard B; House, Paul; Ojemann, Jeff; Greger, Bradley

2016-01-01

Electrocorticography grids have been used to study and diagnose neural pathophysiology for over 50 years, and recently have been used for various neural prosthetic applications. Here we provide evidence that micro-scale electrodes are better suited for studying cortical pathology and function, and for implementing neural prostheses. This work compares dynamics in space, time, and frequency of cortical field potentials recorded by three types of electrodes: electrocorticographic (ECoG) electrodes, non-penetrating micro-ECoG (μECoG) electrodes that use microelectrodes and have tighter interelectrode spacing; and penetrating microelectrodes (MEA) that penetrate the cortex to record single- or multiunit activity (SUA or MUA) and local field potentials (LFP). While the finest spatial scales are found in LFPs recorded intracortically, we found that LFP recorded from μECoG electrodes demonstrate scales of linear similarity (i.e., correlation, coherence, and phase) closer to the intracortical electrodes than the clinical ECoG electrodes. We conclude that LFPs can be recorded intracortically and epicortically at finer scales than clinical ECoG electrodes are capable of capturing. Recorded with appropriately scaled electrodes and grids, field potentials expose a more detailed representation of cortical network activity, enabling advanced analyses of cortical pathology and demanding applications such as brain-computer interfaces. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Enabling Anyone to Translate Clinically Relevant Ideas to Therapies.

PubMed

Ekins, Sean; Diaz, Natalie; Chung, Julia; Mathews, Paul; McMurtray, Aaron

2017-01-01

How do we inspire new ideas that could lead to potential treatments for rare or neglected diseases, and allow for serendipity that could help to catalyze them? How many potentially good ideas are lost because they are never tested? What if those ideas could have lead to new therapeutic approaches and major healthcare advances? If a clinician or anyone for that matter, has a new idea they want to test to develop a molecule or therapeutic that they could translate to the clinic, how would they do it without a laboratory or funding? These are not idle theoretical questions but addressing them could have potentially huge economic implications for nations. If we fail to capture the diversity of ideas and test them we may also lose out on the next blockbuster treatments. Many of those involved in the process of ideation may be discouraged and simply not know where to go. We try to address these questions and describe how there are options to raising funding, how even small scale investments can foster preclinical or clinical translation, and how there are several approaches to outsourcing the experiments, whether to collaborators or commercial enterprises. While these are not new or far from complete solutions, they are first steps that can be taken by virtually anyone while we work on other solutions to build a more concrete structure for the "idea-hypothesis testing-proof of concept-translation-breakthrough pathway".

IGF system targeted therapy: Therapeutic opportunities for ovarian cancer.

PubMed

Liefers-Visser, J A L; Meijering, R A M; Reyners, A K L; van der Zee, A G J; de Jong, S

2017-11-01

The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models. In addition, anti-IGF-1R targeted strategies potentiated the efficacy of platinum based chemotherapy. Despite the vast amount of encouraging and promising pre-clinical data, anti-IGF-1R/IR targeted strategies lacked efficacy in the clinic. The question is whether targeting the IGF-1R/IR signaling pathway still holds therapeutic potential. In this review we address the complexity of the IGF-1R/IR signaling pathway, including receptor heterodimerization within and outside the IGF system and downstream signaling. Further, we discuss the implications of this complexity on current targeted strategies and indicate therapeutic opportunities for successful targeting of the IGF-1R/IR signaling pathway in ovarian cancer. Multiple-targeted approaches circumventing bidirectional receptor tyrosine kinase (RTK) compensation and prevention of system rewiring are expected to have more therapeutic potential. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Aortic stenosis: insights on pathogenesis and clinical implications

PubMed Central

Carità, Patrizia; Coppola, Giuseppe; Novo, Giuseppina; Caccamo, Giuseppa; Guglielmo, Marco; Balasus, Fabio; Novo, Salvatore; Castrovinci, Sebastiano; Moscarelli, Marco; Fattouch, Khalil; Corrado, Egle

2016-01-01

Aortic stenosis (AS) is a common valvular heart disease in the Western populations, with an estimated overall prevalence of 3% in adults over 75 years. To understand its patho-biological processes represents a priority. In elderly patients, AS usually involves trileaflet valves and is referred to as degenerative calcific processes. Scientific evidence suggests the involvement of an active “atherosclerosis-like” pathogenesis in the initiation phase of degenerative AS. To the contrary, the progression could be driven by different forces (such as mechanical stress, genetic factors and interaction between inflammation and calcification). The improved understanding presents potentially new therapeutic targets for preventing and inhibiting the development and progression of the disease. Furthermore, in clinical practice the management of AS patients implies the evaluation of generalized atherosclerotic manifestations (i.e., in the coronary and carotid arteries) even for prognostic reasons. In counselling elderly patients, the risk stratification should address individual frailty beyond the generic risk scores. In these regard, the co-morbidities, and in particular those linked to the global atherosclerotic burden, should be carefully investigated in order to define the risk/benefit ratio for invasive treatment strategies. We present a detailed overview of insights in pathogenesis of AS with possible practical implications. PMID:27582763

Medicolegal implications of surgical errors and complications in neck surgery: A review based on the Italian current legislation

PubMed Central

Polistena, Andrea; Sanguinetti, Alessandro; Buccelli, Claudio; Conzo, Giovanni; Conti, Adelaide; Niola, Massimo; Avenia, Nicola

2016-01-01

Abstract Aim of the present paper is the review of the principal complications associated to endocrine neck surgery considering how expertise, full adoption of guidelines, appropriate technology and proper informed consent may limit the medicolegal claims at the light of the incoming new regulation of the medical professional legal responsibility. A literature search, using the Medline/PubMed database for full-length papers, was used. Postoperative recurrent laryngeal nerve (RLN) palsy and hypoparathy-roidism remain the principal causes of surgical malpractice claims . In the procedure of neck lymphadenctomy intra-operative haemorrhage, thoracic duct injury, injuries to loco-regional nerves can be observed and can be source of claims. After many years of increased medicolegal litigations, the Italian government is proposing a drastic change in the regulations of supposed medical malpractice in order to guarantee the patient’s right to a safe treatment and in the meantime to defend clinicians from often unmotivated and prejudicial legal cases. Surgical errors and complications in neck surgery are a relevant clinical issue. Only the combination of surgical and clinical expertise, application of guidelines, appropriate technology and a routinely use of specific informed consent can contain potential medicolegal implications. PMID:28352812

Fusion proteins in head and neck neoplasms: Clinical implications, genetics, and future directions for targeting

PubMed Central

Escalante, Derek A.; Wang, He; Fundakowski, Christopher E.

2016-01-01

ABSTRACT Fusion proteins resulting from chromosomal rearrangements are known to drive the pathogenesis of a variety of hematological and solid neoplasms such as chronic myeloid leukemia and non-small-cell lung cancer. Efforts to elucidate the role they play in these malignancies have led to important diagnostic and therapeutic triumphs, including the famous development of the tyrosine kinase inhibitor dasatinib targeting the BCR-ABL fusion. Until recently, there has been a paucity of research investigating fusion proteins harbored by head and neck neoplasms. The discovery and characterization of novel fusion proteins in neoplasms originating from the thyroid, nasopharynx, salivary glands, and midline head and neck structures offer substantial contributions to our understanding of the pathogenesis and biological behavior of these neoplasms, while raising new therapeutic and diagnostic opportunities. Further characterization of these fusion proteins promises to facilitate advances on par with those already achieved with regard to hematologic malignancies in the precise, molecularly guided diagnosis and treatment of head and neck neoplasms. The following is a subsite specific review of the clinical implications of fusion proteins in head and neck neoplasms and the future potential for diagnostic targeting. PMID:27636353

An overview of concussion in sport.

PubMed

Khurana, Vini G; Kaye, Andrew H

2012-01-01

Concussion is a sudden-onset, transient alteration of consciousness due to a combination of functional and structural brain disturbances following a physical impact transmitted to the brain. It is a common, although likely underreported, condition encountered in a wide range of sports. In the Australian Football League, concussion is estimated to occur at a rate of approximately seven injuries per team per season. While many instances of concussion are clinically mild, there is emerging evidence that a player's full recovery from a concussive injury may be more delayed and the sequelae of repeated concussions more severe than previously thought. In this light, a more conservative and rigorous approach to managing players with concussive injuries may be warranted, with the guiding principle being the player's immediate and long-term welfare. The current paper reviews the sports concussion literature. The definition, epidemiology, aetiology, pathophysiology, structural pathology, clinical features, assessment and investigation, treatment principles, and short-term and potential long-term complications of concussion are discussed. Special considerations in paediatric sports concussion, and the return-to-play implications of immediate, evolving and repetitive brain injury are also considered, as are the emerging concept and possible implications of subconcussive injury. Copyright © 2011 Elsevier Ltd. All rights reserved.

Understanding attention deficit hyperactivity disorder as a continuum

PubMed Central

McLennan, John D.

2016-01-01

Abstract Objective To review research findings that consider whether attention deficit hyperactivity disorder (ADHD) is a discrete entity or whether it is more consistent with an extreme end-of-trait distribution in the population and to then grapple with the potential clinical implications. Quality of evidence Peer-reviewed publications in the past 5 years, drawing from diverse fields (taxonomy, epidemiology, genetics, neurobiology, and neuropsychology), were identified through searches in MEDLINE and PsycINFO. Main message Accumulating research findings are most consistent with a predominately dimensional rather than a qualitatively distinct existence for ADHD. This does not negate the clinical needs of those who have substantial ADHD symptom clusters, nor the risks that such symptoms entail. However, the lack of discontinuity in the distribution of such traits in the population creates great uncertainty as to what thresholds should prompt explicit intervention. Conclusion The implications of this pattern of findings might include the need to de-emphasize categorical conceptualizations of ADHD, produce evidence to better inform risk-benefit ratios of interventions along a spectrum of symptom and functional severity, and more coherently triage and arrange service delivery on the basis of symptom and functional severity rather than artificial diagnostic categorizations. PMID:27965331

Understanding the properties of common dietary supplements: clinical implications for healthcare practitioners.

PubMed

Zelig, Rena; Rigassio Radler, Diane

2012-12-01

Dietary supplement usage in the United States continues to increase. This article explores the background of dietary supplements and their regulations, discusses trends in usage patterns highlighting the properties of 10 popular dietary supplements, addresses safety concerns and drug-nutrient interactions, and discusses the role of the healthcare professional in assessing and recommending usage of dietary supplements. The authors reviewed the literature on dietary supplementation. Government websites were used to obtain background and regulatory information. Evidence-based databases were used to summarize popular dietary supplements in terms of their common uses, mechanisms of action, and clinical implications. The related literature was reviewed to discuss important factors for the healthcare professional to consider as well as the role of the healthcare professional in integrating dietary supplement use within patient care. Healthcare professionals need to be prepared to evaluate dietary supplement usage and make appropriate recommendations for an individualized plan of care. As the popularity of dietary supplements continues to grow, healthcare professionals will need to communicate with patients about their usage; educate themselves on their potential benefits, interactions, and contraindications; evaluate the literature; make recommendations; and document appropriately in a comprehensive and integrated plan of care.

The Role of Serotonin (5-HT) in Behavioral Control: Findings from Animal Research and Clinical Implications

PubMed Central

Sanchez, CL; Biskup, CS; Herpertz, S; Gaber, TJ; Kuhn, CM; Hood, SH

2015-01-01

The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research. PMID:25991656

Intrarenal urea recycling leads to a higher rate of renal excretion of potassium: an hypothesis with clinical implications.

PubMed

Kamel, Kamel S; Halperin, Mitchell L

2011-09-01

This review aims to illustrate why urea recycling may play an important role in potassium (K⁺) excretion and to emphasize its potential clinical implications. A quantitative analysis of the process of intrarenal urea recycling reveals that the amount of urea delivered to the distal convoluted tubule is about two-fold larger than the quantity of urea excreted in the urine. As the number of osmoles delivered to the late cortical distal nephron (CCD) determines its flow rate when aquaporin 2 water channels have been inserted in the luminal membrane of principal cells, urea recycling may play an important role in regulating the rate of excretion of K⁺ when the distal delivery of electrolytes is not very high. Urea recycling aids the excretion of K⁺; this is especially important in patients with disorders or those who are taking drugs that lead to a less lumen-negative voltage in the CCD. As a large quantity of urea is reabsorbed daily in the inner medullary collecting duct, the assumption made in the calculation of the transtubular K concentration gradient that there is no appreciable reabsorption of osmoles downstream CCD is not valid.

Neuroendocrine and neurotrophic signaling in Huntington's disease: Implications for pathogenic mechanisms and treatment strategies.

PubMed

Bartlett, Danielle M; Cruickshank, Travis M; Hannan, Anthony J; Eastwood, Peter R; Lazar, Alpar S; Ziman, Mel R

2016-12-01

Huntington's disease (HD) is a fatal neurodegenerative disease caused by an extended polyglutamine tract in the huntingtin protein. Circadian, sleep and hypothalamic-pituitary-adrenal (HPA) axis disturbances are observed in HD as early as 15 years before clinical disease onset. Disturbances in these key processes result in increased cortisol and altered melatonin release which may negatively impact on brain-derived neurotrophic factor (BDNF) expression and contribute to documented neuropathological and clinical disease features. This review describes the normal interactions between neurotrophic factors, the HPA-axis and circadian rhythm, as indicated by levels of BDNF, cortisol and melatonin, and the alterations in these intricately balanced networks in HD. We also discuss the implications of these alterations on the neurobiology of HD and the potential to result in hypothalamic, circadian, and sleep pathologies. Measurable alterations in these pathways provide targets that, if treated early, may reduce degeneration of brain structures. We therefore focus here on the means by which multidisciplinary therapy could be utilised as a non-pharmaceutical approach to restore the balance of these pathways. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Age and rate of cognitive decline in Alzheimer disease: implications for clinical trials.

PubMed

Bernick, Charles; Cummings, Jeffrey; Raman, Rema; Sun, Xiaoying; Aisen, Paul

2012-07-01

Factors that affect the rate of progression of Alzheimer disease (AD) need to be considered in the clinical trial designs of potential disease-modifying therapies. To determine the influence of age on AD course in a clinical trial setting. Pooled cohort study from 3 AD clinical trials of 18-month duration conducted by the Alzheimer Disease Cooperative Study group. Alzheimer disease research centers from across the United States. Four hundred seventy-one subjects with mild to moderate AD assigned to the placebo arm of 3 clinical trials. The relationships between baseline age and rate of change in the Alzheimer Disease Assessment Scale–cognitive subscale (ADAS-cog) 11, Mini-Mental State Examination, Clinical Dementia Rating scale Sum of Boxes score, Alzheimer Disease Cooperative Study–activities of daily living scale, and Neuropsychiatric Inventory were analyzed using a mixed-effect regression model. Sample size calculation for possible future AD clinical trials lasting 18 months using the results of the change in ADAS-cog 11 by tertiles of age groups. Older age at baseline was associated with a slower rate of decline in the ADAS-cog 11 and the Mini-Mental State Examination scores. Almost twice as many subjects aged 80 years and older compared with those aged younger than 70 years would be required to demonstrate a 30% treatment effect on the ADAS-cog 11 in an 18-month AD trial. Subject age is an important factor to consider when defining the study population in and analyzing data from AD trials of potential disease-modifying therapies.

A regional interdependence model of musculoskeletal dysfunction: research, mechanisms, and clinical implications

PubMed Central

Sueki, Derrick G; Cleland, Joshua A; Wainner, Robert S

2013-01-01

The term ‘regional interdependence’ or RI has recently been introduced into the vernacular of physical therapy and rehabilitation literature as a clinical model of musculoskeletal assessment and intervention. The underlying premise of this model is that seemingly unrelated impairments in remote anatomical regions of the body may contribute to and be associated with a patient’s primary report of symptoms. The clinical implication of this premise is that interventions directed at one region of the body will often have effects at remote and seeming unrelated areas. The formalized concept of RI is relatively new and was originally derived in an inductive manner from a variety of earlier publications and clinical observations. However, recent literature has provided additional support to the concept. The primary purpose of this article will be to further refine the operational definition for the concept of RI, examine supporting literature, discuss possible clinically relevant mechanisms, and conclude with a discussion of the implications of these findings on clinical practice and research. PMID:24421619

Severe acute respiratory syndrome: implications for perinatal and neonatal nurses.

PubMed

Rebmann, Terri

2005-01-01

Severe acute respiratory syndrome (SARS) is an emerging infection that causes a potentially fatal respiratory disease. Although the SARS outbreak lasted less than 1 year, it resulted in significant morbidity and mortality and impacted nursing practices. A literature review was conducted. Only English language research articles in peer-reviewed journals, national organization publications, and book chapters were utilized. Data from 37 relevant articles were extracted, analyzed, and summarized. SARS' clinical description is presented, including its common signs/symptoms, diagnosis, and treatment. Recommended isolation practices for labor and delivery and proper procedures for donning, using, and doffing personal protective equipment are provided. Potential maternal outcomes include spontaneous miscarriage during the first trimester, preterm birth, emergency cesarean section, renal failure, secondary bacterial pneumonia, sepsis, adult respiratory distress syndrome, disseminated intravascular coagulation, surgical site infection, and maternal death. There have been no documented cases of vertical transmission; passive immunity is suspected on the basis of the presence of antibodies in some maternal body fluids. Potential neonatal outcomes include complications related to premature birth, intrauterine growth restriction, respiratory distress syndrome, and severe gastrointestinal manifestations. It is not known if or when SARS will reemerge, but perinatal and neonatal nurses should become familiar with its clinical description and proper infection control procedures to halt potential outbreaks.

Ebola: Implications and Perspectives

PubMed Central

Del Rio, Carlos; Guarner, Jeannette

2015-01-01

The 2014 Ebola virus disease outbreak in West Africa has been the largest in recorded history. During this Ebola epidemic, the media has focused much attention to the magnitude of the problem in West Africa but has also overplayed the potential for an Ebola virus pandemic as patients have been transported for treatment to the United States and Europe causing panic and paranoia in the population. Knowledge of the epidemiology, pathogenesis, clinical presentation, treatment, and prevention of this infection will allow a better understanding of the disease and decrease irrational fear of spread. PMID:26330663

The impact of hepatitis A virus infection on hepatitis C virus infection: a competitive exclusion hypothesis.

PubMed

Amaku, Marcos; Coutinho, Francisco Antonio Bezerra; Chaib, Eleazar; Massad, Eduardo

2013-01-01

We address the observation that, in some cases, patients infected with the hepatitis C virus (HCV) are cleared of HCV when super-infected with the hepatitis A virus (HAV). We hypothesise that this phenomenon can be explained by the competitive exclusion principle, including the action of the immune system, and show that the inclusion of the immune system explains both the elimination of one virus and the co-existence of both infections for a certain range of parameters. We discuss the potential clinical implications of our findings.

Memory Reconsolidation.

PubMed

Haubrich, Josue; Nader, Karim

2018-01-01

Scientific advances in the last decades uncovered that memory is not a stable, fixed entity. Apparently stable memories may become transiently labile and susceptible to modifications when retrieved due to the process of reconsolidation. Here, we review the initial evidence and the logic on which reconsolidation theory is based, the wide range of conditions in which it has been reported and recent findings further revealing the fascinating nature of this process. Special focus is given to conceptual issues of when and why reconsolidation happen and its possible outcomes. Last, we discuss the potential clinical implications of memory modifications by reconsolidation.

Dissociative states in dreams and brain chaos: implications for creative awareness

PubMed Central

Bob, Petr; Louchakova, Olga

2015-01-01

This article reviews recent findings indicating some common brain processes during dissociative states and dreaming with the aim to outline a perspective that neural chaotic states during dreaming can be closely related to dissociative states that may manifest in dreams scenery. These data are in agreement with various clinical findings that dissociated states can be projected into the “dream scenery” in REM sleep periods and dreams may represent their specific interactions that may uncover unusual psychological potential of creativity in psychotherapy, art, and scientific discoveries. PMID:26441729

Recent Advances in Attention Bias Modification for Substance Addictions

PubMed Central

Zhang, Melvyn Weibin; Ying, Jiang Bo; Song, Guo; Fung, Daniel S. S.; Smith, Helen E.

2018-01-01

Research on attentional bias modification has increased since 2014. A recent meta-analysis demonstrates evidence for bias modification for substance disorders, including alcohol and tobacco use disorders. Several pharmacological trials have shown that pharmacological agents can attenuate and modify such attentional bias. The pharmacological trials that have appeared to date have produced mixed results, which has clinical implications. Developments in Internet and mobile technologies have transformed how attention bias modification is currently being achieved. There remains great potential for further research that examines the efficacy of technology-aided attention bias interventions. PMID:29617325

Gene delivery for cancer therapy.

PubMed

Zhang, Teng

2014-01-01

Gene therapy has potential in the treatment of human cancers. However, its clinical implication has only achieved little success due to the lack of an efficient gene delivery system. A major hurdle in the current available approaches is in the ability to transduce target tissues at very high efficiencies that ultimately lead to therapeutic levels of transgene expression. This review outlines the characteristics and utilities of several available gene delivery systems, including their advantages and drawbacks in the context of cancer treatment. A perspective of existing challenges and future directions is also included.

Post-Operative Cognitive Dysfunction: An exploration of the inflammatory hypothesis and novel therapies.

PubMed

Skvarc, David R; Berk, Michael; Byrne, Linda K; Dean, Olivia M; Dodd, Seetal; Lewis, Matthew; Marriott, Andrew; Moore, Eileen M; Morris, Gerwyn; Page, Richard S; Gray, Laura

2018-01-01

Post-Operative Cognitive Dysfunction (POCD) is a highly prevalent condition with significant clinical, social and financial impacts for patients and their communities. The underlying pathophysiology is becoming increasingly understood, with the role of neuroinflammation and oxidative stress secondary to surgery and anaesthesia strongly implicated. This review aims to describe the putative mechanisms by which surgery-induced inflammation produces cognitive sequelae, with a focus on identifying potential novel therapies based upon their ability to modify these pathways. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Investor Outlook: Focus on Upcoming LCA2 Gene Therapy Phase III Results.

PubMed

Schimmer, Joshua; Breazzano, Steven

2015-09-01

Investor interest in gene therapy has increased substantially over the past few years, and the next major catalyst for the field is likely to be Spark Therapeutics's phase III trial for the treatment of visual impairment caused by RPE65 gene mutations (often referred to as Leber congenital amaurosis type 2, or LCA2, but may include other retinal disorders). Analysis of the approach from the basic genetics, underlying visual mechanisms, clinical data, and commercialization considerations helps frame investor expectations and the potential implications for the broader field.

Update on obstructive sleep apnea and its relation to COPD

PubMed Central

Mieczkowski, Brian; Ezzie, Michael E

2014-01-01

Chronic obstructive pulmonary disease (COPD) is a common and preventable lung disease that affects millions of people in the United States. Sleep disorders including obstructive sleep apnea (OSA) are also common. It is not surprising that many people with COPD also suffer from OSA. This relationship, however, puts people at risk for more nocturnal desaturations and potential complications related to this, including pulmonary hypertension and heart rhythm disturbances. This update focuses on the physiology of sleep disturbances in COPD as well as the clinical implications of OSA in COPD. PMID:24748786

A retrospective analysis of employee turnover in the health care setting.

PubMed

Bednar, B; McMullen, N

1998-02-01

Significant factors implicated in staff turnover include: variables in organizational structure; employee characteristics; needs and values, and the nature of tasks performed. This article will present the causative factors related to turnover and the conceptual models of the motivational theorists Maslow, Herzberg, Adams, and Mobley. No quantitative or qualitative research could be found on the potential causes of turnover in freestanding dialysis clinics. The staff turnover of a for-profit dialysis company for a 12 month period will be reported by job title, tenure, and level of job satisfaction.

[Psychosocial interventions in dementia].

PubMed

Kurz, A

2013-01-01

Psychosocial interventions improve cognitive abilities (cognitive stimulation, cognitive training), enhance emotional well-being (activity planning, reminiscence), reduce behavioral symptoms (aromatherapy, music therapy) and promote everyday functioning (occupational therapy). Through these effects they reinforce and augment pharmacological treatments for dementia. In addition, psychosocial interventions complement the treatment of patients by supporting family caregivers (educational groups, support programs). The potential of psychosocial interventions in dementia needs to be explored further in studies using improved methodology to determine effective components, clinical relevance and duration of effects, predictors of individual treatment response and health-economic implications.

Analysis and Application of the Concept of Modesty to Breastfeeding

PubMed Central

Moran, Meghan

1999-01-01

Modesty may be a significant variable impacting breast- feeding outcomes in western cultures, yet this term has received minimal attention in the breastfeeding literature. An analysis of the concept of modesty was conducted to gain greater understanding of the potential impact of modesty on breastfeeding outcomes. Various uses of the term modesty and particularly modesty in the context of breastfeeding are discussed in this paper. The defining attributes of breastfeeding modesty are identified and examples are provided. Implications for research and clinical practice are suggested. PMID:22988417

Epistemic cognition in medical education: a literature review.

PubMed

Eastwood, Jennifer L; Koppelman-White, Elysa; Mi, Misa; Wasserman, Jason Adam; Krug Iii, Ernest F; Joyce, Barbara

2017-01-07

To review the research literature on epistemic cognition in medical education. We conducted database searches using keywords related to epistemic cognition and medical education or practice. In duplicate, authors selected and reviewed empirical studies with a central focus on epistemic cognition and participant samples including medical students or physicians. Independent thematic analysis and consensus procedures were used to identify major findings about epistemic cognition and implications for research and medical education. Twenty-seven articles were selected. Themes from the findings of selected studies included developmental frameworks of epistemic cognition revealing simple epistemological positions of medical learners, increasing epistemological sophistication with experience, relationships between epistemic cognition and context, patterns in epistemic orientations to clinical practice, and reactions to ambiguity and uncertainty. Many studies identified the need for new instruments and methodologies to study epistemic cognition in medical education settings and its relationship to clinical outcomes. Relationships between epistemological beliefs and humanistic patient care and influences of medical education practices were commonly cited implications for medical education. Epistemic cognition is conceptualized and operationalized in a variety of ways in the medical research literature. Advancing theoretical frameworks and developing new methodological approaches to examine epistemic cognition are important areas for future research. Also, examination of the relationship between the contexts of medical learning and practice and epistemic cognition has potential for improving medical education. This work also establishes a need for further investigation into the implications of epistemic cognition for humanistic orientations and ultimately for patient care.

Exposure to traumatic perinatal experiences and posttraumatic stress symptoms in midwives: prevalence and association with burnout.

PubMed

Sheen, Kayleigh; Spiby, Helen; Slade, Pauline

2015-02-01

Midwives provide care in a context where life threatening or stressful events can occur. Little is known about their experiences of traumatic events or the implications for psychological health of this workforce. To investigate midwives' experiences of traumatic perinatal events encountered whilst providing care to women, and to consider potential implications. A national postal survey of UK midwives was conducted. 421 midwives with experience of a perinatal event involving a perceived risk to the mother or baby which elicited feelings of fear, helplessness or horror (in the midwife) completed scales assessing posttraumatic stress symptoms, worldview beliefs and burnout. 33% of midwives within this sample were experiencing symptoms commensurate with clinical posttraumatic stress disorder. Empathy and previous trauma exposure (personal and whilst providing care to women) were associated with more severe posttraumatic stress responses. However, predictive utility was limited, indicating a need to consider additional aspects increasing vulnerability. Symptoms of posttraumatic stress were associated with negative worldview beliefs and two domains of burnout. Midwives may experience aspects of their work as traumatic and, as a consequence, experience posttraumatic stress symptomatology at clinical levels. This holds important implications for both midwives' personal and professional wellbeing and the wellbeing of the workforce, in addition to other maternity professionals with similar roles and responsibilities. Organisational strategies are required to prepare midwives for such exposure, support midwives following traumatic perinatal events and provide effective intervention for those with significant symptoms. Copyright © 2014 Elsevier Ltd. All rights reserved.

Epistemic cognition in medical education: a literature review

PubMed Central

Koppelman-White, Elysa; Mi, Misa; Wasserman, Jason Adam; Krug III, Ernest F.; Joyce, Barbara

2017-01-01

Objective To review the research literature on epistemic cognition in medical education. Methods We conducted database searches using keywords related to epistemic cognition and medical education or practice. In duplicate, authors selected and reviewed empirical studies with a central focus on epistemic cognition and participant samples including medical students or physicians. Independent thematic analysis and consensus procedures were used to identify major findings about epistemic cognition and implications for research and medical education. Results Twenty-seven articles were selected. Themes from the findings of selected studies included developmental frameworks of epistemic cognition revealing simple epistemological positions of medical learners, increasing epistemological sophistication with experience, relationships between epistemic cognition and context, patterns in epistemic orientations to clinical practice, and reactions to ambiguity and uncertainty. Many studies identified the need for new instruments and methodologies to study epistemic cognition in medical education settings and its relationship to clinical outcomes. Relationships between epistemological beliefs and humanistic patient care and influences of medical education practices were commonly cited implications for medical education. Conclusions Epistemic cognition is conceptualized and operationalized in a variety of ways in the medical research literature. Advancing theoretical frameworks and developing new methodological approaches to examine epistemic cognition are important areas for future research. Also, examination of the relationship between the contexts of medical learning and practice and epistemic cognition has potential for improving medical education. This work also establishes a need for further investigation into the implications of epistemic cognition for humanistic orientations and ultimately for patient care. PMID:28064257

Correlates of Quality of Life among African American and White Cancer Survivors

PubMed Central

Matthews, Alicia K.; Tejeda, Silvia; Johnson, Timothy P.; Berbaum, Michael L.; Manfredi, Clara

2013-01-01

Background African Americans continue to suffer disproportionately from cancer morbidity and mortality with emerging evidence suggesting potential quality of life (QOL) disparities in the survivorship period. Objective To assess sociodemographic, clinical, and psychosocial factors associated with physical and mental health QOL (PHQOL and MHQOL) among African American and white cancer survivors. Methods Patients were recruited from tumor registries. Telephone interviews were conducted with 248 African American and 244 white respondents with a history of breast, prostate, or colorectal cancers. Multivariate regression models were used to assess what factors were associated with PHQOL and MHQOL. Results Key racial differences in adjusted analyses included poorer MHQOL scores among African Americans compared to white survivors. Furthermore, race moderated the relationship between perceived social support and MHQOL, where higher social support levels were associated with increased MHQOL among African Americans. Other correlates of QOL impacted racial groups similarly. For example, factors associated with PHQOL scores included being unemployed, uninsured, the presence of medical comorbidities, a longer time since diagnosis and higher levels of cancer related stress appraisals. Factors associated with MHQOL scores included being unemployed, higher levels of daily stress, higher levels of stress associated with the diagnosis, higher levels of education, higher levels of perceived social support, and higher levels of spirituality. Conclusion Interventions aimed at increasing social support may have important implications for improving QOL outcomes among African Americans. Implications for Practice Measuring and understanding factors associated with QOL have important implications for patient adjustment and clinical decision-making. PMID:22495496

Vitamin D in the Pathophysiology of Hypertension, Kidney Disease, and Diabetes: Examining the Relationship Between Vitamin D and the Renin-Angiotensin System in Human Diseases

PubMed Central

Vaidya, Anand; Williams, Jonathan S.

2011-01-01

Objective Vitamin D has been implicated in the pathophysiology of extra-skeletal conditions such as hypertension, kidney disease, and diabetes, via its ability to negatively regulate the renin-angiotensin system (RAS). This article reviews the evidence supporting a link between vitamin D and the RAS in these conditions, with specific emphasis on translational observations and their limitations. Methods Literature review of animal and human studies evaluating the role of vitamin D in hypertension, kidney disease, and diabetes. Results Excess activity of the RAS has been implicated in the pathogenesis of hypertension, chronic kidney disease, decreased insulin secretion, and insulin resistance. Animal studies provide strong support for 1,25(OH)2D mediated down-regulation of renin expression and RAS activity via its interaction with the vitamin D receptor. Furthermore, the activity of vitamin D metabolites in animals is associated with reductions in blood pressure, proteinuria and renal injury, and with improved β–cell function. Many observational, and a few interventional, studies in humans have supported these findings; however, there is a lack of well designed prospective human interventional studies to definitively assess clinical outcomes. Conclusion Animal studies implicate vitamin D receptor agonist therapy to lower RAS activity as a potential method to reduce the risk of hypertension, kidney disease, and diabetes. There is a need for more well designed prospective interventional studies to validate this hypothesis in human clinical outcomes. PMID:22075270

Therapeutic Body Wraps in Swiss public adult acute inpatient wards. A retrospective descriptive cohort study.

PubMed

Opsommer, E; Dubois, J; Bangerter, G; Panchaud, R; Martin, D; Skuza, K

2016-04-01

WHAT IS KNOWN ON THE SUBJECT?: Various expert opinions reported relational benefits and tranquilizing effects of therapeutic body wraps (TBW) in adults experiencing high anxiety in the context of psychosis. Yet, this tranquilizing effect was never investigated in larger samples and in the context of modern psychopharmacology. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This is the first study to establish descriptive statistics of this mind-body therapy in French-speaking Switzerland where TBWs are routinely used in two public psychiatric hospitals. It brings knowledge on patients nowadays treated with TBW. Moreover, it opens a new area of investigation on the potential of this nursing technique, which may contribute to reduce anxiolytic medication in severely ill patients. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: This study sheds light on a clinical practice in mental health nursing and upon nurses' specific contribution to psychiatric clinic. It investigates a potential for TBWs to reduce the use of anxiolytic medications by patients who agreed to have TBW as part of their treatment. It may help to inform the mental health nursing practice. Introduction Many patients suffering from serious mental illness experience severe anxiety and those with psychosis often report the feeling of their bodies falling apart. While it is believed that these patients benefit from therapeutic body wraps (TBWs), the use of this adjunct therapy has rarely been studied in adult patients. Aims The aim of this study was to obtain descriptive statistics on the clinical, social-demographic and institutional reality of TBW therapy in Swiss public adult inpatient wards. Methods Retrospective data related to a cohort of 172 adult inpatients were retrieved from records of two public hospitals. Correlations between TBW and the prescriptions of lorazepam were explored. Results TBWs were primarily used for patients diagnosed with either schizophrenia, schizotypal, delusional and other non-mood psychotic disorders or mood disorders. Patients had, on average, four psychiatric hospitalizations, and in 30% of the cases, TBWs were offered during the first hospitalization. Moreover, TBWs were mostly practiced by nurses. Body wraps were potentially associated with a reduction in both anxiolytic and neuroleptic drugs. Discussion/Implication for practice Based on our results, TBW might contribute to the clinical management of anxiety by nurses. The efficacy of TWB regarding anxiety has yet to be investigated in a randomized controlled trial. © 2016 John Wiley & Sons Ltd.

Study on traditional Chinese medicine theory of lung being connected with large intestine.

PubMed

Liu, Ping; Wang, Ping; Tian, Daizhi; Liu, Junfeng; Chen, Gang; Liu, Songlin

2012-09-01

The theory of lung being connected with large intestine, which is a major topic in Traditional Chinese Medicine (TCM), has guided clinical practice for thousands of years in China. In this study, we analyzed the history, main contents, clinical application, and material basis of the theory, to attempt to improve the potential clinical significance of "lung being connected with large intestine" in China. The lung being connected with large intestine was first described in "Huang Di Nei Jing", and formed one of the basic theories of TCM. For thousands of years, the majority of TCM practitioners explored this theory continuously, leading to its development and use as an important theory in the guidance of TCM clinics In the last decade, researchers in the field of integrated TCM and Western medicine have studied clinical applications and biomedical mechanisms with experimental methods to explore the implications of the theory. With the further development of science and technology, research concerning the theory of lung being connected with large intestine will be greatly stimulated and contribute to the modernization of TCM.

DSM-5 pathological personality traits and the personality assessment inventory.

PubMed

Hopwood, Christopher J; Wright, Aidan G C; Krueger, Robert F; Schade, Nick; Markon, Kristian E; Morey, Leslie C

2013-06-01

Section 3 of the DSM-5 will include a pathological personality trait system rooted in the quantitative epistemology of personality and clinical psychology. This system has the potential to enhance the clinical utility of the diagnostic nosology by providing a means for the dimensional assessment of individuals with psychopathology. However, there is limited research on the associations of DSM-5 traits with common mental disorders and related clinical phenomena as measured by currently popular assessment instruments. The purpose of this article was to evaluate the convergence of the DSM-5 trait system with a well-validated broadband clinical instrument, the Personality Assessment Inventory (PAI). Bivariate correlations were examined and factor analytic methods were used to examine the degree to which the DSM-5 traits and PAI capture common variance in personality and mental health. In a student sample (N = 1,001), we found broad convergence between the DSM-5 traits and PAI, which could be organized effectively using five factors. The implications of these findings for using traits to address issues related to diagnostic co-occurrence and heterogeneity in routine clinical assessment are discussed.

Eating disorders with and without comorbid depression and anxiety: similarities and differences in a clinical sample of children and adolescents.

PubMed

Hughes, Elizabeth K; Goldschmidt, Andrea B; Labuschagne, Zandre; Loeb, Katharine L; Sawyer, Susan M; Le Grange, Daniel

2013-09-01

This study aimed to describe and compare the demographic and clinical characteristics of children and adolescents with an eating disorder (ED) and comorbid depression or anxiety. Data were drawn from intake assessments of children and adolescents at a specialist ED clinic. Demographic characteristics (e.g. age and gender) and clinical characteristics (e.g. body mass, binge eating and purging) were compared between 217 ED participants without comorbidity, 32 with comorbid anxiety, 86 with comorbid depression and 36 with comorbid anxiety and depression. The groups with comorbid depression had more complex and severe presentations compared with those with an ED and no comorbid disorder and those with comorbid anxiety alone, especially in regard to binge eating, purging, dietary restraint and weight/shape concerns. Depression and anxiety were differentially related to clinical characteristics of EDs. The findings have implications for understanding the relations between these disorders and their potential to impact outcome of ED treatments. Copyright © 2013 John Wiley & Sons, Ltd and Eating Disorders Association.

A Difficult Journey: Reflections on Driving and Driving Cessation From a Team of Clinical Researchers.

PubMed

Liddle, Jacki; Gustafsson, Louise; Mitchell, Geoffrey; Pachana, Nancy A

2017-02-01

Recognizing the clinical importance and safety and well-being implications for the population, a multidisciplinary team has been researching older drivers and driving cessation issues for more than 15 years. Using empirical approaches, the team has explored quality of life and participation outcomes related to driving and nondriving for older people and has developed interventions to improve outcomes after driving cessation. The team members represent occupational therapists, medical practitioners, and clinical and neuropsychologists. While building the evidence base for driving- and driving cessation-related clinical practice, the researchers have also had first-hand experiences of interruptions to their own or parents' driving; involvement of older family members in road crashes; and provision of support during family members' driving assessment and cessation. This has led to reflection on their understandings and re-evaluation and refocusing of their perspectives in driving cessation research. This work will share the narratives of the authors and note their developing perspectives and foci within research as well as their clinical practice. Personal reflections have indicated the far-reaching implications for older drivers and family members of involvement in road crashes: the potential for interruptions to driving as a time for support and future planning and the conflicting and difficult roles of family members within the driving cessation process. Overall the lived, personal experience of the authors has reinforced the complex nature of driving and changes to driving status for the driver and their support team and the need for further research and support. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Evaluation of energy in heated water vapor for the application of lung volume reduction in patients with severe emphysema.

PubMed

Henne, Erik; Kesten, Steven; Herth, Felix J F

2013-01-01

A method of achieving endoscopic lung volume reduction for emphysema has been developed that utilizes precise amounts of thermal energy in the form of water vapor to ablate lung tissue. This study evaluates the energy output and implications of the commercial InterVapor system and compares it to the clinical trial system. Two methods of evaluating the energy output of the vapor systems were used, a direct energy measurement and a quantification of resultant thermal profile in a lung model. Direct measurement of total energy and the component attributable to gas (vapor energy) was performed by condensing vapor in a water bath and measuring the temperature and mass changes. Infrared images of a lung model were taken after vapor delivery. The images were quantified to characterize the thermal profile. The total energy and vapor energy of the InterVapor system was measured at various dose levels and compared to the clinical trial system at a dose of 10.0 cal/g. An InterVapor dose of 8.5 cal/g was found to have the most similar vapor energy output with the smallest associated reduction in total energy. This was supported by characterization of the thermal profile in the lung model that demonstrated the profile of InterVapor at 8.5 cal/g to not exceed the profile of the clinical trial system. Considering both total energy and vapor energy is important during the development of clinical vapor applications. For InterVapor, a closer study of both energy types justified a reduced target vapor-dosing range for lung volume reduction. The clinical implication is a potential improvement for benefiting the risk profile. Copyright © 2013 S. Karger AG, Basel.

Patient, caregiver and clinician views on engagement in comparative effectiveness research.

PubMed

Forsythe, Laura P; Frank, Lori B; Workman, Thomas A; Hilliard, Tandrea; Harwell, Daniel; Fayish, Lauren

2017-05-01

Describe patient, caregiver and clinician views toward engagement as partners in health research. Online surveys of patients and caregivers managing rare (n = 560 patients, n = 609 caregivers) or chronic conditions (n = 762 patients, n = 776 caregivers) and practicing clinicians (n = 638). Over half of respondents were unfamiliar with the concept of partnering with researchers but most expressed interest in working in a research partnership. Potential facilitators endorsed were ensuring research is meaningful, applying results in an understandable way, and sharing results. Lack of time is a potential barrier. Clinicians were most interested in helping researchers decide on intervention comparisons and identifying implications for clinical practice. Patients, caregivers and clinicians are interested in research roles that emphasize usefulness and understandability of research.

Has NICE got it right? An international perspective considering the case of Technology Appraisal No. 98 by the National Institute for Health and Clinical Excellence (NICE).

PubMed

Schlander, Michael

2008-04-01

The National Institute for Health and Clinical Excellence (NICE) has been widely recognised as setting an international standard for high-quality health technology assessments (HTAs) including economic evaluation. A previous critical analysis of NICE Technology Appraisal No. 98 (TA98), evaluating methylphenidate, dexamphetamine and atomoxetine for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, revealed a number of issues, which must cast doubt on the robustness of the NICE approach when addressing a complex clinical decision problem. The exploration of potential underlying problems will be followed by a discussion of lessons for international healthcare policy-makers, and is intended to be an invitation to further debate and inquiry, not a presentation of definitive conclusions. Pertaining to the technology assessment report, potential problems were identified relating to an unnecessarily narrow scope, data search and selection strategy, the distinction between efficacy and effectiveness, data synthesis across studies and clinical effect measures, and limitations of the economic model. The appraisal process moderated the asserted 'clear conclusions' of the assessment but could not compensate for some of its gaps. It is suggested that key issues contributing to these problems may have included a separation of clinical and economic perspectives, a highly standardised reference case analysis that was followed schematically, the absence of an effective system for quality assurance of technology assessments, and transparency deficits of the economic evaluation. Further considerations for international policy-makers looking at NICE as a potential role model for HTAs are discussed, such as institutional context, the objectives of collectively financed healthcare and related value judgments, the reliance on QALYs as a universal and comprehensive measure of health benefits, the appropriate perspective for analysis, and process-related implications.

Eat, breathe, ROS: controlling stem cell fate through metabolism.

PubMed

Kubli, Dieter A; Sussman, Mark A

2017-05-01

Research reveals cardiac regeneration exists at levels previously deemed unattainable. Clinical trials using stem cells demonstrate promising cardiomyogenic and regenerative potential but insufficient contractile recovery. Incomplete understanding of the biology of administered cells likely contributes to inconsistent patient outcomes. Metabolism is a core component of many well-characterized stem cell types, and metabolic changes fundamentally alter stem cell fate from self-renewal to lineage commitment, and vice versa. However, the metabolism of stem cells currently studied for cardiac regeneration remains incompletely understood. Areas covered: Key metabolic features of stem cells are reviewed and unique stem cell metabolic characteristics are discussed. Metabolic changes altering stem cell fate are considered from quiescence and self-renewal to lineage commitment. Key metabolic concepts are applied toward examining cardiac regeneration through stem cell-based approaches, and clinical implications of current cell therapies are evaluated to identify potential areas of improvement. Expert commentary: The metabolism and biology of stem cells used for cardiac therapy remain poorly characterized. A growing appreciation for the fundamental relationship between stem cell functionality and metabolic phenotype is developing. Future studies unraveling links between cardiac stem cell metabolism and regenerative potential may considerably improve treatment strategies and therapeutic outcomes.

The Brøset Violence Checklist: clinical utility in a secure psychiatric intensive care setting.

PubMed

Clarke, D E; Brown, A-M; Griffith, P

2010-09-01

Violence towards health-care workers, especially in areas such as mental health/psychiatry, has become increasingly common, with nursing staff suggesting that a fear of violence from their patients may affect the quality of care they provide. Structured clinical tools have the potential to assist health-care providers in identifying patients who have the potential to become violent or aggressive. The Brøset Violence Checklist (BVC), a six-item instrument that uses the presence or absence of three patient characteristics and three patient behaviours to predict the potential for violence within a subsequent 24-h period, was trialled for 3 months on an 11-bed secure psychiatric intensive care unit. Despite the belief on the part of some nurses that decisions related to risk for violence and aggression rely heavily on intuition, there was widespread acceptance of the tool. During the trial, use of seclusion decreased suggesting that staff were able to intervene before seclusion was necessary. The tool has since been implemented as a routine part of patient care on two units in a 92-bed psychiatric centre. Five-year follow-up data and implications for practice are presented.

Eat, breathe, ROS: controlling stem cell fate through metabolism

PubMed Central

Kubli, Dieter A.; Sussman, Mark A.

2017-01-01

Introduction Research reveals cardiac regeneration exists at levels previously deemed unattainable. Clinical trials using stem cells demonstrate promising cardiomyogenic and regenerative potential but insufficient contractile recovery. Incomplete understanding of the biology of administered cells likely contributes to inconsistent patient outcomes. Metabolism is a core component of many well-characterized stem cell types, and metabolic changes fundamentally alter stem cell fate from self-renewal to lineage commitment, and vice versa. However, the metabolism of stem cells currently studied for cardiac regeneration remains incompletely understood. Areas covered Key metabolic features of stem cells are reviewed and unique stem cell metabolic characteristics are discussed. Metabolic changes altering stem cell fate are considered from quiescence and self-renewal to lineage commitment. Key metabolic concepts are applied toward examining cardiac regeneration through stem cell-based approaches, and clinical implications of current cell therapies are evaluated to identify potential areas of improvement. Expert commentary The metabolism and biology of stem cells used for cardiac therapy remain poorly characterized. A growing appreciation for the fundamental relationship between stem cell functionality and metabolic phenotype is developing. Future studies unraveling links between cardiac stem cell metabolism and regenerative potential may considerably improve treatment strategies and therapeutic outcomes. PMID:28406333

Helicopter Emergency Medical Services (HEMS) over-triage and the financial implications for major trauma centres in NSW, Australia

PubMed Central

2013-01-01

Background In NSW Australia, a formal trauma system including the use of helicopter emergency medical services (HEMS) has existed for over 20 years. Despite providing many advantages in NSW, HEMS patients are frequently over-triaged; leading to financial implications for major trauma centres that receive HEMS patients. The aim of this study was to investigate the financial implications of HEMS over-triage from the perspective of major trauma centres in NSW. Methods The study sample included all trauma patients transported via HEMS to 12 major trauma centres in NSW during the period: 1 July 2008 to 30 June 2009. Clinical data were gathered from individual hospital trauma registries and merged with financial information obtained from casemix units at respective hospitals. HEMS over-triage was estimated based on the local definition of minor to moderate trauma (ISS≤12) and hospital length of stay of less than 24 hrs. The actual treatment costs were determined and compared to state-wide peer group averages to obtain estimates of potential funding discrepancies. Results A total of 707 patients transported by HEMS were identified, including 72% pre-hospital (PH; n=507) and 28% inter-hospital (IH; n=200) transports. Over-triage was estimated at 51% for PH patients and 29% for IH patients. Compared to PH patients, IH patients were more costly to treat on average (IH: $42,604; PH: $25,162), however PH patients were more costly overall ($12,329,618 [PH]; $8,265,152 [IH]). When comparing actual treatment costs to peer group averages we found potential funding discrepancies ranging between 4% and 32% across patient groups. Using a sensitivity analysis, the potential funding discrepancy increased with increasing levels of over-triage. Conclusions HEMS patients are frequently over-triaged in NSW, leading to funding implications for major trauma centres. In general, HEMS patient treatment costs are higher than the peer group average and the potential funding discrepancy varies by injury severity and the type of transport performed. Although severely injured HEMS patients are more costly to treat, HEMS patients with minor injuries make up the majority of HEMS transports and have larger relative potential funding discrepancies. Future episode funding models need to account for the variability of trauma patients and the proportion of patients transported via HEMS. PMID:23815080

Helicopter emergency medical services (HEMS) over-triage and the financial implications for major trauma centres in NSW, Australia.

PubMed

Taylor, Colman B; Curtis, Kate; Jan, Stephen; Newcombe, Mark

2013-07-01

In NSW Australia, a formal trauma system including the use of helicopter emergency medical services (HEMS) has existed for over 20 years. Despite providing many advantages in NSW, HEMS patients are frequently over-triaged; leading to financial implications for major trauma centres that receive HEMS patients. The aim of this study was to investigate the financial implications of HEMS over-triage from the perspective of major trauma centres in NSW. The study sample included all trauma patients transported via HEMS to 12 major trauma centres in NSW during the period: 1 July 2008 to 30 June 2009. Clinical data were gathered from individual hospital trauma registries and merged with financial information obtained from casemix units at respective hospitals. HEMS over-triage was estimated based on the local definition of minor to moderate trauma (ISS≤12) and hospital length of stay of less than 24 hrs. The actual treatment costs were determined and compared to state-wide peer group averages to obtain estimates of potential funding discrepancies. A total of 707 patients transported by HEMS were identified, including 72% pre-hospital (PH; n=507) and 28% inter-hospital (IH; n=200) transports. Over-triage was estimated at 51% for PH patients and 29% for IH patients. Compared to PH patients, IH patients were more costly to treat on average (IH: $42,604; PH: $25,162), however PH patients were more costly overall ($12,329,618 [PH]; $8,265,152 [IH]). When comparing actual treatment costs to peer group averages we found potential funding discrepancies ranging between 4% and 32% across patient groups. Using a sensitivity analysis, the potential funding discrepancy increased with increasing levels of over-triage. HEMS patients are frequently over-triaged in NSW, leading to funding implications for major trauma centres. In general, HEMS patient treatment costs are higher than the peer group average and the potential funding discrepancy varies by injury severity and the type of transport performed. Although severely injured HEMS patients are more costly to treat, HEMS patients with minor injuries make up the majority of HEMS transports and have larger relative potential funding discrepancies. Future episode funding models need to account for the variability of trauma patients and the proportion of patients transported via HEMS.

A qualitative study on pharmacists’ perception on integrating pharmacists into private general practitioner’s clinics in Malaysia

PubMed Central

2017-01-01

Background: Private general practitioners in Malaysia largely operates as solo practices – prescribing and supplying medications to patients directly from their clinics, thus posing risk of medication-related problems to consumers. A pharmacy practice reform that integrates pharmacists into primary healthcare clinics can be a potential initiative to promote quality use of medication. This model of care is a novel approach in Malaysia and research in the local context is required, especially from the perspectives of pharmacists. Objective: To explore pharmacists’ views in integrating pharmacists into private GP clinics in Malaysia. Methods: A combination of purposive and snowballing sampling was used to recruit community and hospital pharmacists from urban areas in Malaysia to participate either in focus groups or semi-structured interviews. A total of 2 focus groups and 4 semi-structured interviews were conducted. Sessions were audio recorded, transcribed verbatim and thematically analysed using NVivo 10. Results: Four major themes were identified: (1) Limited potential to expand pharmacists’ roles, (2) Concerns about non-pharmacists dispensing medicines in private GP clinics, (3) Lack of trust from consumers and private GPs, (4) Cost implications. Participants felt that there was a limited role for pharmacists in private GP clinics. This was because the medication supply role is currently undertaken in private GP clinics without the need of pharmacists. The perceived lack of trust from consumers and private GPs towards pharmacists arises from the belief that healthcare is the GPs’ responsibility. This suggests that there is a need for increased public and GP awareness towards the capabilities of pharmacists’ in medication management. Participants were concerned about an increase in cost to private GP visits if pharmacists were to be integrated. Nevertheless, some participants perceived the integration as a means to reduce medical costs through improved quality use of medicines. Conclusion: Findings from the study provided a better understanding to help ascertain pharmacists’ views on their readiness and acceptance in a potential new model of practice. PMID:28943979

Promise of bitter melon (Momordica charantia) bioactives in cancer prevention and therapy

PubMed Central

Raina, Komal; Kumar, Dileep; Agarwal, Rajesh

2016-01-01

Recently, there is a paradigm shift that the whole food-derived components are not ‘idle bystanders’ but actively participate in modulating aberrant metabolic and signaling pathways in both healthy and diseased individuals. One such whole food from Cucurbitaceae family is ‘bitter melon’ (Momordica charantia, also called bitter gourd, balsam apple, etc.), which has gained an enormous attention in recent years as an alternative medicine in developed countries. The increased focus on bitter melon consumption could in part be due to several recent pre-clinical efficacy studies demonstrating bitter melon potential to target obesity/type II diabetes-associated metabolic aberrations as well as its pre-clinical anti-cancer efficacy against various malignancies. The bioassay-guided fractionations have also classified the bitter melon chemical constituents based on their anti-diabetic or cytotoxic effects. Thus, by definition, these bitter melon constituents are at cross roads on the bioactivity parameters; they either have selective efficacy for correcting metabolic aberrations or targeting cancer cells, or have beneficial effects in both conditions. However, given the vast, though dispersed, literature reports on the bioactivity and beneficial attributes of bitter melon constituents, a comprehensive review on the bitter melon components and the overlapping beneficial attributes is lacking; our review attempts to fulfill these unmet needs. Importantly, the recent realization that there are common risk factors associated with obesity/type II diabetes-associated metabolic aberrations and cancer, this timely review focuses on the dual efficacy of bitter melon against the risk factors associated with both diseases that could potentially impact the course of malignancy to advanced stages. Furthermore, this review also addresses a significant gap in our knowledge regarding the bitter melon drug-drug interactions which can be predicted from the available reports on bitter melon effects on metabolism enzymes and drug transporters. This has important implications, given that a large proportion of individuals, taking bitter melon based supplements/phytochemical extracts/food based home-remedies, are also likely to be taking conventional therapeutic drugs at the same time. Accordingly, the comprehensively reviewed information here could be prudently translated to the clinical implications associated with any potential concerns regarding bitter melon consumption by cancer patients. PMID:27452666

Promise of bitter melon (Momordica charantia) bioactives in cancer prevention and therapy.

PubMed

Raina, Komal; Kumar, Dileep; Agarwal, Rajesh

2016-10-01

Recently, there is a paradigm shift that the whole food-derived components are not 'idle bystanders' but actively participate in modulating aberrant metabolic and signaling pathways in both healthy and diseased individuals. One such whole food from Cucurbitaceae family is 'bitter melon' (Momordica charantia, also called bitter gourd, balsam apple, etc.), which has gained an enormous attention in recent years as an alternative medicine in developed countries. The increased focus on bitter melon consumption could in part be due to several recent pre-clinical efficacy studies demonstrating bitter melon potential to target obesity/type II diabetes-associated metabolic aberrations as well as its pre-clinical anti-cancer efficacy against various malignancies. The bioassay-guided fractionations have also classified the bitter melon chemical constituents based on their anti-diabetic or cytotoxic effects. Thus, by definition, these bitter melon constituents are at cross roads on the bioactivity parameters; they either have selective efficacy for correcting metabolic aberrations or targeting cancer cells, or have beneficial effects in both conditions. However, given the vast, though dispersed, literature reports on the bioactivity and beneficial attributes of bitter melon constituents, a comprehensive review on the bitter melon components and the overlapping beneficial attributes is lacking; our review attempts to fulfill these unmet needs. Importantly, the recent realization that there are common risk factors associated with obesity/type II diabetes-associated metabolic aberrations and cancer, this timely review focuses on the dual efficacy of bitter melon against the risk factors associated with both diseases that could potentially impact the course of malignancy to advanced stages. Furthermore, this review also addresses a significant gap in our knowledge regarding the bitter melon drug-drug interactions which can be predicted from the available reports on bitter melon effects on metabolism enzymes and drug transporters. This has important implications, given that a large proportion of individuals, taking bitter melon based supplements/phytochemical extracts/food based home-remedies, are also likely to be taking conventional therapeutic drugs at the same time. Accordingly, the comprehensively reviewed information here could be prudently translated to the clinical implications associated with any potential concerns regarding bitter melon consumption by cancer patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cornelia de Lange syndrome and molecular implications of the cohesin complex: Abstracts from the 7th biennial scientific and educational symposium 2016

PubMed Central

Kline, Antonie D.; Krantz, Ian D.; Deardorff, Matthew A.; Shirahige, Katsuhiko; Dorsett, Dale; Gerton, Jennifer L.; Wu, Meng; Mehta, Devanshi; Mills, Jason A.; Carrico, Cheri S.; Noon, Sarah; Herrera, Pamela S.; Horsfield, Julia A.; Bettale, Chiara; Morgan, Jeremy; Huisman, Sylvia A.; Moss, Jo; McCleery, Joseph; Grados, Marco; Hansen, Blake D.; Srivastava, Siddharth; Taylor-Snell, Emily; Kerr, Lynne M.; Katz, Olivia; Calof, Anne L.; Musio, Antonio; Egense, Alena; Haaland, Richard E.

2017-01-01

Cornelia de Lange Syndrome (CdLS) is due to mutations in the genes for the structural and regulatory proteins that make up the cohesin complex, and is considered a cohesinopathy disorder or, more recently, a transcriptomopathy. New phenotypes have been recognized in this expanding field. There are multiple clinical issues facing individuals with all forms of CdLS, particularly in the neurodevelopmental system, but also gastrointestinal, cardiac, and musculoskeletal. Aspects of developmental and cell biology have found common endpoints in the biology of the cohesin complex, with improved understanding of the mechanisms, easier diagnostic tests, and the possibility of potential therapeutics, all major clinical implications for the individual with CdLS. The following abstracts are the presentations from the 7th Cornelia de Lange Syndrome Scientific and Educational Symposium, June 22–23, 2016, in Orlando, FL, in conjunction with the Cornelia de Lange Syndrome Foundation National Meeting. In addition to the scientific and clinical discussions, there were talks related to practical aspects of behavior including autism, transitions, communication, access to medical care, and databases. At the end of the symposium, a panel was held, which included several parents, affected individuals and genetic counselors, and discussed the greatest challenges in life and how this information can assist in guiding future research. The Research Committee of the CdLS Foundation organizes this meeting, reviews, and accepts abstracts, and subsequently disseminates the information to the families through members of the Clinical Advisory Board and publications. AMA CME credits were provided by Greater Baltimore Medical Center, Baltimore, MD. PMID:28190301

Predictors and clinical implications of shivering during therapeutic normothermia.

PubMed

Badjatia, Neeraj; Kowalski, Robert G; Schmidt, J Michael; Voorhees, Marc E; Claassen, Jan; Ostapkovich, Noeleen D; Presciutti, Mary; Connolly, E Sander; Palestrant, David; Parra, Augusto; Mayer, Stephan A

2007-01-01

Shivering during induced normothermia (IN) remains a therapeutic limitation. We investigated potential risk factors and clinical implications of shivering during IN. Post hoc analysis was performed on 24 patients enrolled in a clinical trial of an automated surface cooling system to achieve IN. Hyponatremia was defined as serum levels <136 mmol/L and hypomagnesaemia as levels <1.5 mg/dL. Continuous heat energy transfer (kcal/h) was averaged hourly. Glasgow Coma Scale (GCS) scores were recorded every 2 h. Shivering status was documented hourly. Mixed effects modeling was used to determine clinical measures associated with shivering. Generalized estimating equation (GEE) models were used to compare baseline-adjusted repeated-measures GCS scores. About of 24 (39%) patients demonstrated shivering. Shivering was associated with men (67% vs. 21%, P = 0.03), hyponatremia (44% vs. 7%, P = 0.03), and hypomagnesaemia (56% vs. 7%, P = 0.02). The average kcal/h (158 +/- 645 kcal/h vs. 493 +/- 645 kcal/h, P = 0.03) was greater in shivering patients. Shivering was positively associated with increases in heart rate (P < 0.001), respiratory rate (P < 0.001), and kcal/h (P < 0.001). Non-shivering patients showed a greater increase from baseline GCS (GEE, P = 0.02) at 24 h. No differences in sedative doses or fever burden were noted between shiverers and non-shiverers. Men, hyponatremia, and hypomagnesaemia may predispose febrile patients treated with IN to shivering. Shivering dramatically increases the amount of heat transfer required to maintain normothermia, and may be associated with adverse effects on level of consciousness.

Major depressive disorder in DSM-5: implications for clinical practice and research of changes from DSM-IV.

PubMed

Uher, Rudolf; Payne, Jennifer L; Pavlova, Barbara; Perlis, Roy H

2014-06-01

The changes in diagnostic criteria for major depressive disorder (MDD) from the fourth to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) may appear small but have important consequences for how the diagnosis is used. In DSM-5, MDD is part of the new "Depressive disorders" section, which is separate from "Bipolar disorders", marking a division in what had been known as "Mood disorders". A small wording change has expanded the core mood criterion to include hopelessness, potentially broadening the diagnosis. The replacement of an operationalized bereavement exclusion with a call for clinical judgment in distinguishing normal reactions to significant loss from a disorder in need of clinical attention makes the diagnosis less objective and complicates investigations of the relationship between adversity and depression. A new persistent depressive disorder category is intended to encompass both dysthymia and chronic depression, but its relationship to MDD is ambiguous with conflicting statements on whether the two diagnoses should be concurrent if both sets of criteria are fulfilled. Clarification is also needed on whether MDD can be concurrent with the new broad "other specified bipolar and related disorders". New specifiers of MDD "with anxious distress" and "with mixed features" allow characterization of additional symptoms. The specifier "with perinatal onset" expands on the DSM-IV "postnatal onset" to include onset during pregnancy. We review the changes in MDD definition, provide guidance on their implementation and discuss their implications for clinical practice and research. © 2013 Wiley Periodicals, Inc.

Utility of the Electrocardiogram in Drug Overdose and Poisoning: Theoretical Considerations and Clinical Implications

PubMed Central

Yates, Christopher; Manini, Alex F

2012-01-01

The ECG is a rapidly available clinical tool that can help clinicians manage poisoned patients. Specific myocardial effects of cardiotoxic drugs have well-described electrocardiographic manifestations. In the practice of clinical toxicology, classic ECG changes may hint at blockade of ion channels, alterations of adrenergic tone, or dysfunctional metabolic activity of the myocardium. This review will offer a structured approach to ECG interpretation in poisoned patients with a focus on clinical implications and ECG-based management recommendations in the initial evaluation of patients with acute cardiotoxicity. PMID:22708912

Supernatural impotence: historical review with anthropological and clinical implications.

PubMed

Margolin, J; Witztum, E

1989-12-01

The historical and cultural background of the belief in supernatural impotence is presented, emphasizing its possible implications for clinical practice. A brief historical survey of the concept in Judaism and Christianity is followed by a short anthropological survey of supernatural impotence in different ethnic subcultures in Israel. A case demonstration exemplifies the connection between understanding the patient's cultural background and beliefs and the clinical competence of the therapist. The relationship between the clinical-therapeutic process in psychiatric practice and knowledge of the patient's cultural background and beliefs is stressed.

Complement activation and choriocapillaris loss in early AMD: Implications for pathophysiology and therapy

PubMed Central

Whitmore, S.Scott; Sohn, Elliott H.; Chirco, Kathleen R.; Drack, Arlene V.; Stone, Edwin M.; Tucker, Budd A.; Mullins, Robert F.

2015-01-01

Age-related macular degeneration (AMD) is a common and devastating disease that can result in severe visual dysfunction. Over the last decade, great progress has been made in identifying genetic variants that contribute to AMD, many of which lie in genes involved in the complement cascade. In this review we discuss the significance of complement activation in AMD, particularly with respect to the formation of the membrane attack complex in the aging choriocapillaris. We review the clinical, histological and biochemical data that indicate that vascular loss in the choroid occurs very early in the pathogenesis of AMD, and discuss the potential impact of vascular dropout on the retinal pigment epithelium, Bruch's membrane and the photoreceptor cells. Finally, we present a hypothesis for the pathogenesis of early AMD and consider the implications of this model on the development of new therapies. PMID:25486088

Complement activation and choriocapillaris loss in early AMD: implications for pathophysiology and therapy.

PubMed

Whitmore, S Scott; Sohn, Elliott H; Chirco, Kathleen R; Drack, Arlene V; Stone, Edwin M; Tucker, Budd A; Mullins, Robert F

2015-03-01

Age-related macular degeneration (AMD) is a common and devastating disease that can result in severe visual dysfunction. Over the last decade, great progress has been made in identifying genetic variants that contribute to AMD, many of which lie in genes involved in the complement cascade. In this review we discuss the significance of complement activation in AMD, particularly with respect to the formation of the membrane attack complex in the aging choriocapillaris. We review the clinical, histological and biochemical data that indicate that vascular loss in the choroid occurs very early in the pathogenesis of AMD, and discuss the potential impact of vascular dropout on the retinal pigment epithelium, Bruch's membrane and the photoreceptor cells. Finally, we present a hypothesis for the pathogenesis of early AMD and consider the implications of this model on the development of new therapies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Anaphylaxis in a food allergy outpatient department: one-year review.

PubMed

Fernandes, R A; Regateiro, F; Pereira, C; Faria, E; Pita, J; Todo-Bom, A; Carrapatoso, I

2018-03-01

Background. Anaphylaxis is an acute, potentially fatal, multi-organ allergic reac-tion. Our aim was to characterize the population with food induced anaphylaxis followed over a one-year period. Methods. Retrospective analysis of clinical files of patients with food anaphylaxis observed in our food allergy consultation during 2016. Results. Sixty-two patients were included. In the pediatric group, the implicated allergens were cow's milk, egg and fish and in the adults' group, the commonest allergens were nuts and wheat. Allergy to shrimp affected equally children and adults. The most frequent symptoms were urticaria (85.5%), angioedema (64.5%) and dyspnea (62.9%). Cofactors were present in 32.6% of patients, mainly exercise. Asthma and/or rhinitis were the most frequent comorbidities. Conclusion. In accordance to other studies, milk and egg were the most implicated allergens in children. Anaphylaxis in adults reflects the Mediterranean sensitization pattern. Exercise was the most relevant cofactor.

The Neurobiology of "Food Addiction" and Its Implications for Obesity Treatment and Policy.

PubMed

Carter, Adrian; Hendrikse, Joshua; Lee, Natalia; Yücel, Murat; Verdejo-Garcia, Antonio; Andrews, Zane B.; Hall, Wayne

2016-07-17

There is a growing view that certain foods, particularly those high in refined sugars and fats, are addictive and that some forms of obesity can usefully be treated as a food addiction. This perspective is supported by a growing body of neuroscience research demonstrating that the chronic consumption of energy-dense foods causes changes in the brain's reward pathway that are central to the development and maintenance of drug addiction. Obese and overweight individuals also display patterns of eating behavior that resemble the ways in which addicted individuals consume drugs. We critically review the evidence that some forms of obesity or overeating could be considered a food addiction and argue that the use of food addiction as a diagnostic category is premature. We also examine some of the potential positive and negative clinical, social, and public policy implications of describing obesity as a food addiction that require further investigation.

The Legal Landscape of Concussion: Implications for Sports Medicine Providers.

PubMed

Albano, Andrew W; Senter, Carlin; Adler, Richard H; Herring, Stanley A; Asif, Irfan M

2016-09-01

Concussion legislation has been enacted in all 50 of the United States, aiming to prevent mild traumatic brain injuries and the potential long-term sequelae of these injuries in youth athletics. Sports medicine providers, in addressing this major public health concern, are tasked with adhering to the established standards of medical care while also considering the legal implications. The PubMed (2011-2016) database was searched using the following search terms: concussion, sports concussion, legislation, and concussion legislation. References from consensus statements, review articles, and book chapters were also utilized. Clinical review. Level 4. The Lystedt law and its progeny have increased awareness of the signs and symptoms of sports concussion, but adherence to state legislation can pose some challenges. The presence of concussion legislation places a responsibility on the sports medicine provider to have a firm understanding of the legality of concussion management in the state(s) in which they practice. © 2016 The Author(s).

Co-Occurring Disorders in Substance Abuse Treatment: Issues and Prospects

PubMed Central

Flynn, Patrick M.; Brown, Barry S.

2008-01-01

This paper explores the epidemiology of co-occurring disorders with an emphasis on the implications of study findings for the functioning and potential of substance abuse treatment. Severity of disorder is discussed as an issue that may have particular significance for the selection of specialized as opposed to traditional substance abuse treatment forms. Exploration is made, as well, of the resources currently available to substance abuse treatment, especially the human resources available, and the implications of resource availability for undertaking initiatives specific to co-occurring disorder. Findings from standard and enhanced treatment for comorbid individuals are examined in an effort to clarify areas of need for specialized and typical treatment personnel. Issues are raised for consideration by the clinical research and treatment provider communities in terms of assessment and diagnosis, manpower and training, and response to the challenge of relapse in this population. PMID:17574791

‘Schizophrenia is a dirty word’: service users’ experiences of receiving a diagnosis of schizophrenia

PubMed Central

Howe, Lorna; Tickle, Anna; Brown, Ian

2014-01-01

Aims and method To explore service users’ experiences of receiving a diagnosis of schizophrenia and the stigma associated with the diagnostic label. Seven participants were interviewed about their perceptions of these experiences. Interviews were analysed using interpretative phenomenological analysis. Results Five superordinate themes resulted from the analysis: (1) avoidance of the diagnosis of schizophrenia; (2) stigma and diagnostic labels; (3) lack of understanding of schizophrenia; (4) managing stigma to maintain normality; (5) being ‘schizophrenic’. These, together with their subthemes, highlighted avoidance of the term schizophrenia by participants and use of alternative terms by professionals, which limited opportunities for understanding the label and challenging associated stigma. Participants strived to maintain normality despite potential stigma. Clinical implications There is a need to address the process of giving a diagnosis as a phenomenon of consequence within its own terms. Implications relate to how professionals deliver and discuss the diagnosis of schizophrenia. PMID:25237536

E-Cigarettes and Smoking Cessation: A Primer for Oncology Clinicians.

PubMed

Zborovskaya, Yanina

2017-02-01

Electronic cigarettes 
(e-cigarettes) are a psychosocial phenomenon of the 21st century with serious implications to public and individual health. The significant increase of their popularity and use has raised concerns in the healthcare community regarding their potential benefits and harm, particularly their use as a smoking cessation methodology. Current knowledge is presented about e-cigarettes, including the clinical implications of their use, and associated controversies are analyzed. In addition, practice recommendations and communication guidance are provided. An integrative review was performed. The long-term effect of e-cigarettes on individual and public health is unknown. Evidence from short-term studies, although limited, shows that e-cigarette use is less harmful than smoking. However, the evidence does not support the use of e-cigarettes as a smoking cessation methodology. Such recommendation remains a judgment call for the clinician based on each individual case.

Immunological dysregulation in multiple myeloma microenvironment.

PubMed

Romano, Alessandra; Conticello, Concetta; Cavalli, Maide; Vetro, Calogero; La Fauci, Alessia; Parrinello, Nunziatina Laura; Di Raimondo, Francesco

2014-01-01

Multiple Myeloma (MM) is a systemic hematologic disease due to uncontrolled proliferation of monoclonal plasma cells (PC) in bone marrow (BM). Emerging in other solid and liquid cancers, the host immune system and the microenvironment have a pivotal role for PC growth, proliferation, survival, migration, and resistance to drugs and are responsible for some clinical manifestations of MM. In MM, microenvironment is represented by the cellular component of a normal bone marrow together with extracellular matrix proteins, adhesion molecules, cytokines, and growth factors produced by both stromal cells and PC themselves. All these components are able to protect PC from cytotoxic effect of chemo- and radiotherapy. This review is focused on the role of immunome to sustain MM progression, the emerging role of myeloid derived suppressor cells, and their potential clinical implications as novel therapeutic target.

[Foetal therapy for Down syndrome: a pro-active ethical reflection].

PubMed

de Wert, G M W R; Dondorp, W J

2016-01-01

Prenatal screening for Down syndrome has to date focused on facilitating the informed choice to continue or not with a pregnancy. The non-invasive prenatal test (NIPT) for Down syndrome does potentially offer the option to apply foetal neurocognitive therapy for Down syndrome (FTDS). Current research in animal models looks promising and therefore a proactive ethical reflection in relation to clinical trials is urgently needed. This discussion includes an exploration of the ethical aspects of FTDS. There seem to be no convincing a priori objections on the basis of the social model of disability. Arguments in terms of (respect for) autonomy, wellbeing and justice seem to in principle support such therapy. Still, both the conditions for sound clinical trials and the implications of possible effective therapy for current prenatal screening need further scrutiny.

Gene therapy in dentistry: tool of genetic engineering. Revisited.

PubMed

Gupta, Khushboo; Singh, Saurabh; Garg, Kavita Nitish

2015-03-01

Advances in biotechnology have brought gene therapy to the forefront of medical research. The concept of transferring genes to tissues for clinical applications has been discussed nearly half a century, but the ability to manipulate genetic material via recombinant DNA technology has brought this goal to reality. The feasibility of gene transfer was first demonstrated using tumour viruses. This led to development of viral and nonviral methods for the genetic modification of somatic cells. Applications of gene therapy to dental and oral problems illustrate the potential impact of this technology on dentistry. Preclinical trial results regarding the same have been very promising. In this review we will discuss methods, vectors involved, clinical implication in dentistry and scientific issues associated with gene therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

NMDA receptor as a newly identified member of the metabotropic glutamate receptor family: clinical implications for neurodegenerative diseases.

PubMed

Chung, ChiHye

2013-08-01

Recent reports have proposed a novel function for the N-methyl-D-aspartate (NMDA) receptor (NMDAR), a well-known excitatory, ionotropic receptor. A series of observations employing pharmacological techniques has proposed that upon ligand binding, this ionotropic receptor can actually function via signaling cascades independent of traditional ionotropic action. Moreover, the "metabotropic" action of NMDARs is suggested to mediate a form of synaptic plasticity, namely long-term synaptic depression (LTD), which shares cellular mechanisms with the synaptic deficits observed in Alzheimer's disease. Given that a growing body of clinical and preclinical evidence strongly recommends NMDAR antagonists for their therapeutic potentials and advantages in a variety of diseases, further investigation into their molecular and cellular mechanisms is required to better understand the "metabotropic" action of NMDARs.

Adverse effects of anticancer agents that target the VEGF pathway.

PubMed

Chen, Helen X; Cleck, Jessica N

2009-08-01

Antiangiogenesis agents that target the VEGF/VEGF receptor pathway have become an important part of standard therapy in multiple cancer indications. With expanded clinical experience with this class of agents has come the increasing recognition of the diverse adverse effects related to disturbance of VEGF-dependent physiological functions and homeostasis in the cardiovascular and renal systems, as well as wound healing and tissue repair. Although most adverse effects of VEGF inhibitors are modest and manageable, some are associated with serious and life-threatening consequences, particularly in high-risk patients and in certain clinical settings. This Review examines the toxicity profiles of anti-VEGF antibodies and small-molecule inhibitors. The potential mechanisms of the adverse effects, risk factors, and the implications for selection of patients and management are discussed.

Writing a case report: polishing a gem?

PubMed

Papanas, N; Lazarides, M K

2008-08-01

Case reports describe patient cases which are of particular interest due to their novelty and their potential message for clinical practice. While there are several types of case reports, originality and clinical implications constitute the main virtues by which case reports are judged. Defining the educational message and choosing the right audience are vital steps in the process of writing. Generally, a case report is structured, its main components being the abstract, the introduction, the case description and the discussion. Guidelines and tips for writing case reports are not enough for making a successful author, but they help, especially less experienced doctors, to exercise and improve their writing. If properly prepared, case reports can still communicate new observations in an interesting and pleasant way, thereby enriching our knowledge, even in the era of evidence-based medicine.

[Two cases of typhoid fever with reduced susceptibility to fluoroquinolones].

PubMed

Adachi, T; Masuda, G; Imamura, A; Ajisawa, A; Negishi, M; Takayama, N; Takinaga, K; Takano, S

2001-01-01

Two separate febrile Indian patients who reside in Japan and had recently returned from their country were diagnosed as suffering from typhoid fever. Fluoroquinolone therapy was clinically ineffective and the addition of a third-generation cephalosporin was required in each case. Each strain of Salmonella Typhi was resistant to nalidixic acid in vitro and also showed higher minimal inhibitory concentration to other quinolones than usual susceptible strains. Similar cases of typhoid fever responding poorly to quinolone treatment have been observed in the Indian subcontinent, south-east Asia and central Asia since the early 1990s, and potential spread by travelers into Japan is of serious concern. Although quinolones still remain the drugs of choice for treatment of typhoid fever, physicians should be aware of the possibility and implications of clinical treatment failure.

Herpes Simplex Virus Infection in a University Health Population: Clinical Manifestations, Epidemiology, and Implications

ERIC Educational Resources Information Center

Horowitz, Robert; Aierstuck, Sara; Williams, Elizabeth A.; Melby, Bernette

2010-01-01

Objective: The authors described clinical presentations of oral and genital herpes simplex virus (HSV) infections in a university health population and implications of these findings. Participants and Methods: Using a standardized data collection tool, 215 records of patients with symptomatic culture-positive HSV infections were reviewed. Results:…

Cancer Stem Cells (CSCs) and Mechanisms of Their Regulation: Implications for Cancer Therapy

PubMed Central

Bao, Bin; Ahmad, Aamir; Azmi, Asfar S.; Ali, Shadan; Sarkar, Fazlul H.

2013-01-01

The identification of small subpopulations of cancer stem cells (CSCs) from blood mononuclear cells in human acute myeloid leukemia (AML) in 1997 was the landmark observation for recognizing the potential role of CSCs in tumor aggressiveness. Two critical properties contribute to the functional role of CSCs in the establishment and recurrence of cancerous tumors: their self-renewal capacity and their potential to differentiate into unlimited heterogeneous populations of cancer cells. These findings suggest that CSCs may represent novel therapeutic targets for the treatment and/or prevention of tumor progression as they appear to be involved in cell migration, invasion, metastasis, and treatment resistance, all of which lead to poor clinical outcomes. The identification of CSC-specific markers, the isolation and characterization of CSCs from malignant tissues, and targeting strategies for the destruction of CSCs provides a novel opportunity for cancer research. Described in this overview is the potential implication of several common CSC markers in the identification of CSC subpopulation restricted to common malignant diseases e.g., leukemia, breast, prostate, pancreatic and lung cancers. The role of microRNAs (miRNAs) in the regulation of CSC function is also discussed, as are several methods commonly used in CSC research. The potential role of the anti-diabetic drug metformin that has been shown to have effects on CSCs, and known function as an anti-tumor agent, provides an example of this new class of chemotherapeutics. PMID:23744710

Inflammatory cells implicated in neoplasia development in idiopathic inflammatory bowel disease.

PubMed

Hashash, Jana G; Hartman, Douglas J

2017-11-10

The inflammatory mechanisms that lead to the clinical symptoms that are grouped under the term inflammatory bowel disease have not been fully characterized. Although a specific mechanism has not been identified, inflammatory bowel disease is believed to be related to an inability by the immune system to shut active inflammation within the intestine. Many contributing factors have been implicated in the disease process. Based on population studies, patients with inflammatory bowel disease have an increased risk for neoplastic development. Although no specific immune cell has been implicated in neoplastic development within this patient population, several immune cells have been implicated as possible etiologies in inflammatory bowel disease. In this review, we will review the clinical evidence about the risk for neoplastic development in inflammatory bowel disease and the current clinical guidelines to survey this patient population. We will also review the pathologic assessment of inflammation within this patient population as well the underlying immune cells and cytokines that have been implicated in the etiology of inflammatory bowel disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Framing the research agenda for sickle cell trait: building on the current understanding of clinical events and their potential implications

PubMed Central

Goldsmith, Jonathan C.; Bonham, Vence L.; Joiner, Clinton H.; Kato, Gregory J.; Noonan, Allan S.; Steinberg, Martin H.

2012-01-01

Sickle Cell Trait (HbAS), the heterozygous state for the sickle hemoglobin beta globin gene is carried by as many as 100 million individuals including up to 25% of the population in some regions of the world (World Health Organization, Provisional agenda item 4.8, EB117/34 (22 December 2005) or World Health Organization, Provisional agenda item 11.4 (24 April 2006)). Persons with HbAS have some resistance to falciparum malaria infection in early childhood (Piel FB, Patil AP, Howes RE, et al., Nat Commun 2010;1104:1–7 and Aidoo M, Terlouw DJ, Kolczak M, et al., Lancet 2002;359:1311–1312) and as a result individuals with HbAS living in malarial endemic regions of Africa have a survival advantage over individuals with HbAA. Reports from the US emphasize possible health risks for individuals with HbAS including increased incidence of renal failure and malignancy, thromboembolic disorders, splenic infarction as a high altitude complication, and exercise-related sudden death. The National Heart, Lung, and Blood Institute, National Institutes of Health convened a workshop in Bethesda, Maryland on June 3–4, 2010, Framing the Research Agenda for Sickle Cell Trait, to review the clinical manifestations of HbAS, discuss the exercise-related sudden death reports in HbAS, and examine the public health, societal, and ethical implications of policies regarding HbAS. The goal of the workshop was to identify potential research questions to address knowledge gaps. PMID:22307997

Less travelled roads in clinical immunology and allergy: drug reactions and the environmental influence.

PubMed

Selmi, Carlo; Crotti, Chiara; Meroni, Pier Luigi

2013-08-01

Allergy and clinical immunology are examples of areas of knowledge in which working hypotheses are dominant over mechanistic understanding. As such, sometimes scientific efforts follow major streams and overlook some epidemiologically prevalent conditions that thus become underestimated by the research community. For this reason, we welcome the present issue of Clinical Reviews in Allergy and Immunology that is dedicated to uncommon themes in clinical immunology and allergy. First, comprehensive discussions are provided for allergy phenomena of large potential impact in clinical practice such as reactions to cephalosporins or aspirin-induced asthma and in everyday life such as allergies to food additives or legumes. Further, the issue addresses other uncommon themes such as urticaria and angioedema, cercarial dermatitis, or late-onset inflammation to soft tissue fillers. Last, there will be discussion on transversal issues such as olfactory defects in autoimmunity, interleukin 1 beta pathway, and the search for new serological markers in chronic inflammation. As a result, we are convinced that this issue will be of help to clinicians involved in internal medicine as well as to allergists and clinical immunologists. More importantly, we are convinced that these discussions will be of interest also to basic scientists for the numerous translational implications.

Tendon Tissue Engineering: Progress, Challenges, and Translation to the Clinic

PubMed Central

Shearn, Jason T.; Kinneberg, Kirsten R.C.; Dyment, Nathaniel A.; Galloway, Marc T.; Kenter, Keith; Wylie, Christopher; Butler, David L.

2013-01-01

The tissue engineering field has made great strides in understanding how different aspects of tissue engineered constructs (TECs) and the culture process affect final tendon repair. However, there remain significant challenges in developing strategies that will lead to a clinically effective and commercially successful product. In an effort to increase repair quality, a better understanding of normal development, and how it differs from adult tendon healing, may provide strategies to improve tissue engineering. As tendon tissue engineering continues to improve, the field needs to employ more clinically relevant models of tendon injury such as degenerative tendons. We need to translate successes to larger animal models to begin exploring the clinical implications of our treatments. By advancing the models used to validate our TECs, we can help convince our toughest customer, the surgeon, that our products will be clinically efficacious. As we address these challenges in musculoskeletal tissue engineering, the field still needs to address the commercialization of products developed in the laboratory. TEC commercialization faces numerous challenges because each injury and patient is unique. This review aims to provide tissue engineers with a summary of important issues related to engineering tendon repairs and potential strategies for producing clinically successful products. PMID:21625053

Associations of plasma leptin to clinical manifestations in reproductive aged female patients with panic disorder.

PubMed

Masdrakis, Vasilios G; Papageorgiou, Charalambos; Markianos, Manolis

2017-09-01

Preclinical studies suggest the implication of the adipocyte hormone leptin in anxiety and fear processes. We explored for potential differences regarding plasma leptin, cortisol and the ratio leptin/Body Mass Index (BMI) between 27 medication-free female patients with Panic Disorder (PD) and 42 age-matched female controls, and for potential associations between plasma leptin and psychometric evaluations including number of panic attacks during last week, Clinical Global Impression-Severity of Illness (CGI-S) and Symptoms Checklist-90-Revised (SCL-90-R). Cortisol levels showed no differences between patients and controls, or correlations to leptin or to any clinical features. Both groups demonstrated a strong positive correlation between leptin and BMI and similar leptin and leptin/BMI, despite patients' lower BMI. However, patients -but not controls- demonstrated significant negative correlations of leptin to the 'somatization', 'anxiety', and 'phobic anxiety' SCL-90-R subscales. Moreover, there was a significant negative correlation of leptin and of leptin/BMI ratio to the number of panic attacks during last week, while higher CGI-S was associated with lower leptin/BMI ratio. Our results, limited to PD female patients, suggest that lower leptin serum levels are significantly associated with greater severity of psychopathological manifestations, including number of panic attacks, symptoms of somatization, anxiety and phobic anxiety and overall clinical presentation. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Signaling intermediates (MAPK and PI3K) as therapeutic targets in NSCLC.

PubMed

Ciuffreda, Ludovica; Incani, Ursula Cesta; Steelman, Linda S; Abrams, Stephen L; Falcone, Italia; Curatolo, Anais Del; Chappell, William H; Franklin, Richard A; Vari, Sabrina; Cognetti, Francesco; McCubrey, James A; Milella, Michele

2014-01-01

The RAS/RAF/MEK/ ERK and the PI3K/AKT/mTOR pathways govern fundamental physiological processes, such as cell proliferation, differentiation, metabolism, cytoskeleton reorganization and cell death and survival. Constitutive activation of these signal transduction pathways is a required hallmark of cancer and dysregulation, on either genetic or epigenetic grounds, of these pathways has been implicated in the initiation, progression and metastastic spread of lung cances. Targeting components of the MAPK and PI3K cascades is thus an attractive strategy in the development of novel therapeutic approaches to treat lung cancer, although the use of single pathway inhibitors has met with limited clinical success so far. Indeed, the presence of intra- and inter-pathway compensatory loops that re-activate the very same cascade, either upstream or downstream the point of pharmacological blockade, or activate the alternate pathway following the blockade of one signaling cascade has been demonstrated, potentially driving preclinical (and possibly clinical) resistance. Therefore, the blockade of both pathways with combinations of signaling inhibitors might result in a more efficient anti-tumor effect, and thus potentially overcome and/or delay clinical resistance, as compared with single agent. The current review aims at summarizing the current status of preclinical and clinical research with regard to pathway crosstalks between the MAPK and PI3K cascades in NSCLC and the rationale for combined therapeutic pathway targeting.

Drug-drug interactions involving lysosomes: mechanisms and potential clinical implications.

PubMed

Logan, Randall; Funk, Ryan S; Axcell, Erick; Krise, Jeffrey P

2012-08-01

Many commercially available, weakly basic drugs have been shown to be lysosomotropic, meaning they are subject to extensive sequestration in lysosomes through an ion trapping-type mechanism. The extent of lysosomal trapping of a drug is an important therapeutic consideration because it can influence both activity and pharmacokinetic disposition. The administration of certain drugs can alter lysosomes such that their accumulation capacity for co-administered and/or secondarily administered drugs is altered. In this review the authors explore what is known regarding the mechanistic basis for drug-drug interactions involving lysosomes. Specifically, the authors address the influence of drugs on lysosomal pH, volume and lipid processing. Many drugs are known to extensively accumulate in lysosomes and significantly alter their structure and function; however, the therapeutic and toxicological implications of this remain controversial. The authors propose that drug-drug interactions involving lysosomes represent an important potential source of variability in drug activity and pharmacokinetics. Most evaluations of drug-drug interactions involving lysosomes have been performed in cultured cells and isolated tissues. More comprehensive in vivo evaluations are needed to fully explore the impact of this drug-drug interaction pathway on therapeutic outcomes.

Measuring what matters: does 'objectivity' mean good science?

PubMed

Kayes, Nicola M; McPherson, Kathryn M

2010-01-01

While the limitations of self-report measures are clearly acknowledged, less apparent is attention to the potential limitations of their 'objective' counterparts leading to the assumption that objectivity results in more robust and scientifically valid measurement tools. This article aims to: (1) test this assumption; (2) consider the implications of advocating for a measure on the basis of its objectivity; (3) propose an alternative approach to measure selection. A critical evaluation of one 'objective' measure highlights a number of potential limitations suggesting that the apparent willingness to adopt 'objective' measures with little questioning may be misguided. The possible implications of this are discussed and include a risk to the advancement of, and capacity for, knowledge in rehabilitation; or worse, of making clinical decisions based on erroneous conclusions. Characterising a measure on the basis of objectivity (or not) assumes an overly simplistic dichotomy that is unhelpful and perhaps misleading. We argue that assessing whether a measure is fit for purpose and makes mathematical sense is the key consideration. Indeed, in some cases, using both an 'objective' measure and a subjective rating scale may be appropriate and the only way of truly capturing the phenomenon of interest.

Synergistic potentiation of D-fraction with vitamin C as possible alternative approach for cancer therapy.

PubMed

Konno, Sensuke

2009-07-30

Maitake D-fraction or PDF is the bioactive extract of maitake mushroom (Grifola frondosa) and its active constituent is the protein-bound polysaccharide (proteoglucan), or more specifically known as beta-glucan. PDF has been extensively studied and a number of its medicinal potentials/properties have been unveiled and demonstrated. Those include various physiological benefits ranging from immunomodulatory and antitumor activities to treatment for hypertension, diabetes, hypercholesterolemia, viral infections (hepatitis B and human immunodeficiency virus), and obesity. Particularly, two major biological activities of PDF, immunomodulatory and antitumor activities, have been the main target for scientific and clinical research. To demonstrate and confirm such biological activities, numerous studies have been performed in vitro and in vivo or in clinical settings. These studies showed that PDF was indeed capable of modulating immunologic and hematologic parameters, inhibiting or regressing the cancer cell growth, and even improving quality of life of cancer patients. Synergistic potentiation of PDF with vitamin C demonstrated in vitro is rather interesting and may have clinical implication, because such combination therapy appears to help improve the efficacy of currently ongoing cancer therapies. Recently, intravenous administration of vitamin C has been often used to increase its physiological concentration and this useful procedure may further make this combination therapy feasible. Therefore, PDF may have great potential, either being used solely or combined with other agents, for cancer therapy. Such relevant and detailed studies will be described and discussed herein with a special focus on the combination of PDF and vitamin C as a viable therapeutic option.

Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory

PubMed Central

Heisler, Jillian M.; O’Connor, Jason C.

2015-01-01

Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. PMID:26130057

The Role of Exercise in Cardiac Aging: From Physiology to Molecular Mechanisms

PubMed Central

Roh, Jason; Rhee, James; Chaudhari, Vinita; Rosenzweig, Anthony

2015-01-01

Aging induces structural and functional changes in the heart that are associated with increased risk of cardiovascular disease and impaired functional capacity in the elderly. Exercise is a diagnostic and therapeutic tool, with the potential to provide insights into clinical diagnosis and prognosis, as well as the molecular mechanisms by which aging influences cardiac physiology and function. In this review, we first provide an overview of how aging impacts the cardiac response to exercise and the implications this has for functional capacity in older adults. We then review the underlying molecular mechanisms by which cardiac aging contributes to exercise intolerance, and conversely how exercise training can potentially modulate aging phenotypes in the heart. Finally, we highlight the potential use of these exercise models to complement models of disease in efforts to uncover new therapeutic targets to prevent or treat heart disease in the aging population. PMID:26838314

The Role of Exercise in Cardiac Aging: From Physiology to Molecular Mechanisms.

PubMed

Roh, Jason; Rhee, James; Chaudhari, Vinita; Rosenzweig, Anthony

2016-01-22

Aging induces structural and functional changes in the heart that are associated with increased risk of cardiovascular disease and impaired functional capacity in the elderly. Exercise is a diagnostic and therapeutic tool, with the potential to provide insights into clinical diagnosis and prognosis, as well as the molecular mechanisms by which aging influences cardiac physiology and function. In this review, we first provide an overview of how aging impacts the cardiac response to exercise, and the implications this has for functional capacity in older adults. We then review the underlying molecular mechanisms by which cardiac aging contributes to exercise intolerance, and conversely how exercise training can potentially modulate aging phenotypes in the heart. Finally, we highlight the potential use of these exercise models to complement models of disease in efforts to uncover new therapeutic targets to prevent or treat heart disease in the aging population. © 2016 American Heart Association, Inc.

Teaching clinical reasoning to medical students.

PubMed

Gay, Simon; Bartlett, Maggie; McKinley, Robert

2013-10-01

Keele Medical School's new curriculum includes a 5-week course to extend medical students' consultation skills beyond those historically required for competent inductive diagnosis. Clinical reasoning is a core skill for the practice of medicine, and is known to have implications for patient safety, yet historically it has not been explicitly taught. Rather, it has been assumed that these skills will be learned by accumulating a body of knowledge and by observing expert clinicians. This course aims to assist students to develop their own clinical reasoning skills and promote their greater understanding of, and potential to benefit from, the clinical reasoning skills of others. The course takes place in the fourth or penultimate year, and is integrated with students' clinical placements, giving them opportunities to practise and quickly embed their learning. This course emphasises that clinical reasoning extends beyond initial diagnosis into all other aspects of clinical practice, particularly clinical management. It offers students a variety of challenging and interesting opportunities to engage with clinical reasoning across a wide range of clinical practice. It addresses bias through metacognition and increased self-awareness, considers some of the complexities of prescribing and non-pharmacological interventions, and promotes pragmatic evidence-based practice, information management within the consultation and the maximising of patient adherence. This article describes clinical reasoning-based classroom and community teaching. Early evaluation suggests that students value the course and benefit from it. © 2013 John Wiley & Sons Ltd.

A Return to "The Clinic" for Community Psychology: Lessons from a Clinical Ethnography in Urban American Indian Behavioral Health.

PubMed

Hartmann, William E; St Arnault, Denise M; Gone, Joseph P

2018-03-01

Community psychology (CP) abandoned the clinic and disengaged from movements for community mental health (CMH) to escape clinical convention and pursue growing aspirations as an independent field of context-oriented, community-engaged, and values-driven research and action. In doing so, however, CP positioned itself on the sidelines of influential contemporary movements that promote potentially harmful, reductionist biomedical narratives in mental health. We advocate for a return to the clinic-the seat of institutional power in mental health-using critical clinic-based inquiry to open sites for clinical-community dialogue that can instigate transformative change locally and nationally. To inform such works within the collaborative and emancipatory traditions of CP, we detail a recently completed clinical ethnography and offer "lessons learned" regarding challenges likely to re-emerge in similar efforts. Conducted with an urban American Indian community behavioral health clinic, this ethnography examined how culture and culture concepts (e.g., cultural competence) shaped clinical practice with socio-political implications for American Indian peoples and the pursuit of transformative change in CMH. Lessons learned identify exceptional clinicians versed in ecological thinking and contextualist discourses of human suffering as ideal partners for this work; encourage intense contextualization and constraining critique to areas of mutual interest; and support relational approaches to clinic collaborations. © Society for Community Research and Action 2017.

Psychotropics without borders: ethics and legal implications of internet-based access to psychiatric medications.

PubMed

Klein, Carolina A

2011-01-01

Medical practitioners are revisiting many of the ethics and the legal implications surrounding the clinical frameworks within which we operate. In today's world, distinguishing between virtual and physical reality continues to be increasingly difficult. The physician may be found grappling with the decision of whether to continue to treat a patient who may be obtaining psychotropic medications through the Internet. This article approaches some of the clinical and legal implications and the ethics regarding the availability of prescription psychotropics over the Internet.

Biological and Clinical Implications of Comorbidities in Parkinson’s Disease

PubMed Central

Santiago, Jose A.; Bottero, Virginie; Potashkin, Judith A.

2017-01-01

A wide spectrum of comorbidities has been associated with Parkinson’s disease (PD), a progressive neurodegenerative disease that affects more than seven million people worldwide. Emerging evidence indicates that chronic diseases including diabetes, depression, anemia and cancer may be implicated in the pathogenesis and progression of PD. Recent epidemiological studies suggest that some of these comorbidities may increase the risk of PD and precede the onset of motor symptoms. Further, drugs to treat diabetes and cancer have elicited neuroprotective effects in PD models. Nonetheless, the mechanisms underlying the occurrence of these comorbidities remain elusive. Herein, we discuss the biological and clinical implications of comorbidities in the pathogenesis, progression, and clinical management, with an emphasis on personalized medicine applications for PD. PMID:29255414

Modelling the resource implications of managing adults with Fabry disease in Italy.

PubMed

Guest, Julian F; Concolino, Daniela; Di Vito, Raffaele; Feliciani, Claudio; Parini, Rossella; Zampetti, Anna

2011-07-01

This study estimated the resource implications and budget impact of managing adults with Fabry disease in Italy, from the perspective of the Servizio Sanitario Nazionale (SSN). A decision model was constructed using published clinical outcomes and clinician-derived resource utilisation estimates depicting the management of adults with Fabry disease in Italy. The expected annual cost of managing 220 existing and 20 new Fabry patients in Italy was estimated to be €28·3 million. In an average year, patients receiving enzyme replacement therapy (ERT) with 0·2 mg kg(-1) agalsidase alfa (Replagal; Shire Human Genetic Therapies, Basingstoke, Hampshire, UK) or 1·0 mg kg(-1) agalsidase beta (Fabrazyme; Genzyme Europe BV, Naarden, The Netherlands) are collectively expected to make 4500 hospital attendances to a day ward for infusions, which equates to 2000 eight-h days on the day ward associated with ERT. If all ERT-treated patients received their infusions at home, there would be a marginal reduction in the annual health care cost to manage these patients, and the total annual number of days on the day ward associated with ERT in the second year could potentially be reduced from a mean 2000 to zero, thereby releasing substantial hospital resources for use by non-Fabry patients. Currently, only agalsidase alfa is licensed for home treatment in Italy; hence, only patients receiving this enzyme could be offered home treatment. Use of agalsidase alfa (0·2 mg kg(-1) ) instead of agalsidase beta (1·0 mg kg(-1)) has the potential to reduce health care costs and release hospital resources in different specialities for alternative use by non-Fabry patients, thereby improving the efficiency of the public health care system in Italy. © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.

Diatomic interhalogens - Systematics and implications of spectroscopic interatomic potentials and curve crossings

NASA Technical Reports Server (NTRS)

Child, M. S.; Bernstein, R. B.

1973-01-01

Spectroscopically derived potential curves for the low-lying excited states of homonuclear and heteronuclear diatomic interhalogens are systematized by the spin-orbit state of their dissociation products. The implications of spectroscopic interatomic potentials and curve crossings are discussed.

Iraq’s Debt Relief: Procedure and Potential Implications for International Debt Relief

DTIC Science & Technology

2008-10-02

Order Code RL33376 Iraq’s Debt Relief: Procedure and Potential Implications for International Debt Relief Updated October 2, 2008 Martin A. Weiss...4. TITLE AND SUBTITLE Iraq?s Debt Relief: Procedure and Potential Implications for International Debt Relief 5a. CONTRACT NUMBER 5b. GRANT NUMBER...b. ABSTRACT unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Iraq’s Debt Relief: Procedure

Policy Implications of the Use of Retail Clinics

PubMed Central

Weinick, Robin M.; Pollack, Craig Evan; Fisher, Michael P.; Gillen, Emily M.; Mehrotra, Ateev

2011-01-01

Abstract Retail clinics, located within larger retail stores, treat a limited number of acute conditions and offer a small set of preventive services. Although there are nearly 1,200 such clinics in the United States, a great deal about their utilization, relationships with other parts of the health care system, and quality of care remains unknown. The federal government has taken only limited action regarding retail clinics, and little evidence exists about the potential costs and benefits of integrating retail clinics into federal programs and initiatives. Through a literature review, semistructured interviews, and a panel of experts, the authors show that retail clinics have established a niche in the health care system based on their convenience and customer service. Levels of patient satisfaction and of the quality and appropriateness of care appear comparable to those of other provider types. However, we know little about the effects of retail clinic use on preventive services, care coordination, and care continuity. As clinics begin to expand into other areas of care, including chronic disease management, and as the number of patients with insurance increases and the shortage of primary care physicians continues, answering outstanding questions about retail clinics' role in the health care system will become even more important. These changes will create new opportunities for health policy to influence both how retail clinics function and the ways in which their care is integrated with that of other providers. PMID:28083196

Improving services for glaucoma care in Nigeria: implications for policy and programmes to achieve universal health coverage.

PubMed

Kyari, Fatima; Gilbert, Clare; Blanchet, Karl; Wormald, Richard

2017-05-01

Glaucoma in Africa is sometimes referred to as the silent thief of sight. In Nigeria, glaucoma is common, it is serious, ophthalmologists face many constraints in managing it, people do not even know they have it until it is advanced, patients do not understand or comply with treatment after they are diagnosed and the poor are more likely to be glaucoma blind. Available evidence indicates that the health system in Nigeria is failing to meet the needs of patients with glaucoma. Based on evidence, we propose future directions for improving services for glaucoma care in Nigeria, and the implications for policy and programmes to control glaucoma blindness, using a health system-oriented approach. Three complementary strategies are required: (i) strengthening clinical services for glaucoma-by developing models of glaucoma care, improving clinical treatment options, making medicines and equipment available, financing glaucoma care and training eye care workers; (ii) introducing initiatives for earlier detection of glaucoma in the clinic and approaches in the community and (iii) strengthening health system governance. Glaucoma is a complex disease to manage and addressing it as a public health problem is challenging. However, we need to change the paradigm to recognise that glaucoma is a potentially avoidable cause of blindness in Africa. 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/.

Epigenetics in Metastatic Breast Cancer: Its Regulation and Implications in Diagnosis, Prognosis and Therapeutics.

PubMed

Wu, Yuan Seng; Lee, Zhong Yang; Chuah, Lay-Hong; Mai, Chun Wai; Ngai, Siew Ching

2018-04-30

Despite advances in the treatment regimen, the high incidence rate of breast cancer (BC) deaths is mostly caused by metastasis. Recently, the aberrant epigenetic modifications, which involve DNA methylation, histone modifications and microRNA (miRNA) regulations become attractive targets to treat metastatic breast cancer (MBC). In this review, the epigenetic alterations of DNA methylation, histone modifications and miRNA regulations in regulating MBC is discussed. The preclinical and clinical trials of epigenetic drugs such as the inhibitor of DNA methyltransferase (DNMTi) and the inhibitor of histone deacetylase (HDACi), as a single or combined regimen with other epigenetic drug or standard chemotherapy drug to treat MBCs are discussed. The combined regimen of epigenetic drugs or with standard chemotherapy drugs enhance the therapeutic effect against MBC. Evidences that epigenetic changes could have implications in diagnosis, prognosis and therapeutics for MBC are also presented. Several genes have been identified as potential epigenetic biomarkers for diagnosis and prognosis, as well as therapeutic targets for MBC. Endeavors in clinical trials of epigenetic drugs against MBC should be continued although limited success has been achieved. Future discovery of epigenetic drugs from natural resources would be an attractive natural treatment regimen for MBC. Further research is warranted in translating research into clinical practice with the ultimate goal of treating MBC by epigenetic therapy in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mechanisms of change in control group drinking in clinical trials of brief alcohol intervention: implications for bias toward the null.

PubMed

Bernstein, Judith A; Bernstein, Edward; Heeren, Timothy C

2010-09-01

Reductions in control group consumption over time that are possibly related to research design affect the impact of brief alcohol interventions (BAI) in clinical settings. We conducted a systematic review to identify research design factors that may contribute to control group change, strategies to limit these effects and implications for researchers. Studies with control group n > 30 were selected if they published baseline and outcome consumption data, conducted trials in clinical settings in Anglophone countries and did not censor gender or age. Among 38 studies cited in 20 reviews through October 2009, 16 met criteria (n = 31-370). In 54%, controls received alcohol specific handouts, advice and/or referral. Both the number and depth of assessments were highly variable. The percentage change in consumption ranged from-0.10 to-0.84 (mean-0.32), and effect size from 0.04 to 0.70 (mean 0.37). Published data were insufficient for meta-analysis. Researchers should consider strategies to reduce the impact of research design factors, such as procedures to enhance sample diversity, blind subjects to study purpose to limit social desirability bias, reduce the number and depth of instruments (assessment reactivity), and finally, analytic techniques to decrease the impact of outliers and regression to the mean. This review identifies problems with retrospective analysis of predictors of control group change, and underscores the need to design prospective studies to permit identification, quantification and adjustment for potential sources of bias in BAI trials.

Managed care implications in managing rheumatoid arthritis.

PubMed

Owens, Gary M

2014-05-01

Rheumatoid arthritis (RA) is a systemic inflammatory form of arthritis characterized by joint inflammation, pain, swelling, and stiffness. While contemporary treatment strategies based on early diagnosis, aggressive treatment, and regular monitoring have helped a significant number of patients achieve evidence-based treatment goals, RA still presents substantial management challenges to both clinicians and patients, and has the potential to lead to severe disability over time. In addition to its significant clinical consequences, RA has important economic implications. Both direct and indirect medical costs associated with RA are significant, including costs of medications, ambulatory and office-based care, and quality-of-life and productivity costs. In addition, a significant proportion of patients with prevalent RA have associated cardiovascular disease and other comorbidities, further compounding healthcare costs and complicating management of this disorder. Clinically favorable and cost-effective management must focus on prevention of disease progression and the improved patient health status and productivity than can result from optimal disease control. With the myriad of treatment options both available and emerging, managed care organizations are faced with difficult decisions surrounding the most clinically and cost-effective allocation of treatments designed to improve disease outcomes for patients with RA. It is vital that managed care clinicians and providers analyze both the overall burden and the specific costs of RA. This will allow a better understanding of how costs and issues relating to healthcare utilization affect the treatment of patients with RA and impact individualized therapy, care coordination, and outcomes.

Alcohol-induced blackouts: A review of recent clinical research with practical implications and recommendations for future studies

PubMed Central

Wetherill, Reagan R.; Fromme, Kim

2016-01-01

Background Alcohol-induced blackouts, or memory loss for all or portions of events that occurred during a drinking episode, are reported by approximately 50% of drinkers and are associated with a wide range of negative consequences, including injury and death. As such, identifying the factors that contribute to and result from alcohol-induced blackouts is critical in developing effective prevention programs. Here, we provide an updated review (2010–2015) of clinical research focused on alcohol-induced blackouts, outline practical and clinical implications, and provide recommendations for future research. Methods A comprehensive, systematic literature review was conducted to examine all articles published between January 2010 through August 2015 that focused on examined vulnerabilities, consequences, and possible mechanisms for alcohol-induced blackouts. Results Twenty-sex studies reported on alcohol-induced blackouts. Fifteen studies examined prevalence and/or predictors of alcohol-induced blackouts. Six publications described consequences of alcohol-induced blackouts, and five studies explored potential cognitive and neurobiological mechanisms underlying alcohol-induced blackouts. Conclusions Recent research on alcohol-induced blackouts suggests that individual differences, not just alcohol consumption, increase the likelihood of experiencing an alcohol-induced blackout, and the consequences of alcohol-induced blackouts extend beyond the consequences related to the drinking episode to include psychiatric symptoms and neurobiological abnormalities. Prospective studies and a standardized assessment of alcohol-induced blackouts are needed to fully characterize factors associated with alcohol-induced blackouts and to improve prevention strategies. PMID:27060868

Alcohol-Induced Blackouts: A Review of Recent Clinical Research with Practical Implications and Recommendations for Future Studies.

PubMed

Wetherill, Reagan R; Fromme, Kim

2016-05-01

Alcohol-induced blackouts, or memory loss for all or portions of events that occurred during a drinking episode, are reported by approximately 50% of drinkers and are associated with a wide range of negative consequences, including injury and death. As such, identifying the factors that contribute to and result from alcohol-induced blackouts is critical in developing effective prevention programs. Here, we provide an updated review (2010 to 2015) of clinical research focused on alcohol-induced blackouts, outline practical and clinical implications, and provide recommendations for future research. A comprehensive, systematic literature review was conducted to examine all articles published between January 2010 through August 2015 that focused on vulnerabilities, consequences, and possible mechanisms for alcohol-induced blackouts. Twenty-six studies reported on alcohol-induced blackouts. Fifteen studies examined prevalence and/or predictors of alcohol-induced blackouts. Six publications described the consequences of alcohol-induced blackouts, and 5 studies explored potential cognitive and neurobiological mechanisms underlying alcohol-induced blackouts. Recent research on alcohol-induced blackouts suggests that individual differences, not just alcohol consumption, increase the likelihood of experiencing an alcohol-induced blackout, and the consequences of alcohol-induced blackouts extend beyond the consequences related to the drinking episode to include psychiatric symptoms and neurobiological abnormalities. Prospective studies and a standardized assessment of alcohol-induced blackouts are needed to fully characterize factors associated with alcohol-induced blackouts and to improve prevention strategies. Copyright © 2016 by the Research Society on Alcoholism.

Enteric short-chain fatty acids: microbial messengers of metabolism, mitochondria, and mind: implications in autism spectrum disorders

PubMed Central

MacFabe, Derrick F.

2015-01-01

Clinical observations suggest that gut and dietary factors transiently worsen and, in some cases, appear to improve behavioral symptoms in a subset of persons with autism spectrum disorders (ASDs), but the reason for this is unclear. Emerging evidence suggests ASDs are a family of systemic disorders of altered immunity, metabolism, and gene expression. Pre- or perinatal infection, hospitalization, or early antibiotic exposure, which may alter gut microbiota, have been suggested as potential risk factors for ASD. Can a common environmental agent link these disparate findings? This review outlines basic science and clinical evidence that enteric short-chain fatty acids (SCFAs), present in diet and also produced by opportunistic gut bacteria following fermentation of dietary carbohydrates, may be environmental triggers in ASD. Of note, propionic acid, a major SCFA produced by ASD-associated gastrointestinal bacteria (clostridia, bacteroides, desulfovibrio) and also a common food preservative, can produce reversible behavioral, electrographic, neuroinflammatory, metabolic, and epigenetic changes closely resembling those found in ASD when administered to rodents. Major effects of these SCFAs may be through the alteration of mitochondrial function via the citric acid cycle and carnitine metabolism, or the epigenetic modulation of ASD-associated genes, which may be useful clinical biomarkers. It discusses the hypothesis that ASDs are produced by pre- or post-natal alterations in intestinal microbiota in sensitive sub-populations, which may have major implications in ASD cause, diagnosis, prevention, and treatment. PMID:26031685