A Constructive Reframing of Student Roles and Systems Learning in Medical Education Using a Communities of Practice Lens.

PubMed

Gonzalo, Jed D; Thompson, Britta M; Haidet, Paul; Mann, Karen; Wolpaw, Daniel R

2017-12-01

Health systems are in the midst of a transformation that is being driven by a variety of forces. This has important implications for medical educators because clinical practice environments play a key role in learning and professional development, and evolving health systems are beginning to demand that providers have "systems-ready" knowledge, attitudes, and skills. Such implications provide a clear mandate for medical schools to modify their goals and prepare physicians to practice flexibly within teams and effectively contribute to the improvement of health care delivery. In this context, the concepts of value-added medical education, authentic student roles, and health systems science are emerging as increasingly important. In this Article, the authors use a lens informed by communities of practice theory to explore these three concepts, examining the implications that the communities of practice theory has in the constructive reframing of educational practices-particularly common student roles and experiences-and charting future directions for medical education that better align with the needs of the health care system. The authors apply several key features of the communities of practice theory to current experiential roles for students, then propose a new approach to students' clinical experiences-value-added clinical systems learning roles-that provides students with opportunities to make meaningful contributions to patient care while learning health systems science at the patient and population level. Finally, the authors discuss implications for professional role formation and anticipated challenges to the design and implementation of value-added clinical systems learning roles.

TCGA head Neck

Cancer.gov

Investigators with The Cancer Genome Atlas (TCGA) Research Network have discovered genomic differences – with potentially important clinical implications – in head and neck cancers caused by infection with the human papillomavirus (HPV).

An official American Thoracic Society/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease.

PubMed

Maltais, François; Decramer, Marc; Casaburi, Richard; Barreiro, Esther; Burelle, Yan; Debigaré, Richard; Dekhuijzen, P N Richard; Franssen, Frits; Gayan-Ramirez, Ghislaine; Gea, Joaquim; Gosker, Harry R; Gosselink, Rik; Hayot, Maurice; Hussain, Sabah N A; Janssens, Wim; Polkey, Micheal I; Roca, Josep; Saey, Didier; Schols, Annemie M W J; Spruit, Martijn A; Steiner, Michael; Taivassalo, Tanja; Troosters, Thierry; Vogiatzis, Ioannis; Wagner, Peter D

2014-05-01

Limb muscle dysfunction is prevalent in chronic obstructive pulmonary disease (COPD) and it has important clinical implications, such as reduced exercise tolerance, quality of life, and even survival. Since the previous American Thoracic Society/European Respiratory Society (ATS/ERS) statement on limb muscle dysfunction, important progress has been made on the characterization of this problem and on our understanding of its pathophysiology and clinical implications. The purpose of this document is to update the 1999 ATS/ERS statement on limb muscle dysfunction in COPD. An interdisciplinary committee of experts from the ATS and ERS Pulmonary Rehabilitation and Clinical Problems assemblies determined that the scope of this document should be limited to limb muscles. Committee members conducted focused reviews of the literature on several topics. A librarian also performed a literature search. An ATS methodologist provided advice to the committee, ensuring that the methodological approach was consistent with ATS standards. We identified important advances in our understanding of the extent and nature of the structural alterations in limb muscles in patients with COPD. Since the last update, landmark studies were published on the mechanisms of development of limb muscle dysfunction in COPD and on the treatment of this condition. We now have a better understanding of the clinical implications of limb muscle dysfunction. Although exercise training is the most potent intervention to address this condition, other therapies, such as neuromuscular electrical stimulation, are emerging. Assessment of limb muscle function can identify patients who are at increased risk of poor clinical outcomes, such as exercise intolerance and premature mortality. Limb muscle dysfunction is a key systemic consequence of COPD. However, there are still important gaps in our knowledge about the mechanisms of development of this problem. Strategies for early detection and specific treatments for this condition are also needed.

An Official American Thoracic Society/European Respiratory Society Statement: Update on Limb Muscle Dysfunction in Chronic Obstructive Pulmonary Disease

PubMed Central

Maltais, François; Decramer, Marc; Casaburi, Richard; Barreiro, Esther; Burelle, Yan; Debigaré, Richard; Dekhuijzen, P. N. Richard; Franssen, Frits; Gayan-Ramirez, Ghislaine; Gea, Joaquim; Gosker, Harry R.; Gosselink, Rik; Hayot, Maurice; Hussain, Sabah N. A.; Janssens, Wim; Polkey, Micheal I.; Roca, Josep; Saey, Didier; Schols, Annemie M. W. J.; Spruit, Martijn A.; Steiner, Michael; Taivassalo, Tanja; Troosters, Thierry; Vogiatzis, Ioannis; Wagner, Peter D.

2014-01-01

Background: Limb muscle dysfunction is prevalent in chronic obstructive pulmonary disease (COPD) and it has important clinical implications, such as reduced exercise tolerance, quality of life, and even survival. Since the previous American Thoracic Society/European Respiratory Society (ATS/ERS) statement on limb muscle dysfunction, important progress has been made on the characterization of this problem and on our understanding of its pathophysiology and clinical implications. Purpose: The purpose of this document is to update the 1999 ATS/ERS statement on limb muscle dysfunction in COPD. Methods: An interdisciplinary committee of experts from the ATS and ERS Pulmonary Rehabilitation and Clinical Problems assemblies determined that the scope of this document should be limited to limb muscles. Committee members conducted focused reviews of the literature on several topics. A librarian also performed a literature search. An ATS methodologist provided advice to the committee, ensuring that the methodological approach was consistent with ATS standards. Results: We identified important advances in our understanding of the extent and nature of the structural alterations in limb muscles in patients with COPD. Since the last update, landmark studies were published on the mechanisms of development of limb muscle dysfunction in COPD and on the treatment of this condition. We now have a better understanding of the clinical implications of limb muscle dysfunction. Although exercise training is the most potent intervention to address this condition, other therapies, such as neuromuscular electrical stimulation, are emerging. Assessment of limb muscle function can identify patients who are at increased risk of poor clinical outcomes, such as exercise intolerance and premature mortality. Conclusions: Limb muscle dysfunction is a key systemic consequence of COPD. However, there are still important gaps in our knowledge about the mechanisms of development of this problem. Strategies for early detection and specific treatments for this condition are also needed. PMID:24787074

Germline genetic variants with implications for disease risk and therapeutic outcomes.

PubMed

Pasternak, Amy L; Ward, Kristen M; Luzum, Jasmine A; Ellingrod, Vicki L; Hertz, Daniel L

2017-10-01

Genetic testing has multiple clinical applications including disease risk assessment, diagnosis, and pharmacogenomics. Pharmacogenomics can be utilized to predict whether a pharmacologic therapy will be effective or to identify patients at risk for treatment-related toxicity. Although genetic tests are typically ordered for a distinct clinical purpose, the genetic variants that are found may have additional implications for either disease or pharmacology. This review will address multiple examples of germline genetic variants that are informative for both disease and pharmacogenomics. The discussed relationships are diverse. Some of the agents are targeted for the disease-causing genetic variant, while others, although not targeted therapies, have implications for the disease they are used to treat. It is also possible that the disease implications of a genetic variant are unrelated to the pharmacogenomic implications. Some of these examples are considered clinically actionable pharmacogenes, with evidence-based, pharmacologic treatment recommendations, while others are still investigative as areas for additional research. It is important that clinicians are aware of both the disease and pharmacogenomic associations of these germline genetic variants to ensure patients are receiving comprehensive personalized care. Copyright © 2017 the American Physiological Society.

Is a clinical sociolinguistics possible?

PubMed

Ball, M J

1992-01-01

This paper considers the idea of developing a clinical sociolinguistics. Various areas of the field are examined, and the importance of the 'core' area of the correlation of non-linguistic variables with linguistic variables stressed. Issues concerning language and class, region, sex, age and context of utterance are investigated, together with the implications for clinical linguistics. Finally, the difficulty of integrating such issues into clinical assessment is explored, and a tentative step forward suggested along the lines of a 'clinical sociolinguistic checklist'.

Nutritional Needs of the Child with a Handicap or Chronic Illness. Manual II: Clinical Nutrition. Presentations from a National Interdisciplinary Symposium.

ERIC Educational Resources Information Center

Ekvall, Shirley M.; Wheby, Elizabeth A.

The following papers were presented at a symposium on clinical nutrition for the child who is chronically ill or handicapped: (1) "Food Allergy"; (2) "Anemia and the Chronically Ill or Handicapped Child"; (3) "Nutrition and Neurotransmitters--Clinical Implications"; (4) "The Importance of Lipid Type in the Diet after Burn Injury"; (5) "Advances of…

Developing an evidence-based practice protocol: implications for midwifery practice.

PubMed

Carr, K C

2000-01-01

Evidence-based practice is defined and its importance to midwifery practice is presented. Guidelines are provided for the development of an evidence-based practice protocol. These include: identifying the clinical question, obtaining the evidence, evaluating the validity and importance of the evidence, synthesizing the evidence and applying it to the development of a protocol or clinical algorithm, and, finally, developing an evaluation plan or measurement strategy to see if the new protocol is effective.

Co-Occurring ODD and GAD Symptom Groups: Source-Specific Syndromes and Cross-Informant Comorbidity

ERIC Educational Resources Information Center

Drabick, Deborah A. G.; Gadow, Kenneth D.; Loney, Jan

2008-01-01

Despite important clinical and nosological implications, the comorbidity of oppositional defiant disorder (ODD) and generalized anxiety disorder (GAD) has received little attention. A clinic-based sample of 243 boys (ages 6-10 years), their parents, and teachers participated in an evaluation that involved assessments of behavioral, academic, and…

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.

Name Changes in Medically Important Fungi and Their Implications for Clinical Practice

PubMed Central

de Hoog, G. Sybren; Chaturvedi, Vishnu; Denning, David W.; Dyer, Paul S.; Frisvad, Jens Christian; Geiser, David; Gräser, Yvonne; Guarro, Josep; Haase, Gerhard; Kwon-Chung, Kyung-Joo; Meyer, Wieland; Pitt, John I.; Samson, Robert A.; Tintelnot, Kathrin; Vitale, Roxana G.; Walsh, Thomas J.

2014-01-01

Recent changes in the Fungal Code of Nomenclature and developments in molecular phylogeny are about to lead to dramatic changes in the naming of medically important molds and yeasts. In this article, we present a widely supported and simple proposal to prevent unnecessary nomenclatural instability. PMID:25297326

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.

Anatomy of the pterygomandibular space - clinical implication and review.

PubMed

Lipski, Marcin; Lipska, Weronika; Motyl, Sylwia; Gladysz, Tomasz; Iskra, Tomasz

2013-01-01

The aim of this study was to present review of the pterygomandibular space with some referrals to clinical practice, specially to the methods of lower teeth anesthesia. Pterygomandibular space is a clinically important region which is commonly missing in anatomical textbooks. More attention should be paid to it both from theoretical and practical point of view, especially in teaching the students of first year of dental studies.

Evaluation and applications of the clinically significant change method with the Violence Risk Scale-Sexual Offender version: implications for risk-change communication.

PubMed

Olver, Mark E; Beggs Christofferson, Sarah M; Wong, Stephen C P

2015-02-01

We examined the use of the clinically significant change (CSC) method with the Violence Risk Scale-Sexual Offender version (VRS-SO), and its implications for risk communication, in a combined sample of 945 treated sexual offenders from three international settings, followed up for a minimum 5 years post-release. The reliable change (RC) index was used to identify thresholds of clinically meaningful change and to create four CSC groups (already okay, recovered, improved, unchanged) based on VRS-SO dynamic scores and amount of change made. Outcome analyses demonstrated important CSC-group differences in 5-year rates of sexual and violent recidivism. However, when baseline risk was controlled via Cox regression survival analysis, the pattern and magnitude of CSC-group differences in sexual and violent recidivism changed to suggest that observed variation in recidivism base rates could be at least partly explained by pre-existing group differences in risk level. Implications for communication of risk-change information and applications to clinical practice are discussed. Copyright © 2015 John Wiley & Sons, Ltd.

Predictive and Prognostic Models: Implications for Healthcare Decision-Making in a Modern Recession

PubMed Central

Vogenberg, F. Randy

2009-01-01

Various modeling tools have been developed to address the lack of standardized processes that incorporate the perspectives of all healthcare stakeholders. Such models can assist in the decision-making process aimed at achieving specific clinical outcomes, as well as guide the allocation of healthcare resources and reduce costs. The current efforts in Congress to change the way healthcare is financed, reimbursed, and delivered have rendered the incorporation of modeling tools into the clinical decision-making all the more important. Prognostic and predictive models are particularly relevant to healthcare, particularly in the clinical decision-making, with implications for payers, patients, and providers. The use of these models is likely to increase, as providers and patients seek to improve their clinical decision process to achieve better outcomes, while reducing overall healthcare costs. PMID:25126292

Confronting the Inevitable: A Conceptual Model of Miscarriage for Use in Clinical Practice and Research

ERIC Educational Resources Information Center

Wojnar, Danuta M.; Swanson, Kristen M.; Adolfsson, Ann-Sofie

2011-01-01

In spite of scientific evidence that miscarriage has negative psychological consequences for many individuals and couples, silence and dismissal continue to surround this invisible loss in North American culture and beyond. The grief and sorrow of miscarriage has important implications for clinical practice. It indicates a need for therapeutic…

Midodrine Exacerbates Promethazine-induced Akathisia

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Shi, Shang-Jin; Meck, Janice V.

2006-01-01

The study of physiological changes during spaceflight, and the pursuit of remedies to counteract those changes, often requires unique research protocols that lead to unexpected findings; some with important clinical implications. In our research into the development of treatments to counteract the detrimental cardiovascular effects of spaceflight, we have discovered an important drug interaction between promethazine and midodrine.

Treatment Fidelity: Its Importance and Reported Frequency in Aphasia Treatment Studies

ERIC Educational Resources Information Center

Hinckley, Jacqueline J.; Douglas, Natalie F.

2013-01-01

Purpose: Treatment fidelity is a measure of the reliability of the administration of an intervention in a treatment study. It is an important aspect of the validity of a research study, and it has implications for the ultimate implementation of evidence-supported interventions in typical clinical settings. Method: Aphasia treatment studies…

Practices and Policies of Clinical Exome Sequencing Providers: Analysis and Implications

PubMed Central

Jamal, Seema M.; Yu, Joon-Ho; Chong, Jessica X.; Dent, Karin M.; Conta, Jessie H.; Tabor, Holly K.; Bamshad, Michael J.

2013-01-01

Exome and whole genome sequencing (ES/WGS) offer potential advantages over traditional approaches to diagnostic genetic testing. Consequently, use of ES/WGS in clinical settings is rapidly becoming commonplace. Yet there are myriad moral, ethical, and perhaps legal implications attached to the use of ES and health care professionals and institutions will need to consider these implications in the context of the varied practices and policies of ES service providers. We developed “core elements” of content and procedures for informed consent, data sharing, and results management and a quantitative scale to assess the extent to which research protocols met the standards established by these core elements. We then used these tools to evaluate the practices and policies of each of the 6 U.S. CLIA-certified labs offering clinical ES. Approaches toward informed consent, data sharing, and results return vary widely among ES providers as do the overall potential merits and disadvantages of each, and more importantly, the balance between the two. PMID:23610049

Community health clinical education in Canada: part 2--developing competencies to address social justice, equity, and the social determinants of health.

PubMed

Cohen, Benita E; Gregory, David

2009-01-01

Recently, several Canadian professional nursing associations have highlighted the expectations that community health nurses (CHNs) should address the social determinants of health and promote social justice and equity. These developments have important implications for (pre-licensure) CHN clinical education. This article reports the findings of a qualitative descriptive study that explored how baccalaureate nursing programs in Canada address the development of competencies related to social justice, equity, and the social determinants of health in their community health clinical courses. Focus group interviews were held with community health clinical course leaders in selected Canadian baccalaureate nursing programs. The findings foster understanding of key enablers and challenges when providing students with clinical opportunities to develop the CHN role related to social injustice, inequity, and the social determinants of health. The findings may also have implications for nursing programs internationally that are addressing these concepts in their community health clinical courses.

Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 1, Pathological Background and Clinical Implications

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

Sun, Fei, E-mail: feisun@ccmijesususon.com; Crisóstomo, Verónica, E-mail: crisosto@ccmijesususon.com; Báez-Díaz, Claudia, E-mail: cbaez@ccmijesususon.com

Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance.more » BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.« less

Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 1, Pathological Background and Clinical Implications.

PubMed

Sun, Fei; Crisóstomo, Verónica; Báez-Díaz, Claudia; Sánchez, Francisco M

2016-01-01

Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance. BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.

Androgens: basic biology and clinical implication.

PubMed

Orwoll, E S

2001-10-01

Although androgens have been considered essential modulators of bone biology in men, recent studies have indicated that estrogen may have an important, if not dominant, role. Nevertheless, there is strong evidence that androgens have independent skeletal actions. Nonaromatizable androgens influence a variety of aspects of bone cell biology and are capable of modulating bone remodeling and bone mass. It appears that androgens are particularly important in the control of periosteal bone formation, an effect that might underlie the gender difference in bone size. Alterations in androgen receptor function affect bone metabolism, and new information suggests that androgens modulate receptor homeostasis. The clinical implications of androgen effects, and how they interact with those of estrogens, are somewhat unclear. It is likely that overall bone homeostasis and gender differences depend on a combination of androgenic and estrogenic actions. Androgens may well provide advantages in the prevention and therapy of metabolic bone disorders in both men and women.

Religion, health and medicine in African Americans: implications for physicians.

PubMed

Levin, Jeff; Chatters, Linda M; Taylor, Robert Joseph

2005-02-01

Recent years have seen a burgeoning of research and writing on the connections between religion and health. The very best of this work comes from epidemiologic studies of African Americans. This paper summarizes results of these investigations, including findings identifying effects of religious participation on both physical and mental health outcomes. Evidence mostly supports a protective religious effect on morbidity and mortality and on depressive symptoms and overall psychological distress among African Americans. This paper also carefully discusses what the results of these studies mean and do not mean, an important consideration due to frequent misinterpretations of findings on this topic. Because important distinctions between epidemiologic and clinical studies tend to get glossed over, reports of religion-health associations oftentimes draw erroneous conclusions that foster unrealistic expectations about the role of faith and spirituality in health and healing. Finally, implications are discussed for clinical practice, medical education and public health.

Religion, health and medicine in African Americans: implications for physicians.

PubMed Central

Levin, Jeff; Chatters, Linda M.; Taylor, Robert Joseph

2005-01-01

Recent years have seen a burgeoning of research and writing on the connections between religion and health. The very best of this work comes from epidemiologic studies of African Americans. This paper summarizes results of these investigations, including findings identifying effects of religious participation on both physical and mental health outcomes. Evidence mostly supports a protective religious effect on morbidity and mortality and on depressive symptoms and overall psychological distress among African Americans. This paper also carefully discusses what the results of these studies mean and do not mean, an important consideration due to frequent misinterpretations of findings on this topic. Because important distinctions between epidemiologic and clinical studies tend to get glossed over, reports of religion-health associations oftentimes draw erroneous conclusions that foster unrealistic expectations about the role of faith and spirituality in health and healing. Finally, implications are discussed for clinical practice, medical education and public health. PMID:15712787

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.

Controversies in the physiological basis of the 'anaerobic threshold' and their implications for clinical cardiopulmonary exercise testing.

PubMed

Hopker, J G; Jobson, S A; Pandit, J J

2011-02-01

This article reviews the notion of the 'anaerobic threshold' in the context of cardiopulmonary exercise testing. Primarily, this is a review of the proposed mechanisms underlying the ventilatory and lactate response to incremental exercise, which is important to the clinical interpretation of an exercise test. Since such tests are often conducted for risk stratification before major surgery, a failure to locate or justify the existence of an anaerobic threshold will have some implications for clinical practice. We also consider alternative endpoints within the exercise response that might be better used to indicate a patient's capacity to cope with the metabolic demands encountered both during and following major surgery. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

Molecular biology of pancreatic cancer: how useful is it in clinical practice?

PubMed

Sakorafas, George H; Smyrniotis, Vasileios

2012-07-10

During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice. To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. Reports about clinical implications of molecular biology in patients with pancreatic cancer were retrieved from PubMed. These reports were selected on the basis of their clinical relevance, and the data of their publication (preferentially within the last 5 years). Emphasis was placed on reports investigating diagnostic, prognostic, and therapeutic implications. Molecular biology can be used to identify individuals at high-risk for pancreatic cancer development. Intensive surveillance is indicated in these patients to detect pancreatic neoplasia ideally at a preinvasive stage, when curative resection is still possible. Molecular biology can also be used in the diagnosis of pancreatic cancer, with molecular analysis on samples of biologic material, such as serum or plasma, duodenal fluid or preferentially pure pancreatic juice, pancreatic cells or tissue, and stools. Molecular indices have also prognostic significance. Finally, molecular biology may have therapeutic implications by using various therapeutic approaches, such as antiangiogenic factors, purine synthesis inhibitors, matrix metalloproteinase inhibitors, factors modulating tumor-stroma interaction, inactivation of the hedgehog pathway, gene therapy, oncolytic viral therapy, immunotherapy (both passive as well as active) etc. Molecular biology may have important clinical implications in patients with pancreatic cancer and represents one of the most active areas on cancer research. Hopefully clinical applications of molecular biology in pancreatic cancer will expand in the future, improving the effectiveness of treatment and prognosis of patients with pancreatic cancer. 

Changes in drug transport and metabolism and their clinical implications in non-alcoholic fatty liver disease.

PubMed

Dietrich, Christoph G; Rau, Monika; Jahn, Daniel; Geier, Andreas

2017-06-01

The incidence of non-alcoholic fatty liver disease (NAFLD) is rising, especially in Western countries. Drug treatment in patients with NAFLD is common since it is linked to other conditions like diabetes, obesity, and cardiovascular disease. Consequently, changes in drug metabolism may have serious clinical implications. Areas covered: A literature search for studies in animal models or patients with obesity, fatty liver, non-alcoholic steatohepatitis (NASH) or NASH cirrhosis published before November 2016 was performed. After discussing epidemiology and animal models for NAFLD, we summarized both basic as well as clinical studies investigating changes in drug transport and metabolism in NAFLD. Important drug groups were assessed separately with emphasis on clinical implications for drug treatment in patients with NAFLD. Expert opinion: Given the frequency of NAFLD even today, a high degree of drug treatment in NAFLD patients appears safe and well-tolerated despite considerable changes in hepatic uptake, distribution, metabolism and transport of drugs in these patients. NASH causes changes in biliary excretion, systemic concentrations, and renal handling of drugs leading to alterations in drug efficacy or toxicity under specific circumstances. Future clinical drug studies should focus on this special patient population in order to avoid serious adverse events in NAFLD patients.

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.

Osteoarthritis subpopulations and implications for clinical trial design

PubMed Central

2011-01-01

Treatment guidelines for osteoarthritis have stressed the need for research on clinical predictors of response to different treatments. However, identifying such clinical predictors of response is less easy than it seems, and there is not a given classification of osteoarthritis subpopulations. This review article highlights the key methodical issues when analyzing and designing clinical studies to detect important subgroups with respect to treatment effect. In addition, we discuss the main osteoarthritis subpopulations and give examples of how specific treatment effects in these subpopulations have been assessed. PMID:21470393

HUMAN CLINICAL STUDIES OF CONCENTRATED AMBIENT ULTRAFINE AND FINE PARTICLES

EPA Science Inventory

Confirmation of our hypothesis that exposure to ambient ultrafine and fine particles promotes coagulation and alters cardiac function will have important implications for air pollution regulatory efforts, and will provide new approaches for the prevention of cardiovascular hea...

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.

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

Atypical femur fractures: a review of the evidence and its implication to clinical practice

PubMed Central

Girgis, Christian M.

2011-01-01

Whilst bisphosphonates are an established modality in the treatment of osteoporosis, there have been increasing concerns regarding the risk of an unusual form of femur fracture amongst patients receiving bisphosphonates for prolonged periods. These fractures, referred to as ‘atypical’, have been characterized by a number of clinical and radiographic features that distinguish them from ‘typical’ osteoporotic fractures. The evidence base is currently split between a large number of case series demonstrating an association between the occurrence of atypical fractures and bisphosphonate use and several population-based studies that do not confirm such an association. Hence, a degree of uncertainty surrounds this important issue. In this review, we examine the emerging evidence on atypical femur fractures, assess hypotheses on their biomechanical evolution and discuss the wider clinical implications of this phenomenon. PMID:22870488

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.

CDC staging based on absolute CD4 count and CD4 percentage in an HIV-1-infected Indian population: treatment implications

PubMed Central

Vajpayee, M; Kaushik, S; Sreenivas, V; Wig, N; Seth, P

2005-01-01

CD4+ T-cell levels are an important criterion for categorizing HIV-related clinical conditions according to the CDC classification system and are therefore important in the management of HIV by initiating antiretroviral therapy and prophylaxis for opportunistic infections due to HIV among HIV-infected individuals. However, it has been observed that the CD4 counts are affected by the geographical location, race, ethnic origin, age, gender and changes in total and differential leucocyte counts. In the light of this knowledge, we classified 600 HIV seropositive antiretroviral treatment (ART)-naïve Indian individuals belonging to different CDC groups A, B and C on the basis of CDC criteria of both CD4% and CD4 counts and receiver operating characteristic (ROC) curves were generated. Importantly, CDC staging on the basis of CD4% indicated significant clinical implications, requiring an early implementation of effective antiretroviral treatment regimen in HIV-infected individuals deprived of treatment when classified on the basis of CD4 counts. PMID:16045738

Critical Review of Data Evaluation in Teaching Clinics of Traditional Chinese Medicine Outside China: Implications for Education.

PubMed

Jiang, Jian; Peng, Wenbo; Gu, Tieguang; King, Catherine; Yin, J Kevin

2016-01-01

The increasing acceptance of traditional Chinese medicine (TCM) worldwide has highlighted the importance of ensuring the provision of high-quality TCM clinical education. This clinical training should be partly guided by a robust assessment of patient data outcomes in TCM teaching clinics. We undertook a comprehensive literature review to examine the data evaluation in TCM teaching clinics outside China and its implications for TCM education. Literature was retrieved via MEDLINE (from 1946 to January 2015), EMBASE (from 1980 to February 2015), and Google Scholar for studies conducted outside China. The search was restricted to English articles reporting empirical findings related to the assessments of patient data in TCM teaching clinics, with implications for TCM education in countries other than China. Only seven articles from six studies met the inclusion criteria. The characteristics and main symptoms of patients who received any TCM treatment in the context of teaching clinics among all included studies were similar. Symptom relief as well as a high level of patient satisfaction with TCM treatment were found in TCM teaching clinics. Conventional healthcare providers and other complementary practitioners were not the main source of referral to TCM practitioners but rather patients׳ friends/relatives. Patients received acupuncture treatment more frequently than treatments utilizing Chinese herbal medicine in teaching clinics. A standardized and consistent framework for patient records within TCM teaching clinics is currently lacking. There was no robust study which "translated" TCM clinic data evaluation findings into implications for TCM education and clinical training. Recognizing that TCM evolves over time and its practice varies in different settings, there is an urgent need to conduct large-scale, rigorous evaluations of TCM clinic data to address the findings of our review, with the purpose of better informing TCM education and clinical training in countries beyond China. Expansions for scientific efforts supporting TCM education are essential to ensure that qualified TCM practitioners are able to provide safe, efficacious, and cost-effective TCM treatment modalities. Copyright © 2016 Elsevier Inc. All rights reserved.

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

On heterogeneity of treatment effects and clinical freedom.

PubMed

Sacristán, J A; Avendaño-Solá, C

2015-01-01

Three decades ago, John R Hampton announced the death of clinical freedom. Since then, evidence-based medicine has been the predominant paradigm in clinical research. By applying a population-based approach, the randomised controlled trial has become the cornerstone for demonstrating the overall effect of a treatment and for developing guidelines. The new patient-centred medicine movement is rediscovering the important implications of heterogeneity of treatment effects for clinical practice and that a better understanding of such variability can contribute to improve health outcomes for individual patients through practicing a science-based clinical freedom. © 2015 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.

Thyroid Hormone Disruption Effects Lamination of the Neocortex but not the Cerebellum in a Model of Developmental Hypothyroidism and Hypothyroxinemia

EPA Science Inventory

Introduction: Research on neurodevelopmental changes resulting from thyroid hormone (TH) disruption has important basic and clinical implications. We previously demonstrated, in a rodent model, that developmental hypothyroidism or hypothyroxinemia can cause ...

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

Glucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity

PubMed Central

Anandhakrishnan, Ananthi; Korbonits, Márta

2016-01-01

Though the pathophysiology of clinical obesity is undoubtedly multifaceted, several lines of clinical evidence implicate an important functional role for glucagon-like peptide 1 (GLP-1) signalling. Clinical studies assessing GLP-1 responses in normal weight and obese subjects suggest that weight gain may induce functional deficits in GLP-1 signalling that facilitates maintenance of the obesity phenotype. In addition, genetic studies implicate a possible role for altered GLP-1 signalling as a risk factor towards the development of obesity. As reductions in functional GLP-1 signalling seem to play a role in clinical obesity, the pharmacological replenishment seems a promising target for the medical management of obesity in clinical practice. GLP-1 analogue liraglutide at a high dose (3 mg/d) has shown promising results in achieving and maintaining greater weight loss in obese individuals compared to placebo control, and currently licensed anti-obesity medications. Generally well tolerated, provided that longer-term data in clinical practice supports the currently available evidence of superior short- and long-term weight loss efficacy, GLP-1 analogues provide promise towards achieving the successful, sustainable medical management of obesity that remains as yet, an unmet clinical need. PMID:28031776

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".

Malignant disease and dentistry.

PubMed

Walton, Graham; Seymour, Robin A

2009-11-01

Reports of an ageing population, increasing incidence of malignancy and improved treatments mean that dentists may have an increasing number of patients with, or who have recovered from, a malignancy. Dental professionals are expected to have an understanding of this important disease group so that appropriate dental care can be provided safely. In this first of three articles, we shall describe the important epidemiological and clinical features of the commonest malignancies in the United Kingdom. Dentists should understand the clinical implications of a patient with, or recovering from, a malignancy. This article gives a summary of the relevant features of the commonest malignancies.

Facial emotion recognition deficits: The new face of schizophrenia

PubMed Central

Behere, Rishikesh V.

2015-01-01

Schizophrenia has been classically described to have positive, negative, and cognitive symptom dimension. Emerging evidence strongly supports a fourth dimension of social cognitive symptoms with facial emotion recognition deficits (FERD) representing a new face in our understanding of this complex disorder. FERD have been described to be one among the important deficits in schizophrenia and could be trait markers for the disorder. FERD are associated with socio-occupational dysfunction and hence are of important clinical relevance. This review discusses FERD in schizophrenia, challenges in its assessment in our cultural context, its implications in understanding neurobiological mechanisms and clinical applications. PMID:26600574

Childhood Externalizing Behavior: Theory and Implications

PubMed Central

Liu, Jianghong

2006-01-01

TOPIC Childhood externalizing behavior PURPOSE To analyze the construct of externalizing behavior (aggression, delinquency, and hyperactivity), illustrate the biosocial model of childhood externalizing, and draw clinical implications for nursing research and practice. SOURCES A review of the literature based on psychological, psychiatric, and nursing journals. CONCLUSIONS A better understanding of childhood externalizing behavior problems and the risk factors underlying them are essential to prevent them. The employment of an integrative biosocial perspective is argued to be important in understanding this behavior. PMID:15535385

Juxtapapillary duodenal diverticula early and late clinical and therapeutical implications.

PubMed

Straja, D; Marincaş, M; Alecu, M; Boroghina, G; Simion, L; Stanescu, A; Drilea, E; Brătucu, E

2009-01-01

The aim of this paper is to identify the early and late implications of JPDD for biliary pathology, as well as for endoscopic therapy and classical surgery dealing mainly with lithiasis. This paper is based on a retrospective study comprising a number of 675 ERCP performed on 601 patients between 1997-2007, out of which 399 cases were followed by therapeutic measures. A total of 79 procedures were performed on 65 cases with JPDD. The main criteria were: gender, age, indications regarding the performance of ERCP+/-ES, complications that occurred while carrying out these procedures. In all the cases examined (601) the percentage of JPDD reported was of 10.81%. The rate of complications in the sphincterotomized patients without JPDD was 5.75% and the rate in the sphincterotomized patients with JPDD was 14.89%. In conclusion, the paper discusses the clinical and therapeutic implications of JPDD in biliary pathology. It has been found that JPDD is an important etiological cause for the late diseases occurring after cholelithiasis surgery. JPDD also leads to immediate therapeutic implications such as: difficult cannulation and high incidence of ERCP+/-ES complications.

The Francis Report--Implications for the Education and Training of Dental Professionals.

PubMed

Bissell, Vince; Felix, David H

2015-04-01

This paper explores the implications of the Francis Report for education of the dental team. It considers selection of candidates for training, issues relating to the curriculum itself, including assessment and the importance of listening to trainees. The overriding importance of the 'informal' or 'hidden' curriculum, through which students and trainees observe their teachers and develop a sense of the professional and ethical culture within an educational institution, is stressed. Clinical relevance: Sound education, rooted in the recognized ethical principles highlighted in the Francis Report, is essential to the delivery of a dental work force that will deliver care according to the fundamental standards laid down by the GDC.

Adiposity, cardiometabolic risk, and vitamin D status: the Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

Objective: Because vitamin D deficiency is associated with a variety of chronic diseases, understanding the characteristics that promote vitamin D deficiency in otherwise healthy adults could have important clinical implications. Few studies relating vitamin D deficiency to obesity have included d...

The importance of least restrictive care: the clinical implications of a recent High Court decision on negligence.

PubMed

Ryan, Christopher James; Callaghan, Sascha; Large, Matthew

2015-08-01

This paper aims to explain the meaning and implications for practice of the High Court of Australia's finding in the negligence case, Hunter and New England Local Health District v McKenna [2014] HCA 44. The facts of the case and the law of negligence are reviewed before reporting the Court's decision. The High Court found that the obligation upon doctors to provide the least restrictive option for care that was imposed by the, then applicable, Mental Health Act 1990 (NSW) was inconsistent with an obligation that might otherwise be imposed by a common law duty to have regard to the interests of those with whom a psychiatric patient may come into contact if not detained. The Court's finding underlines the importance of clinicians documenting their clinical reasoning around why their negotiated management plan was the option least restrictive of the patient's freedom and most protective of his or her human rights. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Clinical review: Ethnic differences in bone mass--clinical implications.

PubMed

Leslie, William D

2012-12-01

Differences in bone mineral density (BMD) as assessed with dual-energy x-ray absorptiometry are observed between geographic and ethnic groups, with important implications in clinical practice. PubMed was employed to identify relevant studies. A review of the literature was conducted, and data were summarized and integrated. The available data highlight the complex ethnic variations in BMD, which only partially account for observed variations in fracture rates. Factors contributing to ethnic differences include genetics, skeletal size, body size and composition, lifestyle, and social determinants. Despite BMD differences, the gradient of risk for fracture from BMD and other clinical risk factors appears to be similar across ethnic groups. Furthermore, BMD variation is greater within an ethnic population than between ethnic populations. New imaging technologies have identified ethnic differences in bone geometry, volumetric density, microarchitecture, and estimated bone strength that may contribute to a better understanding of ethnic differences in fracture risk. Factors associated with ethnicity affect BMD and fracture risk through direct and indirect mechanisms.

Clinical leadership in contemporary clinical practice: implications for nursing in Australia.

PubMed

Davidson, P M; Elliott, D; Daly, J

2006-04-01

Leadership in the clinical practice environment is important to ensure both optimal patient outcomes and successive generations of motivated and enthusiastic clinicians. The present paper seeks to define and describe clinical leadership and identify the facilitators and barriers to clinical leadership. We also describe strategies to develop clinical leaders in Australia. Key drivers to the development of nursing leaders are strategies that recognize and value clinical expertise. These include models of care that highlight the importance of the nursing role; evidence-based practice and measurement of clinical outcomes; strategies to empower clinicians and mechanisms to ensure participation in clinical decision-making. Significant barriers to clinical leadership are organizational structures that preclude nurses from clinical decision making; the national shortage of nurses; fiscal constraints; absence of well evaluated models of care and trends towards less skilled clinicians. Systematic, strategic initiatives are required to nurture and develop clinical leaders. These strategies need to be collegial collaborations between the academic and health care sectors in order to provide a united voice for advancing the nursing profession.

Inflammatory Bowel Disease: Influence and Implications in Reproduction

PubMed Central

Glover, Louise E.; Fennimore, Blair; Wingfield, Mary

2016-01-01

The incidence and prevalence of inflammatory bowel disease (IBD) continues to rise with time, signifying its emergence as a global disease. Clinical onset of IBD, comprising Crohn’s disease and ulcerative colitis, typically occurs prior to or at peak reproductive age. Although active disease in female patients is associated with reduced fertility and adverse obstetric outcomes in pregnancy, the molecular mechanisms underlying this altered reproductive course, as well as its impact on IBD transmission to offspring, remain poorly understood. Clinical and experimental studies have now begun to elucidate the hormonal, environmental and microbial factors that modulate immune-reproductive crosstalk in IBD, and define their impact on maternal health, fetal development and heritability of disease risk. Evolving insight into maternal-fetal imprinting in IBD has important implications for patient counseling and disease management during pregnancy, and may help predict clinical outcomes for both mother and child. PMID:27537054

The genomic landscape of chronic lymphocytic leukaemia: biological and clinical implications.

PubMed

Strefford, Jonathan C

2015-04-01

Chronic lymphocytic leukaemia (CLL) remains at the forefront of the genetic analysis of human tumours, principally due its prevalence, protracted natural history and accessibility to suitable material for analysis. With the application of high-throughput genetic technologies, we have an unbridled view of the architecture of the CLL genome, including a comprehensive description of the copy number and mutational landscape of the disease, a detailed picture of clonal evolution during pathogenesis, and the molecular mechanisms that drive genomic instability and therapeutic resistance. This work has nuanced the prognostic importance of established copy number alterations, and identified novel prognostically relevant gene mutations that function within biological pathways that are attractive treatment targets. Herein, an overview of recent genomic discoveries will be reviewed, with associated biological and clinical implications, and a view into how clinical implementation may be facilitated. © 2014 John Wiley & Sons Ltd.

Key issues in the management of patients with systemic lupus erythematosus: latest developments and clinical implications

PubMed Central

Jordan, Natasha; D’Cruz, David

2015-01-01

Systemic lupus erythematous (SLE) is a chronic multisystem disease with significant associated morbidity and mortality. A deeper understanding of the pathogenesis of SLE has led to the development of biologic agents, primarily targeting B cells and others inhibiting costimulatory molecules, type I interferons and cytokines such as interleukin-6. Several of these agents have been studied in clinical trials; some have shown promise while others have yielded disappointing results. Economic and regulatory issues continue to hamper the availability of such therapies for SLE patients. With increasing recognition that recurrent flares of disease activity lead to long-term damage accrual, one of the most important recent developments in patient management has been the concept of treat-to-target in SLE while minimizing patient exposure to excessive corticosteroid and other immunosuppressive therapy. This article reviews these key issues in SLE management, outlining recent developments and clinical implications for patients. PMID:26622325

Mechanisms of peripheral immune-cell-mediated analgesia in inflammation: clinical and therapeutic implications.

PubMed

Hua, Susan; Cabot, Peter J

2010-09-01

Peripheral mechanisms of endogenous pain control are significant. In peripheral inflamed tissue, an interaction between immune-cell-derived opioids and opioid receptors localized on sensory nerve terminals results in potent, clinically measurable analgesia. Opioid peptides and the mRNA encoding their precursor proteins are present in immune cells. These cells 'home' preferentially to injured tissue, where they secrete opioids to reduce pain. Investigation of the mechanisms underlying the migration of opioid-containing immune cells to inflamed tissue is an active area of research, with recent data demonstrating the importance of cell adhesion molecules in leukocyte adhesion to both the endothelium in vascular transmigration and to neurons within peripheral inflamed tissue. This review summarizes the physiological mechanisms and clinical significance of this unique endogenous peripheral analgesic pathway and discusses therapeutic implications for the development of novel targeted peripheral analgesics. Copyright 2010 Elsevier Ltd. All rights reserved.

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.

Graduate admissions in clinical neuropsychology: the importance of undergraduate training.

PubMed

Karazsia, Bryan T; Stavnezer, Amy Jo; Reeves, Jonathan W

2013-11-01

Discussions of and recommendations for the training of clinical neuropsychologists exist at the doctoral, internship, and post-doctoral level. With few exceptions, the literature on undergraduate preparations in clinical neuropsychology is sparse and lacks empirical evidence. In the present study, graduate-level faculty and current trainees completed surveys about graduate school preparations. Faculty expectations of minimum and ideal undergraduate training were highest for research methods, statistics, and assessment. Preferences for "goodness of fit" also emerged as important admissions factors. These results offer evidence for desirable undergraduate preparations for advanced study in clinical neuropsychology. Although undergraduate training in psychology is intentionally broad, results from this study suggest that students who desire advanced study in clinical neuropsychology need to tailor their experiences to be competitive in the application process. The findings have implications for prospective graduate students, faculty who train and mentor undergraduates, and faculty who serve on admissions committees.

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.

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.

UNMASKING MASKED HYPERTENSION: PREVALENCE, CLINICAL IMPLICATIONS, DIAGNOSIS, CORRELATES, AND FUTURE DIRECTIONS

PubMed Central

Peacock, James; Diaz, Keith M.; Viera, Anthony J.; Schwartz, Joseph E.; Shimbo, Daichi

2014-01-01

‘Masked hypertension’ is defined as having non-elevated clinic blood pressure (BP) with elevated out-of-clinic average BP, typically determined by ambulatory BP monitoring. Approximately 15–30% of adults with non-elevated clinic BP have masked hypertension. Masked hypertension is associated with increased risks of cardiovascular morbidity and mortality compared to sustained normotension (non-elevated clinic and ambulatory BP), which is similar to or approaching the risk associated with sustained hypertension (elevated clinic and ambulatory BP). The confluence of increased cardiovascular risk and a failure to be diagnosed by the conventional approach of clinic BP measurement makes masked hypertension a significant public health concern. However, many important questions remain. First, the definition of masked hypertension varies across studies. Further, the best approach in the clinical setting to exclude masked hypertension also remains unknown. It is unclear whether home BP monitoring is an adequate substitute for ambulatory BP monitoring in identifying masked hypertension. Few studies have examined the mechanistic pathways that may explain masked hypertension. Finally, scarce data are available on the best approach to treating individuals with masked hypertension. Herein, we review the current literature on masked hypertension including definition, prevalence, clinical implications, special patient populations, correlates, issues related to diagnosis, treatment, and areas for future research. PMID:24573133

How to Develop a Cardio-Oncology Clinic.

PubMed

Snipelisky, David; Park, Jae Yoon; Lerman, Amir; Mulvagh, Sharon; Lin, Grace; Pereira, Naveen; Rodriguez-Porcel, Martin; Villarraga, Hector R; Herrmann, Joerg

2017-04-01

Cardiovascular demands to the care of cancer patients are common and important given the implications for morbidity and mortality. As a consequence, interactions with cardiovascular disease specialists have intensified to the point of the development of a new discipline termed cardio-oncology. As an additional consequence, so-called cardio-oncology clinics have emerged, in most cases staffed by cardiologists with an interest in the field. This article addresses this gap and summarizes key points in the development of a cardio-oncology clinic. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Ultrasound and Microbubble Guided Drug Delivery: Mechanistic Understanding and Clinical Implications

PubMed Central

Wang, Tzu-Yin; Wilson, Katheryne E.; Machtaler, Steven; Willmann, Jürgen K.

2014-01-01

Ultrasound mediated drug delivery using microbubbles is a safe and noninvasive approach for spatially localized drug administration. This approach can create temporary and reversible openings on cellular membranes and vessel walls (a process called “sonoporation”), allowing for enhanced transport of therapeutic agents across these natural barriers. It is generally believed that the sonoporation process is highly associated with the energetic cavitation activities (volumetric expansion, contraction, fragmentation, and collapse) of the microbubble. However, a thorough understanding of the process was unavailable until recently. Important progress on the mechanistic understanding of sonoporation and the corresponding physiological responses in vitro and in vivo has been made. Specifically, recent research shed light on the cavitation process of microbubbles and fluid motion during insonation of ultrasound, on the spatio-temporal interactions between microbubbles and cells or vessel walls, as well as on the temporal course of the subsequent biological effects. These findings have significant clinical implications on the development of optimal treatment strategies for effective drug delivery. In this article, current progress in the mechanistic understanding of ultrasound and microbubble mediated drug delivery and its implications for clinical translation is discussed. PMID:24372231

Discriminating cognitive screening and cognitive testing from neuropsychological assessment: implications for professional practice.

PubMed

Block, Cady K; Johnson-Greene, Doug; Pliskin, Neil; Boake, Corwin

2017-04-01

To provide clarification on the distinction between cognitive screening, cognitive testing, and neuropsychological assessment and highlight practical implications. Non-systematic brief clinical review. There is a present lack of explicit distinction between the various levels of measurement of cognitive functioning with regard to goals, indications for use, levels of complexity, and outcome. There is also a lack of guidance regarding the identification of who should be responsible for the administration and interpretation at each level. There is a growing awareness of the importance of cognitive health and disability, and of the importance of measurement of cognitive functions across the lifespan. For example, cognitive screening has been mandated by the Patient Protection and Affordable Care Act of 2010, and language contained within new psychiatric diagnostic criteria and healthcare regulatory changes reflect increased consideration of the importance of measurement of cognition. Changes such as these necessitate greater clarity on this important issue as it bears implications for professional practice, which ranges from education and training competencies, practice standards, and the way that neuropsychologists clarify and advocate for the value of specialty referrals for comprehensive assessment in a competitive and ever-changing healthcare market.

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.

Phonological Awareness Training and Short-Term Working Memory: Clinical Implications.

ERIC Educational Resources Information Center

Gillam, Ronald B.; van Kleeck, Anne

1996-01-01

This article finds that two aspects of phonological working memory, phonological coding and phonological recoding, appear to be important elements in the relationship between phonological working memory and phonological awareness. It suggests an approach to training in phonological awareness and reports an intervention study in which phonological…

Recurrent Guillain-Barré syndrome presenting stereotypic manifestations, positive antiganglioside antibodies, and rapid recovery.

PubMed

Pyun, So Young; Jeong, Jin-Ho; Bae, Jong Seok

2015-12-01

Recurrent Guillain-Barré syndrome (rGBS) has been described as a rare entity with distinct characteristics. However, little is known about rGBS in Asian group. The aim of this study was to identify the incidence and clinical course of rGBS, and to determine its clinical/pathophysiological implications. The consecutive data of 117 GBS patients were retrieved from a single university-based hospital in Korea and analyzed in terms of clinical, serological, electrophysiological aspects. A thorough review revealed that three (2.6%) of the enrolled patients had experienced more than two definite recurrent attacks of GBS. Interestingly, all three cases exhibited clinically stereotypical features, serum antiganglioside antibodies, and rapid recovery after intravenous immunoglobulin treatment. Clinical, serological, and electrophysiological features of rGBS cases were described in detail. The stereotypic presentation of each attack in this variant suggests the importance of both host and genetic factors for the clinical manifestations. In addition, the simultaneous presence of serum antiganglioside antibodies and rapid recovery implicate reversible nerve conduction failure as the mechanism of rGBS. These features are different from typical monophasic GBS and acute onset of chronic inflammatory demyelinating polyneuropathy. Copyright © 2015 Elsevier B.V. All rights reserved.

Values in health care professional socialization: implications for geriatric education in interdisciplinary teamwork.

PubMed

Clark, P G

1997-08-01

The development of an identity and pattern of practice in the health care professions is based on a process of socialization into the roles and norms of a particular discipline and has important implications for clinical practice with elderly persons. Presented is a model for understanding the socialization process of physicians, nurses, and social workers as the development of professional meaning ("voice") based on the acquisition of value orientations or themes intrinsic to their education and training. The implications of these patterns for the abilities of different professions to work together collaboratively in the care of older persons are highlighted as a framework for developing new interdisciplinary curricular models in gerontological and geriatric education.

HDGF: a novel jack-of-all-trades in cancer.

PubMed

Bao, Cihang; Wang, Jianbo; Ma, Wei; Wang, Xintong; Cheng, Yufeng

2014-12-01

HDGF is an important regulator of a broad range of cancer cell activities and plays important roles in cancer cell transformation, apoptosis, angiogenesis and metastasis. Such a divergent influence of HDGF on cancer cell activities derives from its multiple inter- and sub-cellular localizations where it interacts with a range of different binding partners. Interestingly, high levels of HDGF could be detected in patients' serum of some cancers. This review is focused on the role of HDGF in tumorigenesis and metastasis, and provides insight for application in clinical cancer therapy as well as its clinical implications as a prognostic marker in cancer progression.

A new face for private providers in developing countries: what implications for public health?

PubMed

Palmer, Natasha; Mills, Anne; Wadee, Haroon; Gilson, Lucy; Schneider, Helen

2003-01-01

The use of private health care providers in low- and middle-income countries (LMICs) is widespread and is the subject of considerable debate. We review here a new model of private primary care provision emerging in South Africa, in which commercial companies provide standardized primary care services at relatively low cost. The structure and operation of one such company is described, and features of service delivery are compared with the most probable alternatives: a private general practitioner or a public sector clinic. In a case study of cost and quality of services, the clinics were popular with service users and run at a cost per visit comparable to public sector primary care clinics. However, their current role in tackling important public health problems was limited. The implications for public health policy of the emergence of this new model of private provider are discussed. It is argued that encouraging the use of such clinics by those who can afford to pay for them might not help to improve care available for the poorest population groups, which are an important priority for the government. Encouraging such providers to compete for government funding could, however, be desirable if the range of services presently offered, and those able to access them, could be broadened. However, the constraints to implementing such a system successfully are notable, and these are acknowledged. Even without such contractual arrangements, these companies provide an important lesson to the public sector that acceptability of services to users and low-cost service delivery are not incompatible objectives.

A new face for private providers in developing countries: what implications for public health?

PubMed Central

Palmer, Natasha; Mills, Anne; Wadee, Haroon; Gilson, Lucy; Schneider, Helen

2003-01-01

The use of private health care providers in low- and middle-income countries (LMICs) is widespread and is the subject of considerable debate. We review here a new model of private primary care provision emerging in South Africa, in which commercial companies provide standardized primary care services at relatively low cost. The structure and operation of one such company is described, and features of service delivery are compared with the most probable alternatives: a private general practitioner or a public sector clinic. In a case study of cost and quality of services, the clinics were popular with service users and run at a cost per visit comparable to public sector primary care clinics. However, their current role in tackling important public health problems was limited. The implications for public health policy of the emergence of this new model of private provider are discussed. It is argued that encouraging the use of such clinics by those who can afford to pay for them might not help to improve care available for the poorest population groups, which are an important priority for the government. Encouraging such providers to compete for government funding could, however, be desirable if the range of services presently offered, and those able to access them, could be broadened. However, the constraints to implementing such a system successfully are notable, and these are acknowledged. Even without such contractual arrangements, these companies provide an important lesson to the public sector that acceptability of services to users and low-cost service delivery are not incompatible objectives. PMID:12764496

Transparency in the reporting of in vivo pre-clinical pain research: The relevance and implications of the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines.

PubMed

Rice, Andrew S C; Morland, Rosemary; Huang, Wenlong; Currie, Gillian L; Sena, Emily S; Macleod, Malcolm R

2017-12-29

Clear reporting of research is crucial to the scientific process. Poorly designed and reported studies are damaging not only to the efforts of individual researchers, but also to science as a whole. Standardised reporting methods, such as those already established for reporting randomised clinical trials, have led to improved study design and facilitated the processes of clinical systematic review and meta-analysis. Such standards were lacking in the pre-clinical field until the development of the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines. These were prompted following a survey which highlighted a widespread lack of robust and consistent reporting of pre-clinical in vivo research, with reports frequently omitting basic information required for study replication and quality assessment. The resulting twenty item checklist in ARRIVE covers all aspects of experimental design with particular emphasis on bias reduction and methodological transparency. Influential publishers and research funders have already adopted ARRIVE. Further dissemination and acknowledgement of the importance of these guidelines is vital to their widespread implementation. Conclusions and implications Wide implementation of the ARRIVE guidelines for reporting of in vivo preclinical research, especially pain research, are essential for a much needed increased transparency and quality in publishing such research. ARRIVE will also positively influence improvements in experimental design and quality, assist the conduct of accurate replication studies of important new findings and facilitate meta-analyses of preclinical research.

On the status of knowledge for using punishment implications for treating behavior disorders.

PubMed Central

Lerman, Dorothea C; Vorndran, Christina M

2002-01-01

In this paper, we review basic and applied findings on punishment and discuss the importance of conducting further research in this area. The characteristics of responding during punishment and numerous factors that interact with basic processes are delineated in conjunction with implications for the treatment of behavior disorders in clinical populations. We conclude that further understanding of punishment processes is needed to develop a highly systematic, effective technology of behavior change, including strategies for improving the efficacy of less intrusive procedures and for successfully fading treatment. PMID:12555918

Beyond Positivism: Understanding and addressing childhood obesity disparities through a Critical Theory perspective

PubMed Central

Schroeder, Krista; Kulage, Kristine M.; Lucero, Robert

2016-01-01

Purpose We apply Critical Theory to examine menu labeling with the aim of uncovering important implications for nursing practice, research, and policy. Conclusions Our critical analysis uncovers barriers to menu labeling's effectiveness, particularly for vulnerable populations. Nurses must work to minimize the impact of these barriers and optimize the effectiveness of menu labeling, in order to strengthen the fight against obesity. Practice implications We suggest changes, guided by this critical analysis,that can be implemented by nurses working in clinical practice, research, and policy. PMID:26112774

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.

Non-specific effects of vaccines: plausible and potentially important, but implications uncertain.

PubMed

Pollard, Andrew J; Finn, Adam; Curtis, Nigel

2017-11-01

Non-specific effects (NSE) or heterologous effects of vaccines are proposed to explain observations in some studies that certain vaccines have an impact beyond the direct protection against infection with the specific pathogen for which the vaccines were designed. The importance and implications of such effects remain controversial. There are several known immunological mechanisms which could lead to NSE, since it is widely recognised that the generation of specific immunity is initiated by non-specific innate immune mechanisms that may also have wider effects on adaptive immune function. However, there are no published studies that demonstrate a mechanistic link between such immunological phenomena and clinically relevant NSE in humans. While it is highly plausible that some vaccines do have NSE, their magnitude and duration, and thus importance, remain uncertain. Although the WHO recently concluded that current evidence does not justify changes to immunisation policy, further studies of sufficient size and quality are needed to assess the importance of NSE for all-cause mortality. This could provide insights into vaccine immunobiology with important implications for infant health and survival. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A brief survey of aquaporins and their implications for renal physiology.

PubMed

Gade, Wayne; Robinson, Brooke

2006-01-01

Aquaporins (AQPs) are an important family of proteins that efficiently channel water through the cell membranes. Although water can diffuse across biological membranes at measurable rates, physiologists had long predicted the existence of channels to facilitate rapid reabsorption of water by renal tubular cells. With AQPs present, water can "gush" through the membrane at the extraordinary rate of three billion water molecules per second per aquaporin channel. In their absence, water only trickles across the hydrophobic lipid bilayers of cell membranes. Aquaporins have fascinated researchers over the last decade, culminating in the 2003 Nobel Prize for Chemistry given to their discoverer, Dr. Peter Agre. During the 1990s, scientists identified and characterized members of the mammalian aquaporin family, now designated as AQP0 through AQP10. AQPs are also found in many plant and bacterial species. However, their relevance to the clinical laboratory is only recently emerging. Dr. Agre's Nobel symposium address provides an excellent mini-review of aquaporins in medicine. Our understanding of renal physiology and pathophysiology has advanced greatly as we account for the subtle implications of various AQP systems. For example, nephrogenic diabetes insipidus (NDI), the inability to produce concentrated urine, can result from several different malfunctions in the AQP2 system controlled by anti-diuretic hormone (ADH). Virtually all mammalian cells incorporate aquaporins into their cell membranes, and many cells produce multiple aquaporins, each with a specific function. It is therefore not surprising that malfunctions have important clinical conditions. The present article discusses the implications of aquaporins for renal physiology, while the accompanying article is focused on the clinical aspects of aquaporins.

Erognomic education on housework for women with upper limb repetitive strain injury (RSI): a conceptual representation of therapists' clinical reasoning.

PubMed

Cheung, Therma W C; Clemson, Lindy; O' Loughlin, Kate; Shuttleworth, Russell

2017-09-18

Ergonomic education in housework that aims to facilitate behavior change is important for women with upper limb repetitive strain injury. Therapists usually conduct such programs based on implicit reasoning. Making this reasoning explicit is important in contributing to the profession's knowledge. To construct a conceptual representation of how occupational therapists make clinical decisions for such program. Based on a constructivist-grounded theory methodology, data were collected through in-depth interviewing with 14 occupational therapists from a major hospital in Singapore. Interviews were audiotaped and transcribed. Data was analyzed with line by line, focused and axial coding with constant data comparison throughout data collection. Therapists made clinical decisions based on their perceptions of their clients' behavior change in three stages: (i) listen; (ii) try; and (iii) persevere, bearing significant similarities to the transtheoretical theory of change. The study also showed that therapists may not have considered the full range of meanings that their clients attach to housework when interacting with them, a gap that needs to be addressed. The present study indicates the importance of therapists' understanding of the meanings that their clients attach to housework. Further research needs to address how to achieve this in a time-pressured clinical environment. Implications for Rehabilitation This study used qualitative research to demonstrate the process of translating therapists' tacit knowledge into an explicit form. It elucidates the following major implications for practice when therapists conduct ergonomic education to facilitate behavior change in housework for female homemakers with upper limb RSI:The conceptual framework of clinical reasoning constructed from the results can be used to increase therapists' awareness of how they make clinical decisions during an intervention. This framework can also be used for training new therapists. It is important for therapists to actively listen to their clients. Active listening will enable the therapists to understand and consider the personal meanings that these women attach to housework in order to facilitate a behavior change. Client-therapist interactions to facilitate clients' willingness to change should become a major focus in such a program. Similar research should be conducted in other clinical areas to develop explicit clinical reasoning frameworks to facilitate learning of novice therapists and reflection of experienced therapists to address any gap in their clinical reasoning.

Lymph node metastasis in melanoma: a debate on the significance of nodal metastases, conditional survival analysis and clinical trials.

PubMed

Faries, Mark B; Han, Dale; Reintgen, Michael; Kerivan, Lauren; Reintgen, Douglas; Caracò, Corrado

2018-05-18

While there is no doubt that regional lymph node metastases are an enormously important factor in melanoma staging and treatment, the biology behind this significance and its precise implications for treatment planning have been a leading controversy in melanoma and other solid tumors for over a century. Recent clinical data, including data from prospective randomized clinical trials have refined our understanding of the process of nodal metastases and the advantages and disadvantages of different clinical management strategies. This review presents two points of view in this debate and discusses the results of new data analyses as well as pivotal clinical trials informing the discussion.

Clinical and scientific importance of source control in abdominal infections: summary of a symposium

PubMed Central

Bohnen, John M.A.; Marshall, John C.; Fry, Donald E.; Johnson, Steven B.; Solomkin, Joseph S.

1999-01-01

In May 1997, a panel of surgeon-investigators met to discuss the clinical importance and research implications of controlling the source of abdominal infections. It was concluded that source control is critical to therapeutic success and that antimicrobial therapy and other adjunctive interventions will fail if the source of infection is not controlled by resection, exteriorization or other means. The panelists presented different definitions of source control, depending on the scientific purpose of the definition. All participants agreed that failure to consider the adequacy of source control of infection has limited the value of most clinical trials of therapeutic anti-infective agents. Besides recognizing source control as an essential goal of patient care, the panelists emphasized the need for further investigative work to define, record and stratify the adequacy of source control in clinical trials of therapeutic agents for abdominal infections. PMID:10223073

Occurrence of spvA Virulence Gene and Clinical Significance for Multidrug-Resistant Salmonella Strains ▿

PubMed Central

Gebreyes, Wondwossen A.; Thakur, Siddhartha; Dorr, Paul; Tadesse, Daniel A.; Post, Karen; Wolf, Leslie

2009-01-01

Nontyphoidal Salmonella strains are important reservoirs of antimicrobial resistance. An important issue that has not been investigated is whether the multiresistant Salmonella strains are more virulent than their susceptible counterparts. Salmonella isolates collected from clinical human (n = 888) and porcine (n = 2,120) cases at the same time period and geographic location were investigated. Antimicrobial susceptibility, PCR analysis for the spvA virulence gene, and pulsed-field gel electrophoresis (PFGE) genotyping were done. Carriage of spvA was associated with multidrug-resistant (MDR) type ACSSuT strains (odds ratio, 7.1; P < 0.05), a type often implicated in bacteremic human cases. PFGE revealed that clinical isolates from pigs were more clonally related to those of human origin than the nonclinical porcine isolates. The findings suggest that MDR strains that also carry specific virulence factors are more likely to be of clinical significance. PMID:19116354

A survey of UK fertility clinics' approach to surrogacy arrangements.

PubMed

Norton, Wendy; Crawshaw, Marilyn; Hudson, Nicky; Culley, Lorraine; Law, Caroline

2015-09-01

This paper draws on the findings of the first survey of surrogacy arrangements in Human Fertilisation and Embryology Authority (HFEA) licensed fertility clinics since 1998. Given the complex social, ethical and legal issues involved, surrogacy continues to raise debate worldwide and fuel calls for increased domestic provision in developed countries. However, little is known about how recent changes have affected HFEA licensed clinics. A 24-item online survey was undertaken between August and October 2013, designed to improve understanding of recent trends and current practices associated with UK-based surrogacy, and consider the implications for future policy and practice in UK and cross-border surrogacy arrangements. The response rate was 51.4%, comprising 54 clinics. Quantitative data were analysed using descriptive statistics, and open-ended qualitative responses analysed for extending understanding. Of the participating clinics, 42.6% offered surrogacy (mostly gestational surrogacy). Heterosexual couples using gestational surrogacy were the largest group currently using services followed by male same-sex couples. Most clinics reported having encountered problems with surrogacy treatments, suggesting barriers still exist to expanding the UK provision of surrogacy arrangements. It is important that professionals are well informed about the legal implications of surrogacy and that clinics have consistent and appropriate operational protocols for surrogacy arrangements. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Transforming long-term care pain management in north america: the policy-clinical interface.

PubMed

Hadjistavropoulos, Thomas; Marchildon, Gregory P; Fine, Perry G; Herr, Keela; Palley, Howard A; Kaasalainen, Sharon; Béland, François

2009-04-01

The undertreatment of pain in older adults who reside in long-term care (LTC) facilities has been well documented, leading to clinical guideline development and professional educational programs designed to foster better pain assessment and management in this population. Despite these efforts, little improvement has occurred, and we postulate that focused attention to public policy and cost implications of systemic change is required to create positive pain-related outcomes. Our goal was to outline feasible and cost-effective clinical and public policy recommendations designed to address the undermanagement of pain in LTC facilities. We arranged a 2-day consensus meeting of prominent United States and Canadian pain and public policy experts. An initial document describing the problem of pain undermanagement in LTC was developed and circulated prior to the meeting. Participants were also asked to respond to a list of relevant questions before arriving. Following formal presentations of a variety of proposals and extensive discussion among clinicians and policy experts, a set of recommendations was developed. We outline key elements of a transformational model of pain management in LTC for the United States and Canada. Consistent with previously formulated clinical guidelines but with attention to readily implementable public policy change in both countries, this transformational model of LTC has important implications for LTC managers and policy makers as well as major quality of life implications for LTC residents.

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.

The Forms and Functions of Impulsive Actions: Implications for Behavioral Assessment and Therapy

ERIC Educational Resources Information Center

Farmer, Richard F.; Golden, Jeannie A.

2009-01-01

Impulsivity is a central defining feature of several psychiatric disorders and a frequent correlate of many forms of psychopathology and maladjustment. Despite recognition of the importance of impulsivity to an understanding of a wide variety of clinically-relevant behaviors, this multifaceted construct remains ill-defined and not well understood.…

The Relations among Measurements of Informant Discrepancies within a Multisite Trial of Treatments for Childhood Social Phobia

ERIC Educational Resources Information Center

De Los Reyes, Andres; Alfano, Candice A.; Beidel, Deborah C.

2010-01-01

Discrepancies between informants' reports of children's behavior are robustly observed in clinical child research and have important implications for interpreting the outcomes of controlled treatment trials. However, little is known about the basic psychometric properties of these discrepancies. This study examined the relation between…

Methodological Issues and Practical Strategies in Research on Child Maltreatment Victims' Abilities and Experiences as Witnesses

ERIC Educational Resources Information Center

Chae, Yoojin; Goodman, Gail S.; Bederian-Gardner, Daniel; Lindsay, Adam

2011-01-01

Scientific studies of child maltreatment victims' memory abilities and court experiences have important legal, psychological, and clinical implications. However, state-of-the-art research on child witnesses is often hindered by methodological challenges. In this paper, we address specific problems investigators may encounter when attempting such…

Taxometric Analyses of Specific Language Impairment in 3- And 4-Year-Old Children.

ERIC Educational Resources Information Center

Dollaghan, Christine A.

2004-01-01

Specific language impairment (SLI), like many diagnostic labels for complex behavioral conditions, is often assumed to define a category of children who differ not only in degree but also in kind from children developing language normally. Although this assumption has important implications for theoretical models and clinical approaches, its…

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.

Accuracy of clinical coding for procedures in oral and maxillofacial surgery.

PubMed

Khurram, S A; Warner, C; Henry, A M; Kumar, A; Mohammed-Ali, R I

2016-10-01

Clinical coding has important financial implications, and discrepancies in the assigned codes can directly affect the funding of a department and hospital. Over the last few years, numerous oversights have been noticed in the coding of oral and maxillofacial (OMF) procedures. To establish the accuracy and completeness of coding, we retrospectively analysed the records of patients during two time periods: March to May 2009 (324 patients), and January to March 2014 (200 patients). Two investigators independently collected and analysed the data to ensure accuracy and remove bias. A large proportion of operations were not assigned all the relevant codes, and only 32% - 33% were correct in both cycles. To our knowledge, this is the first reported audit of clinical coding in OMFS, and it highlights serious shortcomings that have substantial financial implications. Better input by the surgical team and improved communication between the surgical and coding departments will improve accuracy. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

An integrated model of clinical reasoning: dual-process theory of cognition and metacognition.

PubMed

Marcum, James A

2012-10-01

Clinical reasoning is an important component for providing quality medical care. The aim of the present paper is to develop a model of clinical reasoning that integrates both the non-analytic and analytic processes of cognition, along with metacognition. The dual-process theory of cognition (system 1 non-analytic and system 2 analytic processes) and the metacognition theory are used to develop an integrated model of clinical reasoning. In the proposed model, clinical reasoning begins with system 1 processes in which the clinician assesses a patient's presenting symptoms, as well as other clinical evidence, to arrive at a differential diagnosis. Additional clinical evidence, if necessary, is acquired and analysed utilizing system 2 processes to assess the differential diagnosis, until a clinical decision is made diagnosing the patient's illness and then how best to proceed therapeutically. Importantly, the outcome of these processes feeds back, in terms of metacognition's monitoring function, either to reinforce or to alter cognitive processes, which, in turn, enhances synergistically the clinician's ability to reason quickly and accurately in future consultations. The proposed integrated model has distinct advantages over other models proposed in the literature for explicating clinical reasoning. Moreover, it has important implications for addressing the paradoxical relationship between experience and expertise, as well as for designing a curriculum to teach clinical reasoning skills. © 2012 Blackwell Publishing Ltd.

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

Considerations in pharmaceutical conversion: focus on antihistamines.

PubMed

Garbus, S B; Moulton, B W; Meltzer, E O; Reich, P R; Weinreb, L F; Friedman, J A; Orland, B I

1997-04-01

The practice of pharmaceutical conversion, which encompasses three types of drug interchange (generic, brand, and therapeutic substitution), is increasing in managed care settings. Pharmaceutical conversion has numerous implications for managed care organizations, their healthcare providers, and their customers. Although drug cost may be a driving consideration in pharmaceutical conversion, a number of other considerations are of equal or greater importance in the decision-making process may affect the overall cost of patient care. Among these considerations are clinical, psychosocial, and safety issues; patient adherence; patient satisfaction; and legal implications of pharmaceutical conversion. Patient-centered care must always remain central to decisions about pharmaceutical conversion. This article discusses the issues related to, and implications of, pharmaceutical conversion utilizing the antihistamines class of drugs as the case situation.

Prolactin secretion patterns: basic mechanisms and clinical implications for reproduction.

PubMed

Egli, Marcel; Leeners, Brigitte; Kruger, Tillmann H C

2010-11-01

Prolactin (PRL) is one of the most versatile hormones in the mammalian body affecting reproductive, sexual, metabolic, immune, and other functions. It is therefore not surprising that the neural control of PRL secretion is complex, involving the coordinated actions of several hypothalamic nuclei. A plethora of experimental data exists on the hypothalamic control of hormone secretion under various physiological stimuli. There have been even mathematical models and computer studies published, which help to understand the complex hypothalamic-pituitary network. Nevertheless, the putative role of PRL for human reproduction still has to be clarified. Here, we review data on the underlying mechanisms controlling PRL secretion using both experimental and mathematical approaches. These investigations primarily focus on rhythmic secretion in rats during early pregnancy or pseudopregnancy, and they point to the important role of oxytocin as a crucial PRL-releasing factor. Recent data on human studies and their theoretical and clinical implications are reviewed as well. In particular, studies demonstrating a sustained PRL surge after sexual climax in males and females are presented, indicating possible implications for both sexual satiation and reproductive functions. Taking these data together, there is evidence for the hypothesis that the PRL surge induced by sexual activity, together with the altered PRL rhythmic pattern, is important for successful initialization of pregnancy not only in rodents but also possibly in humans. However, further investigations are needed to clarify such a role in humans.

Application of legal principles and medical ethics: multifetal pregnancy and fetal reduction

PubMed Central

Cheong, May Anne; Tay, Catherine Swee Kian

2014-01-01

In the management of complex medical cases such as a multifetal pregnancy, knowledge of the ethical and legal implications is important, alongside having competent medical skills. This article reviews these principles and applies them to scenarios of multifetal pregnancy and fetal reduction. Such a discussion is not solely theoretical, but is also relevant to clinical practice. The importance of topics such as bioethical principles and informed consent are also herein addressed. PMID:25017403

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

Osteogenesis imperfecta types I-XI: implications for the neonatal nurse.

PubMed

Womack, Jody

2014-10-01

Osteogenesis imperfecta (OI), also called "brittle bone disease," is a rare heterozygous connective tissue disorder that is caused by mutations of genes that affect collagen. Osteogenesis imperfecta is characterized by decreased bone mass, bone fragility, and skin hyperlaxity. The phenotype present is determined according to the mutation on the affected gene as well as the type and location of the mutation. Osteogenesis imperfecta is neither preventable nor treatable. Osteogenesis imperfecta is classified into 11 types to date, on the basis of their clinical symptoms and genetic components. This article discusses the definition of the disease, the classifications on the basis of its clinical features, incidence, etiology, and pathogenesis. In addition, phenotype, natural history, diagnosis and management of this disease, recurrence risk, and, most importantly, the implications for the neonatal nurse and management for the family are discussed.

"There are too many, but never enough": qualitative case study investigating routine coding of clinical information in depression.

PubMed

Cresswell, Kathrin; Morrison, Zoe; Kalra, Dipak; Sheikh, Aziz

2012-01-01

We sought to understand how clinical information relating to the management of depression is routinely coded in different clinical settings and the perspectives of and implications for different stakeholders with a view to understanding how these may be aligned. Qualitative investigation exploring the views of a purposefully selected range of healthcare professionals, managers, and clinical coders spanning primary and secondary care. Our dataset comprised 28 semi-structured interviews, a focus group, documents relating to clinical coding standards and participant observation of clinical coding activities. We identified a range of approaches to coding clinical information including templates and order entry systems. The challenges inherent in clearly establishing a diagnosis, identifying appropriate clinical codes and possible implications of diagnoses for patients were particularly prominent in primary care. Although a range of managerial and research benefits were identified, there were no direct benefits from coded clinical data for patients or professionals. Secondary care staff emphasized the role of clinical coders in ensuring data quality, which was at odds with the policy drive to increase real-time clinical coding. There was overall no evidence of clear-cut direct patient care benefits to inform immediate care decisions, even in primary care where data on patients with depression were more extensively coded. A number of important secondary uses were recognized by healthcare staff, but the coding of clinical data to serve these ends was often poorly aligned with clinical practice and patient-centered considerations. The current international drive to encourage clinical coding by healthcare professionals during the clinical encounter may need to be critically examined.

A critical evaluation of the validity of episodic future thinking: A clinical neuropsychology perspective.

PubMed

Ward, Amanda M

2016-11-01

Episodic future thinking is defined as the ability to mentally simulate a future event. Although episodic future thinking has been studied extensively in neuroscience, this construct has not been explored in depth from the perspective of clinical neuropsychology. The aim of this critical narrative review is to assess the validity and clinical implications of episodic future thinking. A systematic review of episodic future thinking literature was conducted. PubMed and PsycInfo were searched through July 2015 for review and empirical articles with the following search terms: "episodic future thinking," "future mental simulation," "imagining the future," "imagining new experiences," "future mental time travel," "future autobiographical experience," and "prospection." The review discusses evidence that episodic future thinking is important for adaptive functioning, which has implications for neurological populations. To determine the validity of episodic future thinking, the construct is evaluated with respect to related constructs, such as imagination, episodic memory, autobiographical memory, prospective memory, narrative construction, and working memory. Although it has been minimally investigated, there is evidence of convergent and discriminant validity for episodic future thinking. Research has not addressed the incremental validity of episodic future thinking. Practical considerations of episodic future thinking tasks and related constructs in a clinical neuropsychological setting are considered. The utility of episodic future thinking is currently unknown due to the lack of research investigating the validity of episodic future thinking. Future work is discussed, which could determine whether episodic future thinking is an important missing piece in standard clinical neuropsychological assessment. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The Genetics of Autism: Key Issues, Recent Findings and Clinical Implications

PubMed Central

El-Fishawy, Paul; State, Matthew W.

2010-01-01

Autism spectrum disorders (ASD’S) are highly heritable. Consequently, gene discovery promises to help illuminate the pathophysiology of these syndromes, yielding important opportunities for the development of novel treatments and a more nuanced understanding of the natural history of these disorders. Although the underlying genetic architecture of ASD’s is not yet known, the literature demonstrates that it is not, writ large, a monogenic disorder with Mendelian inheritance, but rather a group of complex genetic syndromes with risk deriving from genetic variations in multiple genes. The widely accepted “Common Disease-Common Variant” hypothesis predicts that the risk alleles in ASD’s and other complex disorders will be common in the general population. However, recent evidence from gene discovery efforts in a wide range of diseases raises important questions regarding the overall applicability of the theory and the extent of its usefulness in explaining individual genetic liability. In contrast, considerable evidence points to the importance of rare alleles both with regard to their value in providing a foothold into the molecular mechanisms of ASD and their overall contribution to the population-wide risk. This chapter reviews the origins of the common versus rare variant debate, highlights recent findings in the field, and addresses the clinical implications of both common and rare variant discoveries. PMID:20159341

Reflections on Klein's radical notion of phantasy and its implications for analytic practice.

PubMed

Blass, Rachel B

2017-06-01

Analysts may incorporate many of Melanie Klein's important contributions (e.g., on preoedipal dynamics, envy, and projective identification) without transforming their basic analytic approach. In this paper I argue that adopting the Kleinian notion of unconscious phantasy is transformative. While it is grounded in Freud's thinking and draws out something essential to his work, this notion of phantasy introduces a radical change that defines Kleinian thinking and practice and significantly impacts the analyst's basic clinical approach. This impact and its technical implications in the analytic situation are illustrated and discussed. Copyright © 2017 Institute of Psychoanalysis.

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

Molecular genetics made simple

PubMed Central

Kassem, Heba Sh.; Girolami, Francesca; Sanoudou, Despina

2012-01-01

Abstract Genetics have undoubtedly become an integral part of biomedical science and clinical practice, with important implications in deciphering disease pathogenesis and progression, identifying diagnostic and prognostic markers, as well as designing better targeted treatments. The exponential growth of our understanding of different genetic concepts is paralleled by a growing list of genetic terminology that can easily intimidate the unfamiliar reader. Rendering genetics incomprehensible to the clinician however, defeats the very essence of genetic research: its utilization for combating disease and improving quality of life. Herein we attempt to correct this notion by presenting the basic genetic concepts along with their usefulness in the cardiology clinic. Bringing genetics closer to the clinician will enable its harmonious incorporation into clinical care, thus not only restoring our perception of its simple and elegant nature, but importantly ensuring the maximal benefit for our patients. PMID:25610837

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

Gaze perception in social anxiety and social anxiety disorder

PubMed Central

Schulze, Lars; Renneberg, Babette; Lobmaier, Janek S.

2013-01-01

Clinical observations suggest abnormal gaze perception to be an important indicator of social anxiety disorder (SAD). Experimental research has yet paid relatively little attention to the study of gaze perception in SAD. In this article we first discuss gaze perception in healthy human beings before reviewing self-referential and threat-related biases of gaze perception in clinical and non-clinical socially anxious samples. Relative to controls, socially anxious individuals exhibit an enhanced self-directed perception of gaze directions and demonstrate a pronounced fear of direct eye contact, though findings are less consistent regarding the avoidance of mutual gaze in SAD. Prospects for future research and clinical implications are discussed. PMID:24379776

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.

Clinical psychology and disability studies: bridging the disciplinary divide on mental health and disability.

PubMed

Simpson, Jane; Thomas, Carol

2015-01-01

Clinical psychology and disability studies have traditionally occupied very different academic, philosophical and political spaces. However, this paper aims to illustrate the positive consequences and implications of attempts to understand and bridge this disciplinary divide. A narrative review format was used with evidence selected pragmatically as opposed to systematically. The construction of the argument determined the evidence selected. The concept of psycho-emotional disablism, which originated within disability studies, is argued to be a useful concept to bridge the divide between understandings of distress from both disability studies and clinical psychology perspectives. However, this can be usefully augmented by psychological research on the mechanisms through which disablism can affect individuals. Perspectives from both disability studies and clinical psychology can be usefully combined to bring important new perspectives; combined, these perspectives should help - on theoretical, service and social levels - to improve the mental health of disabled people. Implications for Rehabilitation Mental health is an important determinant of overall health-related quality of life and psychological therapy should be available for those disabled people who would value it. Psychological therapists working with disabled people should be more aware of the challenging social context in which disabled people live. Understandings of distress should not just include individual factors but also incorporate the psychological impact of stresses caused by societal barriers preventing inclusion. Psychologists should be more willing to work and engage at a societal and political level to influence change.

An Opportunity to Bridge the Gap Between Clinical Research and Clinical Practice: Implications for Clinical Training

PubMed Central

Hershenberg, Rachel; Drabick, Deborah A. G.; Vivian, Dina

2013-01-01

Clinical researchers and clinical practitioners share a goal of increasing the integration of research and clinical practice, which is reflected in an evidence-based practice (EBP) approach to psychology. The EBP framework involves the integration of research findings with clinical expertise and client characteristics, values, and preferences, and consequently provides an important foundation for conducting clinically relevant research, as well as empirically based and clinically sensitive practice. Given the critical role that early training can play in the integration of science and practice and in promoting the future of the field, the present article addresses predoctoral training programs as a context for adopting an EBP approach to clinical work. We address training in the three components of EBP and provide suggestions for curriculum development and practicum training that we hope will contribute to bridging the gap between research and practice. PMID:22642520

Facial Expression Recognition Deficits and Faulty Learning: Implications for Theoretical Models and Clinical Applications

ERIC Educational Resources Information Center

Sheaffer, Beverly L.; Golden, Jeannie A.; Averett, Paige

2009-01-01

The ability to recognize facial expressions of emotion is integral in social interaction. Although the importance of facial expression recognition is reflected in increased research interest as well as in popular culture, clinicians may know little about this topic. The purpose of this article is to discuss facial expression recognition literature…

Annotation: The Similarities and Differences between Autistic Disorder and Asperger's Disorder--A Review of the Empirical Evidence

ERIC Educational Resources Information Center

Macintosh, Kathleen E.; Dissanayake, Cheryl

2004-01-01

Background: The ongoing controversy over the distinction between autistic disorder and Asperger's disorder is important to resolve because of the implications regarding an understanding of the aetiology and prognosis, and the diagnostic and clinical practices relating to these conditions. This paper provides a critical evaluation of current…

Neurodevelopmental Sequelae of Postnatal Maternal Care in Rodents: Clinical and Research Implications of Molecular Insights

ERIC Educational Resources Information Center

Kaffman, Arie; Meaney, Michael J.

2007-01-01

Parental care plays an important role in the emotional and cognitive development of the offspring. Children who have been exposed to abuse or neglect are more likely to develop numerous psychopathologies, while good parent-infant bonding is associated with improved resiliency to stress. Similar observations have also been reported in non-human…

Do Black and White Youths Differ in Levels of Psychopathic Traits? A Meta-Analysis of the Psychopathy Checklist Measures

ERIC Educational Resources Information Center

McCoy, Wendy K.; Edens, John F.

2006-01-01

Putative ethnic group differences in various forms of psychopathology may have important theoretical, clinical, and policy implications. Recently, it has been argued that individuals of African descent are more likely to be psychopathic than those of European descent (R. Lynn, 2002). Preliminary evidence from the Psychopathy Checklist: Youth…

Response Expectancy and the Placebo Effect.

PubMed

Kirsch, Irving

2018-01-01

In this chapter, I review basic tenets of response expectancy theory (Kirsch, 1985), beginning with the important distinction between response expectancies and stimulus expectancies. Although both can affect experience, the effects of response expectancies are stronger and more resistant to extinction than those of stimulus expectancies. Further, response expectancies are especially important to understanding placebo effects. The response expectancy framework is consistent with and has been amplified by the Bayesian model of predictive coding. Clinical implications of these phenomena are exemplified. © 2018 Elsevier Inc. All rights reserved.

Ethical implications for clinical practice and future research in "at risk" individuals.

PubMed

Singh, Fiza; Mirzakhanian, Heline; Fusar-Poli, Paolo; de la Fuente-Sandoval, Camilo; Cadenhead, Kristin S

2012-01-01

The last 15 years have witnessed a shift in schizophrenia research with increasing interest in earlier stages of illness with the hope of early intervention and ultimately prevention of psychotic illness. Large-scale longitudinal studies have identified clinical and biological risk factors associated with increased risk of psychotic conversion, which together with symptomatic and demographic risk factors may improve the power of prediction algorithms for psychotic transition. Despite these advances, 45-70% of at risk subjects in most samples do not convert to frank psychosis, but continue to function well below their age matched counterparts. The issue is of utmost importance in light of the upcoming DSM-V and the possible inclusion of the attenuated psychotic symptoms syndrome (APSS) diagnosis, with clinical and ethical implications. Clinical considerations include feasibility of reliably diagnosing the at risk state in non-academic medical centers, variable psychotic conversion rates, a non-uniform definition of conversion and extensive debate about treatment for individuals with an ill-defined outcome. On the ethical side, diagnosing APSS could lead to unnecessary prescribing of antipsychotics with long-term deleterious consequences, slow research by providing a false sense of comfort in the diagnosis, and have psychosocial implications for those who receive a diagnosis. Thus it may be prudent to engage at risk populations early and to use broad-spectrum treatments with low risk benefit ratios to relieve functional impairments, while simultaneously studying all subsets of the at risk population.

The Epidemiological, Morphological, and Clinical Aspects of the Cervical Ribs in Humans

PubMed Central

Spadliński, Łukasz; Cecot, Tomasz; Majos, Agata; Stefańczyk, Ludomir; Pietruszewska, Wioletta; Wysiadecki, Grzegorz; Topol, Mirosław

2016-01-01

A familiarity with the anatomy of some types of bone anomalies is necessary for clinicians involved in many medical areas. The aim of this paper is to review the newest literature concerning the morphology, embryology, clinical image, and therapeutic methods of the cervical ribs in the humans. The incidence of cervical ribs has been found to vary from 0.58% in Malaysian population to 6.2% in Turkish population. Cervical ribs have clinical implications that are generally divided into neurological or vascular. This study is of particular importance for clinicians, as early identification of cervical ribs may prevent life-threatening complications. PMID:27975060

Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan.

PubMed

Teede, H; Deeks, A; Moran, L

2010-06-30

Polycystic ovary syndrome (PCOS) is of clinical and public health importance as it is very common, affecting up to one in five women of reproductive age. It has significant and diverse clinical implications including reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, adverse cardiovascular risk profiles) and psychological features (increased anxiety, depression and worsened quality of life). Polycystic ovary syndrome is a heterogeneous condition and, as such, clinical and research agendas are broad and involve many disciplines. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental factors including lifestyle and bodyweight. Importantly, PCOS has unique interactions with the ever increasing obesity prevalence worldwide as obesity-induced insulin resistance significantly exacerbates all the features of PCOS. Furthermore, it has clinical implications across the lifespan and is relevant to related family members with an increased risk for metabolic conditions reported in first-degree relatives. Therapy should focus on both the short and long-term reproductive, metabolic and psychological features. Given the aetiological role of insulin resistance and the impact of obesity on both hyperinsulinaemia and hyperandrogenism, multidisciplinary lifestyle improvement aimed at normalising insulin resistance, improving androgen status and aiding weight management is recognised as a crucial initial treatment strategy. Modest weight loss of 5% to 10% of initial body weight has been demonstrated to improve many of the features of PCOS. Management should focus on support, education, addressing psychological factors and strongly emphasising healthy lifestyle with targeted medical therapy as required. Monitoring and management of long-term metabolic complications is also an important part of routine clinical care. Comprehensive evidence-based guidelines are needed to aid early diagnosis, appropriate investigation, regular screening and treatment of this common condition. Whilst reproductive features of PCOS are well recognised and are covered here, this review focuses primarily on the less appreciated cardiometabolic and psychological features of PCOS.

Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan

PubMed Central

2010-01-01

Polycystic ovary syndrome (PCOS) is of clinical and public health importance as it is very common, affecting up to one in five women of reproductive age. It has significant and diverse clinical implications including reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, adverse cardiovascular risk profiles) and psychological features (increased anxiety, depression and worsened quality of life). Polycystic ovary syndrome is a heterogeneous condition and, as such, clinical and research agendas are broad and involve many disciplines. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental factors including lifestyle and bodyweight. Importantly, PCOS has unique interactions with the ever increasing obesity prevalence worldwide as obesity-induced insulin resistance significantly exacerbates all the features of PCOS. Furthermore, it has clinical implications across the lifespan and is relevant to related family members with an increased risk for metabolic conditions reported in first-degree relatives. Therapy should focus on both the short and long-term reproductive, metabolic and psychological features. Given the aetiological role of insulin resistance and the impact of obesity on both hyperinsulinaemia and hyperandrogenism, multidisciplinary lifestyle improvement aimed at normalising insulin resistance, improving androgen status and aiding weight management is recognised as a crucial initial treatment strategy. Modest weight loss of 5% to 10% of initial body weight has been demonstrated to improve many of the features of PCOS. Management should focus on support, education, addressing psychological factors and strongly emphasising healthy lifestyle with targeted medical therapy as required. Monitoring and management of long-term metabolic complications is also an important part of routine clinical care. Comprehensive evidence-based guidelines are needed to aid early diagnosis, appropriate investigation, regular screening and treatment of this common condition. Whilst reproductive features of PCOS are well recognised and are covered here, this review focuses primarily on the less appreciated cardiometabolic and psychological features of PCOS. PMID:20591140

The mandible and its foramen: anatomy, anthropology, embryology and resulting clinical implications.

PubMed

Lipski, M; Tomaszewska, I M; Lipska, W; Lis, G J; Tomaszewski, K A

2013-11-01

The aim of this paper is to summarise the knowledge about the anatomy, embryology and anthropology of the mandible and the mandibular foramen and also to highlight the most important clinical implications of the current studies regarding anaesthesia performed in the region of the mandible. An electronic journal search was undertaken to identify all the relevant studies published in English. The search included MEDLINE and EMBASE databases and years from 1950 to 2012. The subject search used a combination of controlled vocabulary and free text based on the search strategy for MEDLINE using key words: 'mandible', 'mandibular', 'foramen', 'anatomy', 'embryology', 'anthropology', and 'mental'. The reference lists of all the relevant studies and existing reviews were screened for additional relevant publications. Basing on relevant manuscripts, this short review about the anatomy, embryology and anthropology of the mandible and the mandibular foramen was written.

Gender, human rights and cultural diversity: reflections on a career in transcultural psychiatry.

PubMed

Kastrup, Marianne C

2011-04-01

The three issues of gender equality, human rights and cultural diversity have dominated my organizational commitments, research, and clinical practice in transcultural psychiatry. These issues are intertwined in many ways and have broad implications for transcultural psychiatry. With increasing globalization, psychiatrists in many countries are likely to be treating patients who have migrated from different cultures and who may have been exposed to a variety of traumatic experiences that have a profound impact on their mental health. Of particular concern is the group of torture survivors and the elucidation of their symptom manifestations, as well as effective therapeutic interventions, which clearly show how human rights issues are linked to research and clinical psychiatry. The analyses of how different ethnic groups use psychiatric services, epitomize how important it is to pay attention to gender aspects in the interpretation of the findings and their therapeutic, as well as policy, implications.

The tell-tale heart: physiological reactivity during resolution of ambiguity in youth anxiety.

PubMed

Rozenman, Michelle; Vreeland, Allison; Iglesias, Marisela; Mendez, Melissa; Piacentini, John

2018-03-01

In the past decade, cognitive biases and physiological arousal have each been proposed as mechanisms through which paediatric anxiety develops and is maintained over time. Preliminary studies have found associations between anxious interpretations of ambiguity, physiological arousal, and avoidance, supporting theories that link cognition, psychophysiology, and behaviour. However, little is known about the relationship between youths' resolutions of ambiguity and physiological arousal during acute stress. Such information may have important clinical implications for use of verbal self-regulation strategies and cognitive restructuring during treatments for paediatric anxiety. In this brief report, we present findings suggesting that anxious, but not typically developing, youth select avoidant goals via non-threatening resolution of ambiguity during a stressor, and that this resolution of ambiguity is accompanied by physiological reactivity (heart rate, heart rate variability, and respiratory sinus arrhythmia). We propose future empirical research on the interplay between interpretation bias, psychophysiology, and child anxiety, as well as clinical implications.

Genetic and epigenetic regulatory mechanisms of the oxytocin receptor gene (OXTR) and the (clinical) implications for social behavior.

PubMed

Tops, Sanne; Habel, Ute; Radke, Sina

2018-03-12

Oxytocin and the oxytocin receptor (OXTR) play an important role in a large variety of social behaviors. The oxytocinergic system interacts with environmental cues and is highly dependent on interindividual factors. Deficits in this system have been linked to mental disorders associated with social impairments, such as autism spectrum disorder (ASD). This review focuses on the modulation of social behavior by alterations in two domains of the oxytocinergic system. We discuss genetic and epigenetic regulatory mechanisms and alterations in these mechanisms that were found to have clinical implications for ASD. We propose possible explanations how these alterations affect the biological pathways underlying the aberrant social behavior and point out avenues for future research. We advocate the need for integration studies that combine multiple measures covering a broad range of social behaviors and link these to genetic and epigenetic profiles. Copyright © 2018. Published by Elsevier Inc.

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.

The clinical implications of ageing for rational drug therapy.

PubMed

Shi, Shaojun; Mörike, Klaus; Klotz, Ulrich

2008-02-01

The proportion of the elderly is constantly increasing and by the year 2025 20% of the population will be above 65 years of age. With advanced age, subjects will develop multiple diseases and often need to take several drugs. This polypharmacy increases the risk for drug interactions and adverse effects. In addition, age-related physiological changes affect different biological systems and can contribute to alterations in pharmacokinetics and pharmacodynamics in older patients, which are more often seen in the frail than in the fit elderly. These features will complicate drug therapy in the elderly, and a careful dose titration is advisable. Furthermore, inappropriate drug prescription and non-adherence to medication represent common therapeutic challenges in elderly subjects. To date, there is no evidence of any effective antiageing agent. This review summarizes present knowledge of age-related problems in drug action and their clinical implications for an increasingly important population.

Target of Rapamycin (TOR) in Nutrient Signaling and Growth Control

PubMed Central

Loewith, Robbie; Hall, Michael N.

2011-01-01

TOR (Target Of Rapamycin) is a highly conserved protein kinase that is important in both fundamental and clinical biology. In fundamental biology, TOR is a nutrient-sensitive, central controller of cell growth and aging. In clinical biology, TOR is implicated in many diseases and is the target of the drug rapamycin used in three different therapeutic areas. The yeast Saccharomyces cerevisiae has played a prominent role in both the discovery of TOR and the elucidation of its function. Here we review the TOR signaling network in S. cerevisiae. PMID:22174183

Matrix metalloproteinase inhibitors as anticancer agents.

PubMed

Konstantinopoulos, Panagiotis A; Karamouzis, Michalis V; Papatsoris, Athanasios G; Papavassiliou, Athanasios G

2008-01-01

The important role of matrix metalloproteinases (MMPs) in the process of carcinogenesis is well established. However, despite very promising activity in a plethora of preclinical models, MMP inhibitors (MMPIs) failed to demonstrate a statistically significant survival advantage in advanced stage clinical trials in most human malignancies. Herein, we review the implication of MMPs in carcinogenesis, outline the pharmacology and current status of various MMPIs as anticancer agents and discuss the etiologies for the discrepancy between their preclinical and clinical evaluation. Finally, strategies for effective incorporation of MMPIs in current anticancer therapies are proposed.

Systematic Review of Bilateral Independent Periodic Discharges Written for Topical Journal Subject on Periodic Discharges.

PubMed

Freund, Brin; Kaplan, Peter W

2018-05-01

Periodic discharges (PDs) are EEG patterns that may have important clinical and prognostic implications. There are different subtypes of PDs that are delineated by their location, and each type may have different meaning regarding prognosis and clinical associations. Bilateral independent PDs are a subtype that have not been analyzed recently and remain poorly understood. In this article, we systematically review the literature to better describe bilateral independent PDs regarding underlying neuropathology, neuroimaging, and neuroexamination correlates, seizure incidence, EEG characteristics, their comparison with other PD subtypes, and prognostic meaning.

Antiplatelet Drugs

PubMed Central

Hirsh, Jack; Spencer, Frederick A.; Baglin, Trevor P.; Weitz, Jeffrey I.

2012-01-01

The article describes the mechanisms of action, pharmacokinetics, and pharmacodynamics of aspirin, dipyridamole, cilostazol, the thienopyridines, and the glycoprotein IIb/IIIa antagonists. The relationships among dose, efficacy, and safety are discussed along with a mechanistic overview of results of randomized clinical trials. The article does not provide specific management recommendations but highlights important practical aspects of antiplatelet therapy, including optimal dosing, the variable balance between benefits and risks when antiplatelet therapies are used alone or in combination with other antiplatelet drugs in different clinical settings, and the implications of persistently high platelet reactivity despite such treatment. PMID:22315278

Sex and gender differences in pain and analgesia.

PubMed

Mogil, Jeffrey S; Bailey, Andrea L

2010-01-01

It is a clinical reality that women make up the large majority of chronic pain patients, and there is now consensus from laboratory experiments that when differences are seen, women are more sensitive to pain than men. Research in this field has now begun to concentrate on finding explanations for this sex difference. Although sex differences in sociocultural, psychological, and experiential factors likely play important roles, evidence largely from animal studies has revealed surprisingly robust and often qualitative sex differences at low levels of the neuraxis. Although not yet able to affect clinical practice, the continued study of sex differences in pain may have important implications for the development of new analgesic strategies. Copyright © 2010 Elsevier B.V. All rights reserved.

[Renal oncocytoma in the single kidney after previous surgery of renal carcinoma. Apropos of 2 cases].

PubMed

Veneroni, L; Canclini, L; Berti, G L; Giola, V; Leidi, G L; Maccaroni, A; Raimoldi, A; Sironi, M; Assi, A; Bacchioni, A M

1997-12-01

Renal oncocytoma is a neoplasm which rarely occurs in patients with solitary kidney, the other being absent because of a previous nephrectomy performed for renal cancer. We present two case reports and a literature review. We have studied some important problems such as the histogenesis, the potential for malignancy, the diagnosis, the treatment and the follow up. The high incidence of coexistence of renal oncocytoma and renal cell carcinoma has important clinical implications. We would like to emphasize the importance of preoperatory FNAB, nephron sparing surgery and very careful follow up.

“There Are Too Many, but Never Enough": Qualitative Case Study Investigating Routine Coding of Clinical Information in Depression

PubMed Central

Cresswell, Kathrin; Morrison, Zoe; Sheikh, Aziz; Kalra, Dipak

2012-01-01

Background We sought to understand how clinical information relating to the management of depression is routinely coded in different clinical settings and the perspectives of and implications for different stakeholders with a view to understanding how these may be aligned. Materials and Methods Qualitative investigation exploring the views of a purposefully selected range of healthcare professionals, managers, and clinical coders spanning primary and secondary care. Results Our dataset comprised 28 semi-structured interviews, a focus group, documents relating to clinical coding standards and participant observation of clinical coding activities. We identified a range of approaches to coding clinical information including templates and order entry systems. The challenges inherent in clearly establishing a diagnosis, identifying appropriate clinical codes and possible implications of diagnoses for patients were particularly prominent in primary care. Although a range of managerial and research benefits were identified, there were no direct benefits from coded clinical data for patients or professionals. Secondary care staff emphasized the role of clinical coders in ensuring data quality, which was at odds with the policy drive to increase real-time clinical coding. Conclusions There was overall no evidence of clear-cut direct patient care benefits to inform immediate care decisions, even in primary care where data on patients with depression were more extensively coded. A number of important secondary uses were recognized by healthcare staff, but the coding of clinical data to serve these ends was often poorly aligned with clinical practice and patient-centered considerations. The current international drive to encourage clinical coding by healthcare professionals during the clinical encounter may need to be critically examined. PMID:22937106

Clinical Profiles of Children with Disruptive Behaviors Based on the Severity of Their Conduct Problems, Callous-Unemotional Traits and Emotional Difficulties.

PubMed

Andrade, Brendan F; Sorge, Geoff B; Na, Jennifer Jiwon; Wharton-Shukster, Erika

2015-08-01

This study identified clinical profiles of referred children based on the severity of callous-unemotional (CU) traits, emotional difficulties, and conduct problems. Parents of 166 children (132 males) aged 6-12 years referred to a hospital clinic because of disruptive behavior completed measures to assess these key indicators, and person-centered analysis was used to identify profiles. Four distinct profiles were identified that include: (1) Children low in severity on the three domains, (2) Children high in severity on the three domains, (3) Children high in severity in conduct problems and CU traits with minimal emotional difficulties, and (4) Children high in severity in conduct problems and emotional difficulties with minimal CU traits. Profiles differed in degree of aggression and behavioral impairment. Findings show that clinic-referred children with disruptive behaviors can be grouped based on these important indicators into profiles that have important implications for assessment and treatment selection.

Clinical implications of recent breakthroughs in amyotrophic lateral sclerosis.

PubMed

Van Damme, Philip; Robberecht, Wim

2013-10-01

This review examines the clinical implications of recent breakthroughs in amyotrophic lateral sclerosis (ALS). ALS has been found to be a highly variable condition at the clinical, genetic and mechanistic level. The study of newly discovered genetic causes for ALS has demonstrated that in addition to the effect of toxic mutant proteins, abnormalities of RNA householding contribute to motor neuron degeneration. Furthermore, the classic distinction between gain of function and loss of function may be an oversimplification of the biological reality. The most important clinical breakthrough was the finding of intronic hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) as a common cause of ALS, frontotemporal lobar degeneration (FTLD) and ALS with concomitant FTLD. This provides unambiguous evidence that ALS and FTLD represent the ends of one spectrum of neurodegenerative diseases. The high prevalence of C9orf72 mutations in patients without family history further blurs the distinction between sporadic and familial forms of ALS and FTLD. It also opens opportunities for stratified clinical trials in ALS and for the development of targeted therapies. ALS is a heterogeneous disorder that overlaps with FTLD. C9orf72 mutations are the most common cause of ALS, and add to the evidence that disturbances in RNA householding contribute to ALS.

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

Construct Validity of Fluency and Implications for the Factorial Structure of Memory

ERIC Educational Resources Information Center

Jewsbury, Paul A.; Bowden, Stephen C.

2017-01-01

Fluency is an important construct in clinical assessment and in cognitive taxonomies. In the Cattell-Horn-Carroll (CHC) model, Fluency is represented by several narrow factors that form a subset of the long-term memory encoding and retrieval (Glr) broad factor. The CHC broad classification of Fluency was evaluated in five data sets, and the CHC…

Adult Participation in Children's Word Searches: On the Use of Prompting, Hinting, and Supplying a Model

ERIC Educational Resources Information Center

Radford, Julie

2010-01-01

Although word searching in children is very common, very little is known about how adults support children in the turns following the child's search behaviours, an important topic because of the social, educational, and clinical implications. This study characterizes, in detail, teachers' use of prompting, hinting, and supplying a model. From a…

Global regulatory developments for clinical stem cell research: diversification and challenges to collaborations.

PubMed

Rosemann, Achim; Bortz, Gabriela; Vasen, Federico; Sleeboom-Faulkner, Margaret

2016-10-01

In this article, we explore regulatory developments in stem cell medicine in seven jurisdictions: Japan, China, India, Argentina, Brazil, the USA and the EU. We will show that the research methods, ethical standards and approval procedures for the market use of clinical stem cell interventions are undergoing an important process of global diversification. We will discuss the implications of this process for international harmonization and the conduct of multicountry clinical research collaborations. It will become clear that the increasing heterogeneity of research standards and regulations in the stem cell field presents a significant challenge to international clinical trial partnerships, especially with countries that diverge from the regulatory models that have been developed in the USA and the EU.

The sociocultural model of eating disorders in Mexican American women: behavioral acculturation and cognitive marginalization as moderators.

PubMed

Warren, Cortney S; Castillo, Linda G; Gleaves, David H

2010-01-01

White American cultural values of appearance are implicated in the development of body dissatisfaction. This study examined whether the relationships between awareness of White American appearance ideals, internalization of such ideals, and body dissatisfaction are moderated by behavioral acculturation and attitudinal marginalization in a sample of 94 Mexican American women. Results indicated that behavioral acculturation moderated the relationship between awareness and internalization and cognitive marginalization moderated the relationship between internalization and body dissatisfaction. Body size was positively correlated with body dissatisfaction and negatively correlated with behavioral acculturation. These findings have important implications for clinical practice and research with Mexican American women.

Intolerance of uncertainty and transdiagnostic group cognitive behavioral therapy for anxiety.

PubMed

Talkovsky, Alexander M; Norton, Peter J

2016-06-01

Recent evidence suggests intolerance of uncertainty (IU) is a transdiagnostic variable elevated across anxiety disorders. No studies have investigated IU's response to transdiagnostic group CBT for anxiety (TGCBT). This study evaluated IU outcomes following TGCBT across anxiety disorders. 151 treatment-seekers with primary diagnoses of social anxiety disorder, panic disorder, or GAD were evaluated before and after 12 weeks of TGCBT and completed self-report questionnaires at pre-, mid-, and post-treatment. IU decreased significantly following treatment. Decreases in IU predicted improvements in clinical presentation across diagnoses. IU interacted with time to predict improvement in clinical presentation irrespective of primary diagnosis. IU also interacted with time to predict improvement in clinical presentation although interactions of time with diagnosis-specific measures did not. IUS interacted with time to predict reduction in anxiety and fear symptoms, and inhibitory IU interacted with time to predicted reductions in anxiety symptoms but prospective IU did not. IU appears to be an important transdiagnostic variable in CBT implicated in both initial presentation and treatment change. Further implications are discussed. Published by Elsevier Ltd.

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.

The pursuit of certainty in diagnosing dementia: cognitive testing, childishness and stress in two British memory clinics.

PubMed

Orr, David M R

2010-12-01

By often taking as its focus the experience of illness in itself, medical anthropology has sometimes neglected the meanings that patients may assign to the diagnostic procedures that they are expected to undergo. This paper puts into anthropological perspective the author's experiences working as an assistant psychologist in two British memory clinics for the detection and treatment of dementia, using comments by patients to illustrate the significance that one aspect of these procedures--cognitive testing--had for them. These comments suggest that the meanings that patients construct with regard to such testing are complex and cannot be understood if one persists in seeing it as a neutral diagnostic tool without broader implications. It is argued that a strong association made by many patients between the cognitive tests and their childhood school experiences informs their reactions for better or worse. It is important to acknowledge the implications of this active interpretation of medical procedures if the memory clinic experience is not to become an alienating and infantilising one.

Redefining Myocardial Infarction: What Is New In The ESC/ACCF/AHA/WHF Third Universal Definition Of Myocardial Infarction?

PubMed Central

Alam, Mahboob; Virani, Salim S.; Bozkurt, Biykem

2013-01-01

Myocardial infarction (MI) is a major cause of mortality and morbidity worldwide. Each year, an estimated 785,000 persons will have a new MI in the United States alone, and approximately every minute an American will succumb to one.1 In addition, MI has major psychological and legal implications for patients and the society and is an important outcome measure in research studies. The prevalence of MI provides useful data regarding the burden of coronary artery disease and offers insight into health care planning, policy, and resource allocation. The importance of accurately and reproducibly defining MI is therefore self-evident. The Third Universal Definition of Myocardial Infarction (MI) expert consensus document was published in October 2012 by the global Myocardial Infarction Task Force.2 This landmark document was cosponsored by multiple cardiovascular societies and included both updated definitions and a modified classification of MI that have important clinical, epidemiological, and research implications. We hereby present a critical overview of this important document and summarize its key recommendations. PMID:24066201

Redefining myocardial infarction: what is new in the ESC/ACCF/AHA/WHF Third Universal Definition of myocardial infarction?

PubMed

Jneid, Hani; Alam, Mahboob; Virani, Salim S; Bozkurt, Biykem

2013-01-01

Myocardial infarction (MI) is a major cause of mortality and morbidity worldwide. Each year, an estimated 785,000 persons will have a new MI in the United States alone, and approximately every minute an American will succumb to one.1 In addition, MI has major psychological and legal implications for patients and the society and is an important outcome measure in research studies. The prevalence of MI provides useful data regarding the burden of coronary artery disease and offers insight into health care planning, policy, and resource allocation. The importance of accurately and reproducibly defining MI is therefore self-evident. The Third Universal Definition of Myocardial Infarction (MI) expert consensus document was published in October 2012 by the global Myocardial Infarction Task Force.2 This landmark document was cosponsored by multiple cardiovascular societies and included both updated definitions and a modified classification of MI that have important clinical, epidemiological, and research implications. We hereby present a critical overview of this important document and summarize its key recommendations.

ESCMID and ECMM joint guidelines on diagnosis and management of hyalohyphomycosis: Fusarium spp., Scedosporium spp. and others.

PubMed

Tortorano, A M; Richardson, M; Roilides, E; van Diepeningen, A; Caira, M; Munoz, P; Johnson, E; Meletiadis, J; Pana, Z-D; Lackner, M; Verweij, P; Freiberger, T; Cornely, O A; Arikan-Akdagli, S; Dannaoui, E; Groll, A H; Lagrou, K; Chakrabarti, A; Lanternier, F; Pagano, L; Skiada, A; Akova, M; Arendrup, M C; Boekhout, T; Chowdhary, A; Cuenca-Estrella, M; Guinea, J; Guarro, J; de Hoog, S; Hope, W; Kathuria, S; Lortholary, O; Meis, J F; Ullmann, A J; Petrikkos, G; Lass-Flörl, C

2014-04-01

Mycoses summarized in the hyalohyphomycosis group are heterogeneous, defined by the presence of hyaline (non-dematiaceous) hyphae. The number of organisms implicated in hyalohyphomycosis is increasing and the most clinically important species belong to the genera Fusarium, Scedosporium, Acremonium, Scopulariopsis, Purpureocillium and Paecilomyces. Severely immunocompromised patients are particularly vulnerable to infection, and clinical manifestations range from colonization to chronic localized lesions to acute invasive and/or disseminated diseases. Diagnosis usually requires isolation and identification of the infecting pathogen. A poor prognosis is associated with fusariosis and early therapy of localized disease is important to prevent progression to a more aggressive or disseminated infection. Therapy should include voriconazole and surgical debridement where possible or posaconazole as salvage treatment. Voriconazole represents the first-line treatment of infections due to members of the genus Scedosporium. For Acremonium spp., Scopulariopsis spp., Purpureocillium spp. and Paecilomyces spp. the optimal antifungal treatment has not been established. Management usually consists of surgery and antifungal treatment, depending on the clinical presentation. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Patients' Perceptions of Dehumanization of Patients in Dental School Settings: Implications for Clinic Management and Curriculum Planning.

PubMed

Raja, Sheela; Shah, Raveena; Hamad, Judy; Van Kanegan, Mona; Kupershmidt, Alexandra; Kruthoff, Mariela

2015-10-01

Although the importance of empathy, rapport, and anxiety/pain awareness in dentist-patient relations has been well documented, these factors continue to be an issue with patients in many dental school clinics. The aim of this study was to develop an in-depth understanding of how patients at an urban, university-affiliated medical center and its dental school's clinic experienced oral health care and to generate ideas for improving the dental school's clinical curriculum and management of the clinic. Although patient satisfaction surveys are common, in-depth patient narratives are an underutilized resource for improving dental education. In-depth qualitative interviews were conducted with 20 uninsured or underinsured dental patients at these sites, and the results were analyzed using content analysis. Major phenomena that participants discussed were the importance of empathy and good rapport with their oral health providers and provider awareness of dental pain and anxiety. Many patients also discussed feeling dehumanized during dental visits. Based on their positive and negative experiences, the participants made suggestions for how oral health professionals can successfully engage patients in treatment.

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.

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.

Micrometastases in neuroblastoma: are they clinically important?

PubMed Central

Burchill, S A

2004-01-01

Despite advances in the treatment of neuroblastoma (NBL), recurrence and metastases continue to pose major problems in clinical management. The relation between micrometastases and the development of secondary disease is not fully understood. However, accurate methods to detect low numbers of tumour cells may allow the evaluation of their role in the disease process, and by implication the possible benefits of eliminating them. Although there is substantial evidence for the increased sensitivity of current molecular methods for the detection of NBL cells compared with more conventional cytology, the clinical relevance and usefulness of detecting this disease remain controversial. The primary goal of current translational research must be to evaluate the clinical relevance of micrometastatic disease detected by these methods in multicentre prospective clinical outcome studies. Only then can the clinical usefulness of these methods be defined so that they may be introduced into relevant clinical practice. PMID:14693828

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.

Sex as a Biological Variable in Emergency Medicine Research and Clinical Practice: A Brief Narrative Review

PubMed Central

McGregor, Alyson J.; Beauchamp, Gillian A.; Wira, Charles R.; Perman, Sarah M.; Safdar, Basmah

2017-01-01

The National Institutes of Health recently highlighted the significant role of sex as a biological variable (SABV) in research design, outcome and reproducibility, mandating that this variable be accounted for in all its funded research studies. This move has resulted in a rapidly increasing body of literature on SABV with important implications for changing the clinical practice of emergency medicine (EM). Translation of this new knowledge to the bedside requires an understanding of how sex-based research will ultimately impact patient care. We use three case-based scenarios in acute myocardial infarction, acute ischemic stroke and important considerations in pharmacologic therapy administration to highlight available data on SABV in evidence-based research to provide the EM community with an important foundation for future integration of patient sex in the delivery of emergency care as gaps in research are filled. PMID:29085541

Cutaneous field cancerization: clinical, histopathological and therapeutic aspects*

PubMed Central

Torezan, Luís Antônio Ribeiro; Festa-Neto, Cyro

2013-01-01

The concept of "field cancerization" was first introduced by Slaughter in 1953 when studying the presence of histologically abnormal tissue surrounding oral squamous cell carcinoma. It was proposed to explain the development of multiple primary tumors and locally recurrent cancer. Organ systems in which field cancerization has been described since then are: head and neck (oral cavity, oropharynx, and larynx), lung, vulva, esophagus, cervix, breast, skin, colon, and bladder. Recent molecular studies support the carcinogenesis model in which the development of a field with genetically altered cells plays a central role. An important clinical implication is that fields often remain after the surgery for the primary tumor and may lead to new cancers, designated presently as "a second primary tumor" or "local recurrence," depending on the exact site and time interval. In conclusion, the development of an expanding pre-neoplastic field appears to be a critical step in epithelial carcinogenesis with important clinical consequences. Diagnosis and treatment of epithelial cancers should not only be focused on the tumor but also on the field from which it developed. The most important etiopathogenetic, clinical, histopathological and therapeutic aspects of field cancerization are reviewed in this article. PMID:24173184

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.

Clinical implications of numeracy: theory and practice.

PubMed

Nelson, Wendy; Reyna, Valerie F; Fagerlin, Angela; Lipkus, Isaac; Peters, Ellen

2008-06-01

Low numeracy is pervasive and constrains informed patient choice, reduces medication compliance, limits access to treatments, impairs risk communication, and affects medical outcomes; therefore, it is incumbent upon providers to minimize its adverse effects. We provide an overview of research on health numeracy and discuss its implications in clinical contexts. Low numeracy cannot be reliably inferred on the basis of patients' education, intelligence, or other observable characteristics. Objective and subjective assessments of numeracy are available in short forms and could be used to tailor health communication. Low scorers on these assessments are subject to cognitive biases, irrelevant cues (e.g., mood), and sharper temporal discounting. Because prevention of the leading causes of death (e.g., cancer and cardiovascular disease) depends on taking action now to prevent serious consequences later, those low in numeracy are likely to require more explanation of risk to engage in prevention behaviors. Visual displays can be used to make numerical relations more transparent, and different types of displays have different effects (e.g., greater risk avoidance). Ironically, superior quantitative processing seems to be achieved by focusing on qualitative gist and affective meaning, which has important implications for empowering patients to take advantage of the evidence in evidence-based medicine.

Acute Respiratory Distress Syndrome after Onyx Embolization of Arteriovenous Malformation

PubMed Central

Tawil, Isaac; Carlson, Andrew P.; Taylor, Christopher L.

2011-01-01

Purpose. We report a case of a 60-year-old male who underwent sequential Onyx embolizations of a cerebral arteriovenous malformation (AVM) which we implicate as the most likely etiology of subsequent acute respiratory distress syndrome (ARDS). Methods. Case report and literature review. Results. Shortly after the second Onyx embolization procedure, the patient declined from respiratory failure secondary to pulmonary edema. Clinical entities typically responsible for pulmonary edema including cardiac failure, renal failure, iatrogenic volume overload, negative-pressure pulmonary edema, and infectious etiologies were evaluated and excluded. The patient required mechanical ventilatory support for several days, delaying operative resection. The patient met clinical and radiographic criteria for ARDS. After excluding other etiologies of ARDS, we postulate that ARDS developed as a result of Onyx administration. The Onyx copolymer is dissolved in dimethyl sulfoxide (DMSO), a solvent excreted through the lungs and has been implicated in transient pulmonary side effects. Additionally, a direct toxic effect of the Onyx copolymer is postulated. Conclusion. Onyx embolization and DMSO toxicity are implicated as the etiology of ARDS given the lack of other inciting factors and the close temporal relationship. A strong physiologic rationale provides further support. Clinicians should consider this uncommon but important complication. PMID:21687580

Clinical Implications of Numeracy: Theory and Practice

PubMed Central

Reyna, Valerie F.; Fagerlin, Angela; Lipkus, Isaac; Peters, Ellen

2013-01-01

Background Low numeracy is pervasive and constrains informed patient choice, reduces medication compliance, limits access to treatments, impairs risk communication, and affects medical outcomes; therefore, it is incumbent upon providers to minimize its adverse effects. Purpose We provide an overview of research on health numeracy and discuss its implications in clinical contexts. Conclusions Low numeracy cannot be reliably inferred on the basis of patients’ education, intelligence, or other observable characteristics. Objective and subjective assessments of numeracy are available in short forms and could be used to tailor health communication. Low scorers on these assessments are subject to cognitive biases, irrelevant cues (e.g., mood), and sharper temporal discounting. Because prevention of the leading causes of death (e.g., cancer and cardiovascular disease) depends on taking action now to prevent serious consequences later, those low in numeracy are likely to require more explanation of risk to engage in prevention behaviors. Visual displays can be used to make numerical relations more transparent, and different types of displays have different effects (e.g., greater risk avoidance). Ironically, superior quantitative processing seems to be achieved by focusing on qualitative gist and affective meaning, which has important implications for empowering patients to take advantage of the evidence in evidence-based medicine. PMID:18677452

Autoinflammatory diseases in adults. Clinical characteristics and prognostic implications.

PubMed

González García, A; Patier de la Peña, J L; Ortego Centeno, N

2017-03-01

Autoinflammatory diseases are clinical conditions with inflammatory manifestations that present in a periodic or persistent manner and are caused by acquired or hereditary disorders of the innate immune response. In general, these diseases are more common in childhood, but cases have been reported in adults and are therefore important for all specialists. There are few references on these diseases in adults due to their low prevalence and underdiagnosis. The aim of this study is to review the scientific literature on these disorders to systematise their clinical, prognostic and treatment response characteristics in adults. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Interprofessional primary care in academic family medicine clinics: implications for education and training.

PubMed

Drummond, Neil; Abbott, Karen; Williamson, Tyler; Somji, Behnaz

2012-08-01

To explore the status and processes of interprofessional work environments and the implications for interprofessional education in a sample of family medicine teaching clinics. Focus group interviews using a purposive sampling procedure. Four academic family medicine clinics in Alberta. Seven family physicians, 9 registered nurses, 5 licensed practical nurses, 2 residents, 1 psychologist, 1 informatics specialist, 1 pharmacist, 1 dietitian, 1 nurse practitioner, 1 receptionist, and 1 respiratory therapist. Assessment of clinic status and performance in relation to established principles of interprofessional work and education was explored using semistructured focus group interviews. Our data supported the D'Amour and Oandasan model of successful interprofessional collaborative practice in terms of the model's main "factors" (ie, shared goals and vision, sense of belonging, governance, and the structuring of clinical care) and their constituent "elements." It is reasonable to conclude that the extent to which these factors and elements are both present and positively oriented in academic clinic settings is an important contributory factor to the establishment of interprofessional collaborative practice in primary care. Using this model, 2 of the 4 clinics were rated as expressing substantial progress in relation to interprofessional work, while the other 2 clinics were rated as less successful on that dimension. None of the clinics was identified as having a clear and explicit focus on providing interprofessional education. The key factor in relation to the implementation of interprofessional work in primary care appears to be the existence of clear and explicit leadership in that direction. Substantial scope exists for improvement in the organization, conduct, and promotion of interprofessional education for Canadian primary care.

Effects of communication with important social referents on beliefs and intentions to use condoms.

PubMed

Strader, M K; Beaman, M L; McSweeney, M

1992-06-01

Data from a 1989 survey using the condom attitude and belief instrument with 310 clients from two sexually transmitted disease clinics identified significant social referents who influence condom-use intentions. They are sexual partner, father and friends. The present study found that communication with these referents had a positive net effect on beliefs about and intentions to use condoms. Implications applicable for intervention programmes to increase condom use are to promote talking about condoms between the sexual partners and important social referents and to develop such communication skills.

Identity threat and stigma in cancer patients

PubMed Central

Marziliano, Allison; Moyer, Anne

2014-01-01

Cancer stigma has undergone an important transformation in recent decades. In general, this disease no longer fits squarely into Goffman’s classic taxonomy of stigmatized conditions. This review will demonstrate that, with important adaptations, an identity-threat model of stigma can be used to organize cancer stigma research post-Goffman. This adapted model postulates that one’s personal attributions, responses to situational threat, and disease/treatment characteristics can be used to predict identity threat and well-being of individuals with cancer. Implications for further research and clinical practice are discussed. PMID:28070343

The Hidden Complexity of Biological "Dirty Bombs": Implications for Special Operations Medical Personnel.

PubMed

Washington, Michael A; Blythe, Jauchia

The recent capture of a terrorist in Belgium carrying explosives, fecal matter, and animal tissue may indicate a shift from conventional weapons to crude bacteriological preparations as instruments of terror. It is important to note that although such weapons lack technological sophistication, bacteria are inherently complex, unpredictable, and undetectable in the field. Therefore, it is important that Special Operations medical personnel understand the complications that such seemingly simple devices can add to the treatment of casualties in the field and subsequent evaluation in the clinic. 2016.

ACADEMIC GENEALOGIES WITH RESPECT TO NARRATIVE IN HUMAN AND SOCIAL SCIENCES AND THEIR IMPLICATION FOR PUBLIC POLICIES

NASA Astrophysics Data System (ADS)

Fujii, Satoshi; Hasegawa, Taiki; Nakano, Takeshi; Hatori, Tsuyoshi

In human and society science, narrative is regarded as an important issue to understand dynamic actions of human being and society. Therefore, narrative is also expected to be important for public policies that try to improve dynamic actions of human being and society. In th is study, we review academic genealogies with respect to narratives including western philosophy, hermeneutics, historical science, historical philosophy, literary criticism, clinical psychology and sociology, narrative psychology and folklore. Then we discuss how narrative can be pragmatically applied for public policies.

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.

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.

Duration of psychotherapy has little association with outcome.

PubMed

King, Michael

2015-08-01

Does more psychotherapy deliver better outcomes? The answer to this question has important implications for patients' lives and costs to society. This issue of the BJPsych contains an analysis of data from a large clinical cohort receiving courses of talking therapy of up to 40 sessions in length. Duration of therapy was inversely correlated with outcome. Should we be surprised? © The Royal College of Psychiatrists 2015.

ADHD and Female Specific Concerns: A Review of the Literature and Clinical Implications

ERIC Educational Resources Information Center

Nussbaum, Nancy L.

2012-01-01

ADHD was once thought of as a predominantly male disorder. While this may be true for ADHD in childhood, extant research suggests that the number of women with ADHD may be nearly equal to that of men with the disorder (Faraone et al., 2000). There is accumulating research which clearly indicates subtle but important sex differences exist in the…

Medical Student Bias and Care Recommendations for an Obese versus Non-Obese Virtual Patient

PubMed Central

Persky, Susan; Eccleston, Collette P.

2010-01-01

Objective This study examined the independent effect of a patient's weight on medical students' attitudes, beliefs, and interpersonal behavior toward the patient, in addition to the clinical recommendations they make for her care. Design Seventy-six clinical-level medical students were randomly assigned to interact with a digital, virtual female patient who was visibly either obese or non-obese. Methods Interactions with the patient took place in an immersive virtual clinical environment (i.e., virtual reality) which allowed standardization of all patient behaviors and characteristics except for weight. Visual contact behavior was automatically recorded during the interaction. Afterward, participants filled out a battery of self-report questionnaires. Results Analyses revealed more negative stereotyping, less anticipated patient adherence, worse perceived health, more responsibility attributed for potentially weight-related presenting complaints, and less visual contact directed toward the obese version of a virtual patient than the non-obese version of the patient. In contrast, there was no clear evidence of bias in clinical recommendations made for the patient's care. Conclusion Biases in attitudes, beliefs, and interpersonal behavior have important implications because they can influence the tone of clinical encounters and rapport in the patient-provider relationship, which can have important downstream consequences. Gaining a clear understanding of the nature and source of weight bias in the clinical encounter is an important first step toward development of strategies to address it. PMID:20820169

Introduction: Science, Sexuality, and Psychotherapy: Shifting Paradigms.

PubMed

Cerbone, Armand R

2017-08-01

This introduction presents an overview of the current issue (73, 8) of Journal of Clinical Psychology: In Session. This issue features a series of articles, with clinical cases, each presented to illustrate the challenges faced by individuals and couples whose sexual and gender identities and expressions do not comport with traditional and cultural norms. These articles also document the challenges to the therapists who treat them. Considered individually, each article underscores the need to recognize the importance of evidence in guiding psychotherapy in cases involving sexuality. The discussions in each article offer recommendations meant to help and guide psychotherapists. Considered collectively, they raise important questions and considerations about shifting paradigms of human sexuality. Implications for assessment and treatment of cases involving sexuality and gender identity are discussed and recommended. © 2017 Wiley Periodicals, Inc.

Epilepsy, language, and social skills.

PubMed

Caplan, Rochelle

2017-10-04

Language and social skills are essential for intrapersonal and interpersonal functioning and quality of life. Since epilepsy impacts these important domains of individuals' functioning, understanding the psychosocial and biological factors involved in the relationship among epilepsy, language, and social skills has important theoretical and clinical implications. This review first describes the psychosocial and biological factors involved in the association between language and social behavior in children and in adults and their relevance for epilepsy. It reviews the findings of studies of social skills and the few studies conducted on the inter-relationship of language and social skills in pediatric and adult epilepsy. The paper concludes with suggested future research and clinical directions that will enhance early identification and treatment of epilepsy patients at risk for impaired language and social skills. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical informatics in undergraduate teaching of health informatics.

PubMed

Pantazi, Stefan V; Pantazi, Felicia; Daly, Karen

2011-01-01

We are reporting on a recent experience with Health Informatics (HI) teaching at undergraduate degree level to an audience of HI and Pharmacy students. The important insight is that effective teaching of clinical informatics must involve highly interactive, applied components in addition to the traditional theoretical material. This is in agreement with general literature underlining the importance of simulations and role playing in teaching and is well supported by our student evaluation results. However, the viability and sustainability of such approaches to teaching hinges on significant course preparation efforts. These efforts consist of time-consuming investigations of informatics technologies, applications and systems followed by the implementation of workable solutions to a wide range of technical problems. In effect, this approach to course development is an involved process that relies on a special form of applied research whose technical complexity could explain the dearth of published reports on similar approaches in HI education. Despite its difficulties, we argue that this approach can be used to set a baseline for clinical informatics training at undergraduate level and that its implications for HI education in Canada are of importance.

Medication use in pregnancy and the pregnancy and lactation labeling rule.

PubMed

Sahin, L; Nallani, S C; Tassinari, M S

2016-07-01

On 30 June 2015, the US Food and Drug Administration Pregnancy and Lactation Labeling Rule (PLLR) took effect. This rule sets new and improved standards for the inclusion of information about the use of prescription drugs and biological products during pregnancy and lactation. The new labeling requirements have important implications for clinical pharmacology as there is a subheading that is dedicated to inclusion of clinical pharmacology information that inform dosing during pregnancy and the postpartum period, if available. Published 2016. This article is a US Government work and is in the public domain in the USA.

Emotional power of music in patients with memory disorders: clinical implications of cognitive neuroscience.

PubMed

Samson, Séverine; Dellacherie, Delphine; Platel, Hervé

2009-07-01

By adapting methods of cognitive psychology to neuropsychology, we examined memory and familiarity abilities in music in relation to emotion. First we present data illustrating how the emotional content of stimuli influences memory for music. Second, we discuss recent findings obtained in patients with two different brain disorders (medically intractable epilepsy and Alzheimer's disease) that show relatively spared memory performance for music, despite severe verbal memory disorders. Studies on musical memory and its relation to emotion open up paths for new strategies in cognitive rehabilitation and reinstate the importance of examining interactions between cognitive and clinical neurosciences.

Minireview: Metabolism of Female Reproduction: Regulatory Mechanisms and Clinical Implications

PubMed Central

Babayev, Elnur; Collins, Stephen C.; Nemeth, Gabor; Horvath, Tamas L.

2014-01-01

Female fertility is highly dependent on successful regulation of energy metabolism. Central processes in the hypothalamus monitor the metabolic state of the organism and, together with metabolic hormones, drive the peripheral availability of energy for cellular functions. In the ovary, the oocyte and neighboring somatic cells of the follicle work in unison to achieve successful metabolism of carbohydrates, amino acids, and lipids. Metabolic disturbances such as anorexia nervosa, obesity, and diabetes mellitus have clinically important consequences on human reproduction. In this article, we review the metabolic determinants of female reproduction and their role in infertility. PMID:24678733

Minireview: Metabolism of female reproduction: regulatory mechanisms and clinical implications.

PubMed

Seli, Emre; Babayev, Elnur; Collins, Stephen C; Nemeth, Gabor; Horvath, Tamas L

2014-06-01

Female fertility is highly dependent on successful regulation of energy metabolism. Central processes in the hypothalamus monitor the metabolic state of the organism and, together with metabolic hormones, drive the peripheral availability of energy for cellular functions. In the ovary, the oocyte and neighboring somatic cells of the follicle work in unison to achieve successful metabolism of carbohydrates, amino acids, and lipids. Metabolic disturbances such as anorexia nervosa, obesity, and diabetes mellitus have clinically important consequences on human reproduction. In this article, we review the metabolic determinants of female reproduction and their role in infertility.

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.

Comprehensive Genomic Profiling Aids in Distinguishing Metastatic Recurrence from Second Primary Cancers

PubMed Central

Weinberg, Benjamin A.; Gowen, Kyle; Lee, Thomas K.; Ou, Sai‐Hong Ignatius; Bristow, Robert; Krill, Lauren; Almira‐Suarez, M. Isabel; Ali, Siraj M.; Miller, Vincent A.; Liu, Stephen V.

2017-01-01

Abstract Background. Metastatic recurrence after treatment for locoregional cancer is a major cause of morbidity and cancer‐specific mortality. Distinguishing metastatic recurrence from the development of a second primary cancer has important prognostic and therapeutic value and represents a difficult clinical scenario. Advances beyond histopathological comparison are needed. We sought to interrogate the ability of comprehensive genomic profiling (CGP) to aid in distinguishing between these clinical scenarios. Materials and Methods. We identified three prospective cases of recurrent tumors in patients previously treated for localized cancers in which histologic analyses suggested subsequent development of a distinct second primary. Paired samples from the original primary and recurrent tumor were subjected to hybrid capture next‐generation sequencing‐based CGP to identify base pair substitutions, insertions, deletions, copy number alterations (CNA), and chromosomal rearrangements. Genomic profiles between paired samples were compared using previously established statistical clonality assessment software to gauge relatedness beyond global CGP similarities. Results. A high degree of similarity was observed among genomic profiles from morphologically distinct primary and recurrent tumors. Genomic information suggested reclassification as recurrent metastatic disease, and patients received therapy for metastatic disease based on the molecular determination. Conclusions. Our cases demonstrate an important adjunct role for CGP technologies in separating metastatic recurrence from development of a second primary cancer. Larger series are needed to confirm our observations, but comparative CGP may be considered in patients for whom distinguishing metastatic recurrence from a second primary would alter the therapeutic approach. Implications for Practice. Distinguishing a metastatic recurrence from a second primary cancer can represent a difficult clinicopathologic problem but has important prognostic and therapeutic implications. Approaches to aid histologic analysis may improve clinician and pathologist confidence in this increasingly common clinical scenario. Our series provides early support for incorporating paired comprehensive genomic profiling in clinical situations in which determination of metastatic recurrence versus a distinct second primary cancer would influence patient management. PMID:28193735

The TallyHo polygenic mouse model of diabetes: implications in wound healing.

PubMed

Buck, Donald W; Jin, Da P; Geringer, Matthew; Hong, Seok Jong; Galiano, Robert D; Mustoe, Thomas A

2011-11-01

Impairments in wound healing represent a significant source of morbidity and mortality in patients with diabetes. To help uncover the derangements associated with diabetic wound healing, murine animal models have been extensively used. In this article, the authors present results, and the accompanying wound healing implications, from experiments across three validated wound healing models using a newer polygenic strain of diabetes. The authors investigated the wound healing impairments of the TallyHo/JnJ diabetic mouse strain, using three validated wound healing models: an incisional model, a splinted excisional model, and a cutaneous ischemia-reperfusion injury model. Appropriate control strain mice were used for comparison. Wounds were analyzed using gross, histologic, and molecular techniques. TallyHo mice displayed deficits across all three wound healing models. There was a reduced resistance/response to oxidative stress and a global decrease in the initial inflammatory response to healing. In addition, there was a global decrease in the stimulus for angiogenesis and collagen formation, ultimately leading to reduced reepithelialization, granulation tissue formation, wound contraction, and wound tensile strength. Gross and histologic findings were corroborated with molecular data, which revealed a significant down-regulation of important cytokines, including vascular endothelial growth factor, neutrophilic attractant protein-2, monocyte chemoattractant protien-1, heme oxygenase-1, interleukin-1β, and interleukin-6, when normalized to the control strain (p<0.05). The TallyHo polygenic mouse model of diabetes demonstrates predictable and clinically relevant wound healing impairments that offer important implications into the derangements of diabetic wound healing observed clinically. Therapeutics targeting these specific derangements could provide improvements in the care of diabetic wounds.

Psychopathology, trauma and delinquency: subtypes of aggression and their relevance for understanding young offenders.

PubMed

Steiner, Hans; Silverman, Melissa; Karnik, Niranjan S; Huemer, Julia; Plattner, Belinda; Clark, Christina E; Blair, James R; Haapanen, Rudy

2011-06-29

To examine the implications of an ontology of aggressive behavior which divides aggression into reactive, affective, defensive, impulsive (RADI) or "emotionally hot"; and planned, instrumental, predatory (PIP) or "emotionally cold." Recent epidemiological, criminological, clinical and neuroscience studies converge to support a connection between emotional and trauma related psychopathology and disturbances in the emotions, self-regulation and aggressive behavior which has important implications for diagnosis and treatment, especially for delinquent populations. Selective review of preclinical and clinical studies in normal, clinical and delinquent populations. In delinquent populations we observe an increase in psychopathology, and especially trauma related psychopathology which impacts emotions and self-regulation in a manner that hotly emotionally charged acts of aggression become more likely. The identification of these disturbances can be supported by findings in cognitive neuroscience. These hot aggressive acts can be delineated from planned or emotionally cold aggression. Our findings support a typology of diagnostic labels for disruptive behaviors, such as conduct disorder and oppositional defiant disorder, as it appears that these acts of hot emotional aggression are a legitimate target for psychopharmacological and other trauma specific interventions. The identification of this subtype of disruptive behavior disorders leads to more specific clinical interventions which in turn promise to improve hitherto unimpressive treatment outcomes of delinquents and patients with disruptive behavior.

[Network clusters of symptoms as elementary syndromes of psychopathology: implications for clinical practice].

PubMed

Goekoop, R; Goekoop, J G

2016-01-01

In a recent publication we reported the existence of around 11 (to 15) 'elementary syndromes' that may combine in various ways, rather like 'building blocks', to explain the wide range of psychiatric symptoms. 'Bridge symptoms' seem to be responsible both for combining large sets of symptoms into elementary syndromes and for combining the various elementary syndromes to form one globally connected network structure. To discuss the implication of these findings for clinical practice. We performed a network analysis of symptom scores. Elementary syndromes provide a massive simplification of the description of psychiatric disease. Instead of the more than 300 categories in DSM-5, we now need to consider only a handful of elementary syndromes and personality domains. This modular representation of psychiatric illnesses allows us to make a complete, systematic and efficient assessment of patients and a systematic review of treatment options. Clinicians, patients, managerial staff and insurance companies can verify whether symptom reduction is taking place in the most important domains of psychopathology. Unlike classic multidimensional methods of disease description, network models of psychopathology can be used to explain comorbidity patterns, predict the clinical course of psychopathology and to designate primary targets for therapeutic interventions. A network view on psychopathology could significantly improve everyday clinical practice.

New insight in expression, transport, and secretion of brain-derived neurotrophic factor: Implications in brain-related diseases

PubMed Central

Adachi, Naoki; Numakawa, Tadahiro; Richards, Misty; Nakajima, Shingo; Kunugi, Hiroshi

2014-01-01

Brain-derived neurotrophic factor (BDNF) attracts increasing attention from both research and clinical fields because of its important functions in the central nervous system. An adequate amount of BDNF is critical to develop and maintain normal neuronal circuits in the brain. Given that loss of BDNF function has been reported in the brains of patients with neurodegenerative or psychiatric diseases, understanding basic properties of BDNF and associated intracellular processes is imperative. In this review, we revisit the gene structure, transcription, translation, transport and secretion mechanisms of BDNF. We also introduce implications of BDNF in several brain-related diseases including Alzheimer’s disease, Huntington’s disease, depression and schizophrenia. PMID:25426265

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

The clinical educator and complexity: a review.

PubMed

Schoo, Adrian; Kumar, Koshila

2018-02-08

Complexity science perspectives have helped in examining fundamental assumptions about learning and teaching in the health professions. The implications of complexity thinking for how we understand the role and development of the clinical educator is less well articulated. This review article outlines: the key principles of complexity science; a conceptual model that situates the clinical educator in a complex system; and the implications for the individual, organisation and the system. Our conceptual model situates the clinical educator at the centre of a complex and dynamic system spanning four domains and multiple levels. The four domains are: personal (encompassing personal/professional needs and expectations); health services (health agencies and their consumers); educational (educational institutions and their health students); and societal (local community/region and government). The system also comprises: micro or individual, meso or organisational, and macro or socio-political levels. Our model highlights that clinical educators are situated within a complex system comprising different agents and connections. It emphasises that individuals, teams and organisations need to recognise and be responsive to the unpredictability, interconnectedness and evolving nature of this system. Importantly, our article also calls for an epistemological shift from faculty development to capacity building in health professions education, aimed at developing individual, team, organisational and system capabilities to work with(in) complexity. Clinical educators are situated within a complex system comprising different agents and connections. © 2018 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Feed-forward transcriptional programming by nuclear receptors: regulatory principles and therapeutic implications.

PubMed

Sasse, Sarah K; Gerber, Anthony N

2015-01-01

Nuclear receptors (NRs) are widely targeted to treat a range of human diseases. Feed-forward loops are an ancient mechanism through which single cell organisms organize transcriptional programming and modulate gene expression dynamics, but they have not been systematically studied as a regulatory paradigm for NR-mediated transcriptional responses. Here, we provide an overview of the basic properties of feed-forward loops as predicted by mathematical models and validated experimentally in single cell organisms. We review existing evidence implicating feed-forward loops as important in controlling clinically relevant transcriptional responses to estrogens, progestins, and glucocorticoids, among other NR ligands. We propose that feed-forward transcriptional circuits are a major mechanism through which NRs integrate signals, exert temporal control over gene regulation, and compartmentalize client transcriptomes into discrete subunits. Implications for the design and function of novel selective NR ligands are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

Serotonin System Implication in l-DOPA-Induced Dyskinesia: From Animal Models to Clinical Investigations

PubMed Central

Carta, Manolo; Tronci, Elisabetta

2014-01-01

In the recent years, the serotonin system has emerged as a key player in the induction of l-DOPA-induced dyskinesia (LID) in animal models of Parkinson’s disease. In fact, serotonin neurons possess the enzymatic machinery able to convert exogenous l-DOPA to dopamine (DA), and mediate its vesicular storage and release. However, serotonin neurons lack a feedback control mechanism able to regulate synaptic DA levels. While in a situation of partial DA depletion spared DA terminals can buffer DA released from serotonin neurons, the progression of DA neuron degeneration impairs this protective mechanism, causing swings in synaptic DA levels and pulsatile stimulation of post-synaptic DA receptors. In line with this view, removal of serotonin neurons by selective toxin, or pharmacological silencing of their activity, produced complete suppression of LID in animal models of Parkinson’s disease. In this article, we will revise the experimental evidence pointing to the important role of serotonin neurons in dyskinesia, and we will discuss the clinical implications. PMID:24904522

Hypertensive response to exercise: mechanisms and clinical implication.

PubMed

Kim, Darae; Ha, Jong-Won

2016-01-01

A hypertensive response to exercise (HRE) is frequently observed in individuals without hypertension or other cardiovascular disease. However, mechanisms and clinical implication of HRE is not fully elucidated. Endothelial dysfunction and increased stiffness of large artery contribute to development of HRE. From neurohormonal aspects, excess stimulation of sympathetic nervous system and augmented rise of angiotensin II seems to be important mechanism in HRE. Increasing evidences indicates that a HRE is associated with functional and structural abnormalities of left ventricle, especially when accompanied by increased central blood pressure. A HRE harbors prognostic significance in future development of hypertension and increased cardiovascular events, particularly if a HRE is documented in moderate intensity of exercise. As supported by previous studies, a HRE is not a benign phenomenon, however, currently, whether to treat a HRE is controversial with uncertain treatment strategy. Considering underlying mechanisms, angiotensin receptor blockers and beta blockers can be suggested in individuals with HRE, however, evidences for efficacy and outcomes of treatment of HRE in individuals without hypertension is scarce and therefore warrants further studies.

Stress among mothers of children with intellectual disabilities in urban India: role of gender and maternal coping.

PubMed

John, Aesha

2012-07-01

The study assessed stress among mothers of young children with intellectual disabilities in urban India and examined the extent to which child functioning and maternal coping predict maternal stress. Through qualitative analyses, the study identified negative and positive dimensions of Indian mothers' caregiving experiences. Mothers completed Parenting Stress Index-Short Form, and children's teachers completed Vineland-II teacher rating form. Maternal responses to a semi-structured interview were rated to assess maternal coping and content analysed to derive qualitative themes. Three-fourths of the sample obtained a clinically significant stress score, and maternal coping emerged as a robust predictor of stress for mothers of boys with intellectual disabilities. Qualitative analyses indicated positive and negative maternal experiences related to self, child, family and community. The high level of stress has important clinical implications. Similarly, the significant role of maternal coping, moderating role of child gender and the multidimensional caregiving experiences have implications for future research and family interventions in India. © 2012 Blackwell Publishing Ltd.

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

The neurophysiology of pain perception and hypnotic analgesia: implications for clinical practice.

PubMed

Jensen, Mark P

2008-10-01

Although there remains much to be learned, a great deal is now known about the neurophysiological processes involved in the experience of pain. Research confirms that there is no single focal "center" in the brain responsible for the experience of pain. Rather, pain is the end product of a number of integrated networks that involve activity at multiple cortical and subcortical sites. Our current knowledge about the neurophysiological mechanisms of pain has important implications for understanding the mechanisms underlying the effects of hypnotic analgesia treatments, as well as for improving clinical practice. This article is written for the clinician who uses hypnotic interventions for pain management. It begins with an overview of what is known about the neurophysiological basis of pain and hypnotic analgesia, and then discusses how clinicians can use this knowledge for (1) organizing the types of suggestions that can be used when providing hypnotic treatment, and (2) maximizing the efficacy of hypnotic interventions in clients presenting with pain problems.

The kidney and type 2 diabetes mellitus: therapeutic implications of SGLT2 inhibitors.

PubMed

Weir, Matthew R

2016-01-01

Understanding the role of the kidneys in type 2 diabetes mellitus (T2DM) has taken on an increased importance in recent years with the arrival of sodium-glucose co-transporter 2 (SGLT2) inhibitors - antihyperglycemic agents (AHAs) that specifically target the kidneys. This review includes an update on the physiology of the kidneys, their role in the pathophysiology of T2DM, and the mechanisms implicated in the development and progression of diabetic kidney disease, such as glomerular hyperfiltration and inflammation. It also discusses renal issues that could influence the choice of AHA for patients with T2DM, including special populations such as patients with concomitant chronic kidney disease. The most recent data published on the clinical efficacy and safety of the SGLT2 inhibitors canagliflozin, dapagliflozin, and empagliflozin and their effects on renal function are presented, showing how the renally mediated mechanisms of action of these agents translate into clinical benefits, including the potential for renoprotection. The observed positive effects of these agents on measures such as glucose control, estimated glomerular filtration rate, albumin-to-creatinine ratio, blood pressure, and body weight in patients both with and without impaired renal function suggest that SGLT2 inhibitors represent an important extension to the diabetes treatment armamentarium.

BMI-1 Promotes Self-Renewal of Radio- and Temozolomide (TMZ)-Resistant Breast Cancer Cells.

PubMed

Yan, Yanfang; Wang, Ying; Zhao, Pengxin; Ma, Weiyuan; Hu, Zhigang; Zhang, Kaili

2017-12-01

Breast cancer is a hormone-dependent malignancy and is the most prevalent cause of cancer-related mortality among females. Radiation therapy and chemotherapy are common treatments of breast cancer. However, tumor relapse and metastasis following therapy are major clinical challenges. The importance of B-lymphoma Moloney murine leukemia virus insertion region-1 (BMI-1) was implicated in cell proliferation, stem cell maintenance, and tumor initiation. We established radio- and temozolomide (TMZ)-resistant (IRC-R) MCF-7 and MDA-MB-231 cell lines to investigate the mechanism involved in therapeutic resistance. Cell proliferation and sphere number were dramatically elevated, and BMI-1 was remarkably upregulated, in IRC-R cells compared to parental cells. Silencing BMI-1 by RNA interference only affected the cell proliferation of IRC-R but not parental cells, suggesting the critical role of BMI-1 in radio- and TMZ resistance. We used a xenograft mice model to elucidate that BMI-1 was necessary in tumor development by assessing tumor volume and Ki67 expression. We found that Hedgehog (Hhg) signaling exerted synergized functions together with BMI-1, implicating the importance of BMI-1 in Hhg signaling. Downregulation of BMI-1 could be an effective strategy to suppress tumor growth, which supports the potential clinical use of targeting BMI-1 in breast cancer treatment.

Demographic variables, clinical aspects, and medicolegal implications in a population of patients with adjustment disorder.

PubMed

Anastasia, Annalisa; Colletti, Chiara; Cuoco, Valentina; Quartini, Adele; Urso, Stefania; Rinaldi, Raffaella; Bersani, Giuseppe

2016-01-01

Although adjustment disorder (AD) is considered as residual diagnosis and receives little attention in research, it plays an important role in clinical practice and also assumes an increasingly important role in the field of legal medicine, where the majority of diagnostic frameworks (eg, mobbing) often refer to AD. Our study aimed to look for specific stressor differences among demographic and clinical variables in a naturalistic setting of patients with AD. A restrospective statistical analysis of the data of patients diagnosed with AD from November 2009 to September 2012, identified via manual search from the archive of the outpatient setting at the University Unit of Psychiatry "A. Fiorini" Hospital, Terracina (Latina, Italy), was performed. The sample consisted of 93 patients (46 males and 47 females), aged between 26 and 85, with medium-high educational level who were mainly employed. In most cases (54.80%), a diagnosis of AD with mixed anxiety and depressed mood was made. In all, 72% of the sample reported a negative family history for psychiatric disorders. In 22.60%, a previous history of psychopathology, especially mood disorders (76.19%), was reported. The main stressors linked to the development of AD were represented by working problems (32.30%), family problems (23.70%), and/or somatic disease (22.60%) with significant differences with respect to age and sex. Half of the patients were subjected to a single first examination; 24.47% requested a copy of medical records. Confirming previous data from previous reports, our results suggest that AD may have a distinct profile in demographic and clinical terms. Increased scientific attention is hoped, particularly focused on addressing a better definition of diagnostic criteria, whose correctness and accuracy are critical, especially in situations with medicolegal implications.

Demographic variables, clinical aspects, and medicolegal implications in a population of patients with adjustment disorder

PubMed Central

Anastasia, Annalisa; Colletti, Chiara; Cuoco, Valentina; Quartini, Adele; Urso, Stefania; Rinaldi, Raffaella; Bersani, Giuseppe

2016-01-01

Introduction Although adjustment disorder (AD) is considered as residual diagnosis and receives little attention in research, it plays an important role in clinical practice and also assumes an increasingly important role in the field of legal medicine, where the majority of diagnostic frameworks (eg, mobbing) often refer to AD. Our study aimed to look for specific stressor differences among demographic and clinical variables in a naturalistic setting of patients with AD. Methods A restrospective statistical analysis of the data of patients diagnosed with AD from November 2009 to September 2012, identified via manual search from the archive of the outpatient setting at the University Unit of Psychiatry “A. Fiorini” Hospital, Terracina (Latina, Italy), was performed. Results The sample consisted of 93 patients (46 males and 47 females), aged between 26 and 85, with medium–high educational level who were mainly employed. In most cases (54.80%), a diagnosis of AD with mixed anxiety and depressed mood was made. In all, 72% of the sample reported a negative family history for psychiatric disorders. In 22.60%, a previous history of psychopathology, especially mood disorders (76.19%), was reported. The main stressors linked to the development of AD were represented by working problems (32.30%), family problems (23.70%), and/or somatic disease (22.60%) with significant differences with respect to age and sex. Half of the patients were subjected to a single first examination; 24.47% requested a copy of medical records. Conclusion Confirming previous data from previous reports, our results suggest that AD may have a distinct profile in demographic and clinical terms. Increased scientific attention is hoped, particularly focused on addressing a better definition of diagnostic criteria, whose correctness and accuracy are critical, especially in situations with medicolegal implications. PMID:27099504

A review of the clinical implications of bisphosphonates in dentistry.

PubMed

Borromeo, G L; Tsao, C E; Darby, I B; Ebeling, P R

2011-03-01

Bisphosphonates are drugs that suppress bone turnover and are commonly prescribed to prevent skeletal related events in malignancy and for benign bone diseases such as osteoporosis. Bisphosphonate associated jaw osteonecrosis (ONJ) is a potentially debilitating, yet poorly understood condition. A literature review was undertaken to review the dental clinical implications of bisphosphonates. The present paper briefly describes the postulated pathophysiology of ONJ and conditions with similar clinical presentations. The implications of bisphosphonates for implantology, periodontology, orthodontics and endodontics are reviewed. Whilst bisphosphonates have potential positive applications in some clinical settings, periodontology particularly, further clinical research is limited by the risk of ONJ. Prevention and management are reviewed, including guidelines for reducing cumulative intravenous bisphosphonate dose, cessation of bisphosphonates prior to invasive dental treatment or after ONJ development, and the use of serum beta-CTX-1 in assessing risk. In the context of substantial uncertainty, the implications of bisphosphonate use in the dental clinical setting are still being determined. © 2010 Australian Dental Association.

Precursor Lesions of Urologic Malignancies.

PubMed

Khani, Francesca; Robinson, Brian D

2017-12-01

- Precursor lesions of urologic malignancies are established histopathologic entities, which are important not only to recognize for clinical purposes, but also to further investigate at the molecular level in order to gain a better understanding of the pathogenesis of these malignancies. - To provide a brief overview of precursor lesions to the most common malignancies that develop within the genitourinary tract with a focus on their clinical implications, histologic features, and molecular characteristics. - Literature review from PubMed, urologic pathology textbooks, and the 4th edition of the World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs. All photomicrographs were taken from cases seen at Weill Cornell Medicine or from the authors' personal slide collections. - The clinical importance and histologic criteria are well established for the known precursor lesions of the most common malignancies throughout the genitourinary tract, but further investigation is warranted at the molecular level to better understand the pathogenesis of these lesions. Such investigation may lead to better risk stratification of patients and potentially novel treatments.

A practical review of prognostic correlations of molecular biomarkers in glioblastoma.

PubMed

Karsy, Michael; Neil, Jayson A; Guan, Jian; Mahan, Mark A; Mark, Mahan A; Colman, Howard; Jensen, Randy L

2015-03-01

Despite extensive efforts in research and therapeutics, achieving longer survival for patients with glioblastoma (GBM) remains a formidable challenge. Furthermore, because of rapid advances in the scientific understanding of GBM, communication with patients regarding the explanations and implications of genetic and molecular markers can be difficult. Understanding the important biomarkers that play a role in GBM pathogenesis may also help clinicians in educating patients about prognosis, potential clinical trials, and monitoring response to treatments. This article aims to provide an up-to-date review that can be discussed with patients regarding common molecular markers, namely O-6-methylguanine-DNA methyltransferase (MGMT), isocitrate dehydrogenase 1 and 2 (IDH1/2), p53, epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K), and 1p/19q. The importance of the distinction between a prognostic and a predictive biomarker as well as clinical trials regarding these markers and their relevance to clinical practice are discussed.

Current insights into the genetic basis of diabetes mellitus in children and adolescents.

PubMed

Rubio-Cabezas, Oscar; Argente, Jesús

2008-10-01

Diabetes mellitus (DM) is one of the most common chronic diseases in children and adolescents, and type 1 DM accounts for more than 95% of cases. Nevertheless, over the last years it has become apparent that not all cases of DM presenting in children have an autoimmune basis. In addition to type 2 DM, which continues to be an infrequent diagnosis among pediatric patients in most countries worldwide, several forms of monogenic DM may present during childhood and are responsible for the disease in 1-3% of patients. In these disorders, DM is usually associated with either specific clinical syndromes or a characteristic age of onset. Molecular diagnosis, increasingly available, improves both clinical management and quality of life, and is also important for genetic counselling. This review aims to provide physicians taking care of children with DM with some important clues in order to make an accurate diagnosis in these patients and understand its implication in clinical management.

Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy.

PubMed

Ferretti, Francesca; Gisslen, Magnus; Cinque, Paola; Price, Richard W

2015-06-01

CNS infection is a nearly constant facet of systemic CNS infection and is generally well controlled by suppressive systemic antiretroviral therapy (ART). However, there are instances when HIV can be detected in the cerebrospinal fluid (CSF) despite suppression of plasma viruses below the clinical limits of measurement. We review three types of CSF viral escape: asymptomatic, neuro-symptomatic, and secondary. The first, asymptomatic CSF escape, is seemingly benign and characterized by lack of discernable neurological deterioration or subsequent CNS disease progression. Neuro-symptomatic CSF escape is an uncommon, but important, entity characterized by new or progressive CNS disease that is critical to recognize clinically because of its management implications. Finally, secondary CSF escape, which may be even more uncommon, is defined by an increase of CSF HIV replication in association with a concomitant non-HIV infection, as a consequence of the local inflammatory response. Understanding these CSF escape settings not only is important for clinical diagnosis and management but also may provide insight into the CNS HIV reservoir.

Clinical Significance and Characteristic Clinical Differences of Cytolytic Vaginosis in Recurrent Vulvovaginitis.

PubMed

Yang, Shuhua; Zhang, Yuexiang; Liu, Ying; Wang, Jianhong; Chen, Shuqin; Li, Shuxia

2017-01-01

The study aimed to evaluate whether cytolytic vaginosis (CV) has important clinical implications for recurrent vulvovaginitis and to identify clinical differences between CV and vulvovaginal candidosis (VVC). Medical histories, physical examinations and laboratory findings were used to diagnose and assess the prevalence rates of various vulvovaginal infections among 536 women with recurrent vulvovaginitis. Chi-square and Fisher exact tests were used to compare age, menstrual cycle phase at episode onset, symptoms/signs of infection and discharge characteristics between CV and VVC with single infection. Among the 484 women with a single-infection recurrent vulvovaginitis, the prevalence of CV (n = 143; 26.7%) was second only to VVC (n = 196; 36.6%). CV symptoms occurred predominantly during the ovulatory and luteal phases. Meanwhile, VVC episodes were not concentrated premenstrually, but rather occurred throughout the menstrual cycle. Significant differences were found in the vaginal pH, discharge characteristics and frequency of inflammatory symptoms between the 2 groups. CV is clinically important, because it is a common cause of recurrent vulvovaginitis. To distinguish CV from VVC, gynecologists should consider the patient's medical history, physical and laboratory findings, vaginal pH and vaginal discharge characteristics. © 2016 S. Karger AG, Basel.

Transcranial magnetic stimulation as an investigative tool for motor dysfunction and recovery in stroke: an overview for neurorehabilitation clinicians

PubMed Central

Cortes, Mar; Black-Schaffer, Randie M; Edwards, Dylan J

2012-01-01

Rationale An improved understanding of motor dysfunction and recovery after stroke has important clinical implications that may lead to the design of more effective rehabilitation strategies for patients with hemiparesis. Scope Transcranial magnetic stimulation (TMS) is a safe and painless tool that has been used in conjunction with other existing diagnostic tools to investigate motor pathophysiology in stroke patients. Since TMS emerged over two decades ago, its application in clinical and basic neuroscience has expanded worldwide. TMS can quantify the corticomotor excitability properties of clinically affected and unaffected muscles, and probe local cortical networks, as well as remote but functionally related areas. This provides novel insight into the physiology of neural circuits underlying motor dysfunction, and brain reorganization during the motor recovery process. This important tool needs to be used with caution by clinical investigators, its limitations need to be understood and the results should be interpreted along with clinical evaluation in this patient population. Summary In this review, we provide an overview of the rationale, implementation and limitations of TMS to study stroke motor physiology. This knowledge may be useful to guide future rehabilitation treatments by assessing and promoting functional plasticity. PMID:22624621

Genomewide search and genetic localization of a second gene associated with autosomal dominant branchio-oto-renal syndrome: clinical and genetic implications.

PubMed Central

Kumar, S; Deffenbacher, K; Marres, H A; Cremers, C W; Kimberling, W J

2000-01-01

Branchio-oto-renal (BOR) syndrome is characterized by ear malformations, cervical fistulas, hearing loss, and renal anomalies. It is an autosomal dominant disorder with variable clinical manifestations. The most common features of BOR syndrome are branchial, hearing, and renal anomalies. However, many affected subjects have been observed with branchial-cleft anomalies and hearing loss but without renal anomalies, a condition called "branchio-otic" (BO) syndrome. It is logical to question whether the BOR and BO syndromes are allelic or whether they represent distinct genetic entities. We identified a very large extended family whose members had branchial and hearing anomalies associated with commissural lip pits that segregated in an autosomal dominant fashion. Using a genomewide search strategy, we identified genetic linkage, with a maximum LOD score of 4.81 at recombination fraction 0, between the BO phenotype and polymorphic marker D1S2757 in the genetic region of chromosome 1q31. This is the first report of linkage for a second gene associated with BOR syndrome. The findings have important clinical implications and will provide insight into the genetic basis of BOR syndrome. PMID:10762556

Advances in the molecular genetics of gliomas - implications for classification and therapy.

PubMed

Reifenberger, Guido; Wirsching, Hans-Georg; Knobbe-Thomsen, Christiane B; Weller, Michael

2017-07-01

Genome-wide molecular-profiling studies have revealed the characteristic genetic alterations and epigenetic profiles associated with different types of gliomas. These molecular characteristics can be used to refine glioma classification, to improve prediction of patient outcomes, and to guide individualized treatment. Thus, the WHO Classification of Tumours of the Central Nervous System was revised in 2016 to incorporate molecular biomarkers - together with classic histological features - in an integrated diagnosis, in order to define distinct glioma entities as precisely as possible. This paradigm shift is markedly changing how glioma is diagnosed, and has important implications for future clinical trials and patient management in daily practice. Herein, we highlight the developments in our understanding of the molecular genetics of gliomas, and review the current landscape of clinically relevant molecular biomarkers for use in classification of the disease subtypes. Novel approaches to the genetic characterization of gliomas based on large-scale DNA-methylation profiling and next-generation sequencing are also discussed. In addition, we illustrate how advances in the molecular genetics of gliomas can promote the development and clinical translation of novel pathogenesis-based therapeutic approaches, thereby paving the way towards precision medicine in neuro-oncology.

Atherosclerosis in epilepsy: its causes and implications.

PubMed

Hamed, Sherifa A

2014-12-01

Evidence from epidemiological, longitudinal, prospective, double-blinded clinical trials as well as case reports documents age-accelerated atherosclerosis with increased carotid artery intima media thickness (CA-IMT) in patients with epilepsy. These findings raise concern regarding their implications for age-accelerated cognitive and behavioral changes in midlife and risk of later age-related cognitive disorders including neurodegenerative processes such as Alzheimer's disease (AD). Chronic epilepsy, cerebral atherosclerosis, and age-related cognitive disorders including AD share many clinical manifestations (e.g. characteristic cognitive deficits), risk factors, and structural and pathological brain abnormalities. These shared risk factors include increased CA-IMT, hyperhomocysteinemia (HHcy), lipid abnormalities, weight gain and obesity, insulin resistance (IR), and high levels of inflammatory and oxidative stresses. The resulting brain structural and pathological abnormalities include decreased volume of the hippocampus, increased cortical thinning of the frontal lobe, ventricular expansion and increased white matter ischemic disease, total brain atrophy, and β-amyloid protein deposition in the brain. The knowledge that age-accelerated atherosclerosis may contribute to age-accelerated cognitive and behavioral abnormalities and structural brain pathologies in patients with chronic epilepsy represents an important research path to pursue future clinical and management considerations. Copyright © 2014 Elsevier Inc. All rights reserved.

BET inhibitors in metastatic prostate cancer: therapeutic implications and rational drug combinations.

PubMed

Markowski, Mark C; De Marzo, Angelo M; Antonarakis, Emmanuel S

2017-12-01

The bromodomain and extra-terminal (BET) family of proteins are epigenetic readers of acetylated histones regulating a vast network of protein expression across many different cancers. Therapeutic targeting of BET is an attractive area of clinical development for metastatic castration-resistant prostate cancer (mCRPC), particularly due to its putative effect on c-MYC expression and its interaction with the androgen receptor (AR). Areas covered: We speculate that a combination approach using inhibitors of BET proteins (BETi) with other targeted therapies may be required to improve the therapeutic index of BET inhibition in the management of prostate cancer. Preclinical data has identified several molecular targets that may enhance the effect of BET inhibition in the clinic. This review will summarize the known preclinical data implicating BET as an important therapeutic target in advanced prostate cancer, highlight the ongoing clinical trials targeting this protein family, and speculate on rationale combination strategies using BETi together with other agents in prostate cancer. A literature search using Pubmed was performed for this review. Expert opinion: Use of BETi in the treatment of mCRPC patients may require the addition of a second novel agent.

Advancing understanding of executive function impairments and psychopathology: bridging the gap between clinical and cognitive approaches

PubMed Central

Snyder, Hannah R.; Miyake, Akira; Hankin, Benjamin L.

2015-01-01

Executive function (EF) is essential for successfully navigating nearly all of our daily activities. Of critical importance for clinical psychological science, EF impairments are associated with most forms of psychopathology. However, despite the proliferation of research on EF in clinical populations, with notable exceptions clinical and cognitive approaches to EF have remained largely independent, leading to failures to apply theoretical and methodological advances in one field to the other field and hindering progress. First, we review the current state of knowledge of EF impairments associated with psychopathology and limitations to the previous research in light of recent advances in understanding and measuring EF. Next, we offer concrete suggestions for improving EF assessment. Last, we suggest future directions, including integrating modern models of EF with state of the art, hierarchical models of dimensional psychopathology as well as translational implications of EF-informed research on clinical science. PMID:25859234

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.

Predicting performance: relative importance of students' background and past performance.

PubMed

Stegers-Jager, Karen M; Themmen, Axel P N; Cohen-Schotanus, Janke; Steyerberg, Ewout W

2015-09-01

Despite evidence for the predictive value of both pre-admission characteristics and past performance at medical school, their relative contribution to predicting medical school performance has not been thoroughly investigated. This study was designed to determine the relative importance of pre-admission characteristics and past performance in medical school in predicting student performance in pre-clinical and clinical training. This longitudinal prospective study followed six cohorts of students admitted to a Dutch, 6-year, undergraduate medical course during 2002-2007 (n = 2357). Four prediction models were developed using multivariate logistic regression analysis. Main outcome measures were 'Year 1 course completion within 1 year' (models 1a, 1b), 'Pre-clinical course completion within 4 years' (model 2) and 'Achievement of at least three of five clerkship grades of ≥ 8.0' (model 3). Pre-admission characteristics (models 1a, 1b, 2, 3) and past performance at medical school (models 1b, 2, 3) were included as predictor variables. In model 1a - including pre-admission characteristics only - the strongest predictor for Year 1 course completion was pre-university grade point average (GPA). Success factors were 'selected by admission testing' and 'age > 21 years'; risk factors were 'Surinamese/Antillean background', 'foreign pre-university degree', 'doctor parent' and male gender. In model 1b, number of attempts and GPA at 4 months were the strongest predictors for Year 1 course completion, and male gender remained a risk factor. Year 1 GPA was the strongest predictor for pre-clinical course completion, whereas being male or aged 19-21 years were risk factors. Pre-clinical course GPA positively predicted clinical performance, whereas being non-Dutch or a first-generation university student were important risk factors for lower clinical grades. Nagelkerke's R(2) ranged from 0.16 to 0.62. This study not only confirms the importance of past performance as a predictor of future performance in pre-clinical training, but also reveals the importance of a student's background as a predictor in clinical training. These findings have important practical implications for selection and support during medical school. © 2015 John Wiley & Sons Ltd.

[HIV infection: future perspective for a so-called fatal disease?].

PubMed

von Overbeck, J; Iten, A

1997-03-29

During the last 18 months, our knowledge and possibilities in the field of HIV infections have progressed in four principal domains: (1) better understanding of the dynamics of HIV infections and in particular of the importance of viral replication during the phase of latency, (2) possibility of measuring the viral charge and its use for diagnosis and to follow treatment, (3) access to very effective new anti-retroviral substances which permit hope of long-term stabilization of the infection, (4) clinical demonstration that combined treatments are superior to monotherapy. While, at the beginning of 1996, only three medications were commercialized, there were eight at the end of that year. This paper describes the implications for daily practice of recent scientific discoveries in the field of HIV infection. The importance of compliance is discussed, as well as that of clinical research.

Aspergillus Section Fumigati Typing by PCR-Restriction Fragment Polymorphism▿

PubMed Central

Staab, Janet F.; Balajee, S. Arunmozhi; Marr, Kieren A.

2009-01-01

Recent studies have shown that there are multiple clinically important members of the Aspergillus section Fumigati that are difficult to distinguish on the basis of morphological features (e.g., Aspergillus fumigatus, A. lentulus, and Neosartorya udagawae). Identification of these organisms may be clinically important, as some species vary in their susceptibilities to antifungal agents. In a prior study, we utilized multilocus sequence typing to describe A. lentulus as a species distinct from A. fumigatus. The sequence data show that the gene encoding β-tubulin, benA, has high interspecies variability at intronic regions but is conserved among isolates of the same species. These data were used to develop a PCR-restriction fragment length polymorphism (PCR-RFLP) method that rapidly and accurately distinguishes A. fumigatus, A. lentulus, and N. udagawae, three major species within the section Fumigati that have previously been implicated in disease. Digestion of the benA amplicon with BccI generated unique banding patterns; the results were validated by screening a collection of clinical strains and by in silico analysis of the benA sequences of Aspergillus spp. deposited in the GenBank database. PCR-RFLP of benA is a simple method for the identification of clinically important, similar morphotypes of Aspergillus spp. within the section Fumigati. PMID:19403766

Aspergillus section Fumigati typing by PCR-restriction fragment polymorphism.

PubMed

Staab, Janet F; Balajee, S Arunmozhi; Marr, Kieren A

2009-07-01

Recent studies have shown that there are multiple clinically important members of the Aspergillus section Fumigati that are difficult to distinguish on the basis of morphological features (e.g., Aspergillus fumigatus, A. lentulus, and Neosartorya udagawae). Identification of these organisms may be clinically important, as some species vary in their susceptibilities to antifungal agents. In a prior study, we utilized multilocus sequence typing to describe A. lentulus as a species distinct from A. fumigatus. The sequence data show that the gene encoding beta-tubulin, benA, has high interspecies variability at intronic regions but is conserved among isolates of the same species. These data were used to develop a PCR-restriction fragment length polymorphism (PCR-RFLP) method that rapidly and accurately distinguishes A. fumigatus, A. lentulus, and N. udagawae, three major species within the section Fumigati that have previously been implicated in disease. Digestion of the benA amplicon with BccI generated unique banding patterns; the results were validated by screening a collection of clinical strains and by in silico analysis of the benA sequences of Aspergillus spp. deposited in the GenBank database. PCR-RFLP of benA is a simple method for the identification of clinically important, similar morphotypes of Aspergillus spp. within the section Fumigati.

Evidence-based health care: its place within clinical governance.

PubMed

McSherry, R; Haddock, J

This article explores the principles of evidence-based practice and its role in achieving quality improvements within the clinical governance framework advocated by the recent White Papers 'The New NHS: Modern, Dependable' (Department of Health (DoH), 1997) and 'A First Class Service: Quality in the New NHS' (DoH, 1998a). Within these White Papers there is an emphasis on improving quality of care, treatment and services through employing the principles of clinical governance. A major feature of clinical governance is guaranteeing quality to the public and the NHS, and ensuring that clinical, managerial and educational practice is based on scientific evidence. This article also examines what evidence-based practice is and what processes are required to promote effective healthcare interventions. The authors also look at how clinical governance relates to other methods/systems involved in clinical effectiveness. Finally, the importance for nurses and other healthcare professionals of familiarizing themselves with the development of critical appraisal skills, and their implications for developing evidence-based practice, is emphasized.

What every teacher needs to know about clinical reasoning.

PubMed

Eva, Kevin W

2005-01-01

One of the core tasks assigned to clinical teachers is to enable students to sort through a cluster of features presented by a patient and accurately assign a diagnostic label, with the development of an appropriate treatment strategy being the end goal. Over the last 30 years there has been considerable debate within the health sciences education literature regarding the model that best describes how expert clinicians generate diagnostic decisions. The purpose of this essay is to provide a review of the research literature on clinical reasoning for frontline clinical teachers. The strengths and weaknesses of different approaches to clinical reasoning will be examined using one of the core divides between various models (that of analytic (i.e. conscious/controlled) versus non-analytic (i.e. unconscious/automatic) reasoning strategies) as an orienting framework. Recent work suggests that clinical teachers should stress the importance of both forms of reasoning, thereby enabling students to marshal reasoning processes in a flexible and context-specific manner. Specific implications are drawn from this overview for clinical teachers.

The Gut Microbiome as Therapeutic Target in Central Nervous System Diseases: Implications for Stroke.

PubMed

Winek, Katarzyna; Dirnagl, Ulrich; Meisel, Andreas

2016-10-01

Research on commensal microbiota and its contribution to health and disease is a new and very dynamically developing field of biology and medicine. Recent experimental and clinical investigations underscore the importance of gut microbiota in the pathogenesis and course of stroke. Importantly, microbiota may influence the outcome of cerebral ischemia by modulating central nervous system antigen-specific immune responses. In this review we summarize studies linking gut microbiota with physiological function and disorders of the central nervous system. Based on these insights we speculate about targeting the gut microbiome in order to treat stroke.

The Important Role of Halogen Bond in Substrate Selectivity of Enzymatic Catalysis

NASA Astrophysics Data System (ADS)

Jiang, Shuiqin; Zhang, Lujia; Cui, Dongbin; Yao, Zhiqiang; Gao, Bei; Lin, Jinping; Wei, Dongzhi

2016-10-01

The use of halogen bond is widespread in drug discovery, design, and clinical trials, but is overlooked in drug biosynthesis. Here, the role of halogen bond in the nitrilase-catalyzed synthesis of ortho-, meta-, and para-chlorophenylacetic acid was investigated. Different distributions of halogen bond induced changes of substrate binding conformation and affected substrate selectivity. By engineering the halogen interaction, the substrate selectivity of the enzyme changed, with the implication that halogen bond plays an important role in biosynthesis and should be used as an efficient and reliable tool in enzymatic drug synthesis.

Informativeness of Self-Reports of ADHD Symptoms in Monitoring Response to Stimulant Treatment in Clinically Referred Adults With ADHD.

PubMed

Biederman, Joseph; Fitzgerald, Maura; Spencer, Thomas J; Adler, Lenard A; Abrams, Jessica; Biederman, Itai; Faraone, Stephen V

2018-05-01

To investigate the informativeness of self-reports of ADHD symptoms in adults with ADHD in the clinical setting. Subjects were clinically referred adults aged 19 years to 67 years of age of both sexes ( N = 54). All subjects were on stable doses of stimulant and were considered responders to treatment. ADHD symptoms were assessed using the ADHD Investigator Symptom Rating Scale (AISRS) and the ADHD Self-Report Scale (ASRS). Spearman's rank correlations were used to assess the correlations between clinician-assessed ADHD and patients' self-reports. Spearman's rank correlation analysis found evidence of a strong, positive association between total scores on the AISRS and the ASRS ( rs = .65, df = 52, p< .001). Results have important implications for the management and monitoring of treatment response in the clinical setting through patients' self-report.

Dental findings and oral health status in patients with mucopolysaccharidosis: a case series.

PubMed

Antunes, Lívia Azeredo Alves; Nogueira, Ana Paula Barreto; Castro, Glória Fernanda; Ribeiro, Márcia Gonçalves; de Souza, Ivete Pomarico Ribeiro

2013-01-01

To present a mucopolysaccharidosis (MPS) case series evaluating oral manifestations (clinical and radiographic), oral health status and discussing its implications. All patients with MPS attending the Genetics clinic/Brazil were evaluated by means of anamnesis, clinical and radiographic examinations. The final sample consisted of 12 subjects (nine males and three females), with ages ranging from 3-31 years old. Concerning oral health, it was observed high levels of caries and periodontal problems. About oral manifestations, this study clinically observed more cases of delayed tooth eruption, thickness of alveolar process and thick lips. Radiographically, it was observed alterations on condyle, mandibular ramus and joint fossa. The dental changes in MPS population are high and consequently it is important to know them for differential diagnoses, early treatment intervention, prevention and education of both patients and parents/caregivers about oral health.

The Role of Attachment Behaviors in the Link between Relationship Satisfaction and Depression in Clinical Couples: Implications for Clinical Practice.

PubMed

Novak, Joshua R; Sandberg, Jonathan G; Davis, Stephanie Y

2017-04-01

Using dyadic, clinical data from 104 couples in committed relationships, the purpose of this study was to determine whether relationship satisfaction was associated with depression through perceived partner attachment behaviors-accessibility, responsiveness, and engagement-for both men and women. We found that one's satisfaction in the relationship was the lens through which they viewed their partner's attachment behaviors and-women's relationship satisfaction was the lens through which her male partner viewed her attachment behaviors. Finally, women's relationship satisfaction is associated with both individuals' depression through her perceived partner's accessibility, responsiveness, and engagement. The findings from this study are important because they provide clinically relevant and mutable constructs in which clinicians can intervene at an attachment level in distressed marriages with depressed partners. © 2016 American Association for Marriage and Family Therapy.

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

Alzheimer Disease

PubMed Central

Apostolova, Liana G.

2016-01-01

ABSTRACT Purpose of Review: This article discusses the recent advances in the diagnosis and treatment of Alzheimer disease (AD). Recent Findings: In recent years, significant advances have been made in the fields of genetics, neuroimaging, clinical diagnosis, and staging of AD. One of the most important recent advances in AD is our ability to visualize amyloid pathology in the living human brain. The newly revised criteria for diagnosis of AD dementia embrace the use for biomarkers as supportive evidence for the underlying pathology. Guidelines for the responsible use of amyloid positron emission tomography (PET) have been developed, and the clinical and economic implications of amyloid PET imaging are actively being explored. Summary: Our improved understanding of the clinical onset, progression, neuroimaging, pathologic features, genetics, and other risk factors for AD impacts the approaches to clinical diagnosis and future therapeutic interventions. PMID:27042902

Myeloid derived suppressor cells in cancer: therapeutic, predictive, and prognostic implications

PubMed Central

Diaz-Montero, C. Marcela; Finke, Jim; Montero, Alberto J.

2014-01-01

Immune evasion is a hallmark of cancer. While, there are multiple different mechanisms that cancer cells employ, myeloid deriver suppressor cells (MDSCs) are one of the key drivers of tumor mediated immune evasion. MDSCs begin as myeloid cells recruited to the tumor microenvironment where they are transformed into potent immunosuppressive cells. Our understanding of the clinical relevance of MDSCs in cancer patients, however has significantly lagged behind the preclinical literature in part due to the absence of a cognate molecule present in mice, as well as the considerable heterogeneity of MDSCs. However, if one evaluates the clinical literature through the filter of clinically robust endpoints, such as overall survival, three important phenotypes have emerged: promyelocytic, monocytic, and granulocytic. Based on these studies, MDSCs have clear prognostic importance in multiple solid tumors, and emerging data supports the utility of circulating MDSCs as a predictive marker for cancer immunotherapy, and even as an early leading marker for predicting clinical response to systemic chemotherapy in patients with advanced solid tumors. More recent preclinical data in immunosuppressed murine models suggest that MDSCs play an important role in tumor progression and the metastatic process that is independent of their immunosuppressive properties. Consequently, targeting MDSCs either in combination with cancer immunotherapy or independently as part of an approach to inhibit the metastatic process, appears to be a very clinically promising strategy. We review different approaches to target MDSCs that could potentially be tested in future clinical trials in cancer patients. PMID:24787291

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

Hope for a cure and altruism are the main motives behind participation in phase 3 clinical cancer trials.

PubMed

Godskesen, T; Hansson, M G; Nygren, P; Nordin, K; Kihlbom, U

2015-01-01

It is necessary to carry out randomised clinical cancer trials (RCTs) in order to evaluate new, potentially useful treatments for future cancer patients. Participation in clinical trials plays an important role in determining whether a new treatment is the best therapy or not. Therefore, it is important to understand on what basis patients decide to participate in clinical trials and to investigate the implications of this understanding for optimising the information process related to study participation. The aims of this study were to (1) describe motives associated with participation in RCTs, (2) assess if patients comprehend the information related to trial enrolment, and (3) describe patient experiences of trial participation. Questionnaires were sent to 96 cancer patients participating in one of nine ongoing clinical phase 3 trials at the Department of Oncology, Uppsala University Hospital in Sweden. Eighty-eight patients completed the questionnaire (response rate 92%); 95% of these were patients in adjuvant therapy and 5% participated in clinical trials on palliative care. Two main reasons for participation were identified: personal hope for a cure and altruism. Patients show adequate understanding of the information provided to them in the consent process and participation entails high patient satisfaction. © 2014 John Wiley & Sons Ltd.

Hypnotic Approaches for Chronic Pain Management

PubMed Central

Jensen, Mark P.; Patterson, David R.

2015-01-01

The empirical support for hypnosis for chronic pain management has flourished over the past two decades. Clinical trials show that hypnosis is effective for reducing chronic pain, although outcomes vary between individuals. The findings from these clinical trials also show that hypnotic treatments have a number of positive effects beyond pain control. Neurophysiological studies reveal that hypnotic analgesia has clear effects on brain and spinal-cord functioning that differ as a function of the specific hypnotic suggestions made, providing further evidence for the specific effects of hypnosis. The research results have important implications for how clinicians can help their clients experience maximum benefits from hypnosis and treatments that include hypnotic components. PMID:24547802

Intentional and inadvertent chemical contamination of food, water, and medication.

PubMed

MCKay, Charles; Scharman, Elizabeth J

2015-02-01

Numerous examples of chemical contamination of food, water, or medication have led to steps by regulatory agencies to maintain the safety of this critical social infrastructure and supply chain. Identification of contaminant site is important. Environmental testing and biomonitoring can define the nature and extent of the event and are useful for providing objective information, but may be unavailable in time for clinical care. Clinical diagnosis should be based on toxidrome recognition and assessment of public health implications. There are several resources available to assist and these can be accessed through regional poison control centers or local/state public health departments. Copyright © 2015 Elsevier Inc. All rights reserved.

Pulp-dentin biology in restorative dentistry. Part 1: normal structure and physiology.

PubMed

Mjör, I A; Sveen, O B; Heyeraas, K J

2001-06-01

Considerable knowledge has accumulated over the years on the structure and function of the dental pulp and dentin. Some of this knowledge has important clinical implications. This review, which is the first of seven articles, will be limited to those parts of the normal structure and physiology of the pulp and dentin that have been shown to result in, or are likely lead to, tissue reactions associated with the clinical treatment of these tissues. Although certain normal structures will be highlighted in some detail, a basic knowledge of pulpal and dentinal development and structure is a prerequisite for an understanding of this text.

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

Plagiarism and registered health professionals: navigating the borderlands between scholarly and professional misconduct.

PubMed

Wardle, Jon

2013-12-01

As access to published materials becomes more readily available, the ability to plagiarise material, deliberately or unwittingly has become easier than ever. This article explores important recent decisions in Australia and the United Kingdom regarding registered health practitioners who have engaged in plagiarism, both related and unrelated to their clinical practice, and explores the ways in which regulatory authorities in these countries have viewed scholarly misconduct committed by registered health professionals. This article also examines the implications of plagiarism for the registered health professions, and makes suggestions for strategies to reduce its influence and incidence in modern clinical practice.

Countertransference in Child and Adolescent Psychiatry-A Forgotten Concept?

PubMed Central

Rasic, Daniel

2010-01-01

Objectives: The purpose of this paper is to review the evolution of the concept of countertransference, its clinical utility and unique features in the child and adolescent psychiatry setting. Methods: This article employs a selective literature review of papers relevant to countertransference in general and in child and adolescent psychiatry. Results: Reviewed papers indicate that countertransference is a ubiquitous phenomenon in child and adolescent psychiatric practice and that it can have important clinical implications. Conclusions: Recognition and management of countertransference is a crucial skill in child and adolescent psychiatry. Recommendations are made regarding its incorporation in residency training and psychiatric practice. PMID:21037914

Mechanisms of Drug Resistance: Daptomycin Resistance

PubMed Central

Tran, Truc T.; Munita, Jose M.; Arias, Cesar A.

2016-01-01

Daptomycin (DAP) is a cyclic lipopeptide with in vitro activity against a variety of Gram-positive pathogens, including multidrug-resistant organisms. Since its introduction in clinical practice in 2003, DAP has become an important key front-line antibiotic for severe or deep-seated infections caused by Gram-positive organisms. Unfortunately, DAP-resistance (R) has been extensively documented in clinically important organisms such as Staphylococcus aureus, Enterococcus spp, and Streptococcus spp. Studies on the mechanisms of DAP-R in Bacillus subtilis and other Gram-positive bacteria indicate that the genetic pathways of DAP resistance are diverse and complex. However, a common phenomenon emerging from these mechanistic studies is that DAP-R is associated with important adaptive changes in cell wall and cell membrane homeostasis with critical changes in cell physiology. Findings related to these adaptive changes have offered novel insights into the genetics and molecular mechanisms of bacterial cell envelope stress response and the manner in which Gram-positive bacteria cope with the antimicrobial peptide attack and protect vital structures of the cell envelope such as the cell membrane. In this review, we will examine the most recent findings related to the molecular mechanisms of resistance to DAP in relevant Gram-positive pathogens and discuss the clinical implications for therapy against these important bacteria. PMID:26495887

Clinical decision-making and secondary findings in systems medicine.

PubMed

Fischer, T; Brothers, K B; Erdmann, P; Langanke, M

2016-05-21

Systems medicine is the name for an assemblage of scientific strategies and practices that include bioinformatics approaches to human biology (especially systems biology); "big data" statistical analysis; and medical informatics tools. Whereas personalized and precision medicine involve similar analytical methods applied to genomic and medical record data, systems medicine draws on these as well as other sources of data. Given this distinction, the clinical translation of systems medicine poses a number of important ethical and epistemological challenges for researchers working to generate systems medicine knowledge and clinicians working to apply it. This article focuses on three key challenges: First, we will discuss the conflicts in decision-making that can arise when healthcare providers committed to principles of experimental medicine or evidence-based medicine encounter individualized recommendations derived from computer algorithms. We will explore in particular whether controlled experiments, such as comparative effectiveness trials, should mediate the translation of systems medicine, or if instead individualized findings generated through "big data" approaches can be applied directly in clinical decision-making. Second, we will examine the case of the Riyadh Intensive Care Program Mortality Prediction Algorithm, pejoratively referred to as the "death computer," to demonstrate the ethical challenges that can arise when big-data-driven scoring systems are applied in clinical contexts. We argue that the uncritical use of predictive clinical algorithms, including those envisioned for systems medicine, challenge basic understandings of the doctor-patient relationship. Third, we will build on the recent discourse on secondary findings in genomics and imaging to draw attention to the important implications of secondary findings derived from the joint analysis of data from diverse sources, including data recorded by patients in an attempt to realize their "quantified self." This paper examines possible ethical challenges that are likely to be raised as systems medicine to be translated into clinical medicine. These include the epistemological challenges for clinical decision-making, the use of scoring systems optimized by big data techniques and the risk that incidental and secondary findings will significantly increase. While some ethical implications remain still hypothetical we should use the opportunity to prospectively identify challenges to avoid making foreseeable mistakes when systems medicine inevitably arrives in routine care.

Gastrointestinal Bleeding in Athletes.

PubMed

Eichner, E R

1989-05-01

In brief: Gastrointestinal (GI) bleeding is a troubling yet intriguing complication of distance running. This clinical overview traces our evolving understanding of the scope and importance of GI bleeding in runners and other athletes, and discusses the diverse causes, sites, and implications of exercise-related GI bleeding. It concludes with practical tips to prevent or mitigate this problem, including gradual conditioning, avoidance of prerace aspirin intake, and when indicated, therapy with antacids, H2 blockers, or iron.

Recovery of Herbaspirillum Species from Persons with Cystic Fibrosis▿

PubMed Central

Spilker, Theodore; Uluer, Ahmet Z.; Marty, Francisco M.; Yeh, Wendy W.; Levison, Julie H.; Vandamme, Peter; LiPuma, John J.

2008-01-01

Herbaspirillum species are not known to be human pathogens. We report on the identification of Herbaspirillum from cultures from 28 persons with cystic fibrosis (CF). Most isolates were initially identified as members of the Burkholderia cepacia complex. Although the role that these species play in lung disease in persons with CF is not known, their differentiation from other species is important and has serious implications for clinical care and patient well-being. PMID:18524958

Improving performance with clinical decision support.

PubMed

Brailer, D J; Goldfarb, S; Horgan, M; Katz, F; Paulus, R A; Zakrewski, K

1996-07-01

CADU/CIS (Clinical and Administrative Decision-support Utility and Clinical Information System) is a clinical decision-support workstation that allows large volumes of clinical information systems data to be analyzed in a timely and user-friendly fashion. CARE PROCESS MEASUREMENT: For any given disease, subgroups of patients are identified, and automated, customized "clinical pathways" are generated. For each subgroup, the best practice norms for use of test and therapies are identified. Practice style variations are then compared to outcomes to focus inquiry on decisions that significantly affect outcomes. INTESTINAL OBSTRUCTION: Graduate Health Systems, a multisite integrated provider in the Philadelphia area, has used CADU/CIS to improve quality problems, reduce treatment-intensity variations, and improve clinical participation in care process evaluation and decision making. A task force selected intestinal obstruction without hernia as its first study because of the related high-volume and high-morbidity complications. Use of a ten-step method for clinical performance improvement showed that the intravenous administration of unnecessary fluids to 104 patients with intestinal obstruction induced congestive heart failure (CHF) in 5 patients. Task force members and other practicing physicians are now developing guidelines and other interventions aimed at fluid use. Indeed, the task force used CADU/CIS to identify an additional 250 patients in one year whose conditions were complicated by CHF. A clinical decision support tool can be instrumental in detecting problems with important clinical and economic implications, identifying their important underlying causes, tracking the associated tests and therapies, and monitoring interventions.

Animal Research on Nicotine Reduction: Current Evidence and Research Gaps.

PubMed

Smith, Tracy T; Rupprecht, Laura E; Denlinger-Apte, Rachel L; Weeks, Jillian J; Panas, Rachel S; Donny, Eric C; Sved, Alan F

2017-09-01

A mandated reduction in the nicotine content of cigarettes may improve public health by reducing the prevalence of smoking. Animal self-administration research is an important complement to clinical research on nicotine reduction. It can fill research gaps that may be difficult to address with clinical research, guide clinical researchers about variables that are likely to be important in their own research, and provide policy makers with converging evidence between clinical and preclinical studies about the potential impact of a nicotine reduction policy. Convergence between clinical and preclinical research is important, given the ease with which clinical trial participants can access nonstudy tobacco products in the current marketplace. Herein, we review contributions of preclinical animal research, with a focus on rodent self-administration, to the science of nicotine reduction. Throughout this review, we highlight areas where clinical and preclinical research converge and areas where the two differ. Preclinical research has provided data on many important topics such as the threshold for nicotine reinforcement, the likelihood of compensation, moderators of the impact of nicotine reduction, the impact of environmental stimuli on nicotine reduction, the impact of nonnicotine cigarette smoke constituents on nicotine reduction, and the impact of nicotine reduction on vulnerable populations. Special attention is paid to current research gaps including the dramatic rise in alternative tobacco products, including electronic nicotine delivery systems (ie, e-cigarettes). The evidence reviewed here will be critical for policy makers as well as clinical researchers interested in nicotine reduction. This review will provide policy makers and clinical researchers interested in nicotine reduction with an overview of the preclinical animal research conducted on nicotine reduction and the regulatory implications of that research. The review also highlights the utility of preclinical research for research questions related to nicotine reduction. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Multiple attachments and group psychotherapy: implications for college counseling centers.

PubMed

Marmarosh, Cheri L

2009-10-01

A large body of literature has supported the application of attachment theory to the understanding of college student development and the process of individual psychotherapy. Despite group treatment being one of the major methods of intervention in college counseling centers, there has been very little research guided by attachment theory that has been applied to the area of group psychotherapy. Many current assessment instruments used in college counseling centers can be supported with attachment theory, and many group therapy interventions are aimed at facilitating secure working models of self, other, and groups. This paper explores the importance of personal and group attachments in group psychotherapy and specifically addresses implications for clinical training and research in university counseling centers.

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.

Germline genome-editing research and its socioethical implications.

PubMed

Ishii, Tetsuya

2015-08-01

Genetically modifying eggs, sperm, and zygotes ('germline' modification) can impact on the entire body of the resulting individual and on subsequent generations. With the advent of genome-editing technology, human germline gene modification is no longer theoretical. Owing to increasing concerns about human germline gene modification, a voluntary moratorium on human genome-editing research and/or the clinical application of human germline genome editing has recently been called for. However, whether such research should be suspended or encouraged warrants careful consideration. The present article reviews recent research on mammalian germline genome editing, discusses the importance of public dialogue on the socioethical implications of human germline genome-editing research, and considers the relevant guidelines and legislation in different countries. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phytochemical Profile of Brown Rice and Its Nutrigenomic Implications.

PubMed

Ravichanthiran, Keneswary; Ma, Zheng Feei; Zhang, Hongxia; Cao, Yang; Wang, Chee Woon; Muhammad, Shahzad; Aglago, Elom K; Zhang, Yihe; Jin, Yifan; Pan, Binyu

2018-05-23

Whole grain foods have been promoted to be included as one of the important components of a healthy diet because of the relationship between the regular consumption of whole-grain foods and reduced risk of chronic diseases. Rice is a staple food, which has been widely consumed for centuries by many Asian countries. Studies have suggested that brown rice is associated with a wide spectrum of nutrigenomic implications such as anti-diabetic, anti-cholesterol, cardioprotective and antioxidant. This is because of the presence of various phytochemicals that are mainly located in bran layers of brown rice. Therefore, this paper is a review of publications that focuses on the bioactive compounds and nutrigenomic implications of brown rice. Although current evidence supports the fact that the consumption of brown rice is beneficial for health, these studies are heterogeneous in terms of their brown rice samples used and population groups, which cause the evaluation to be difficult. Future clinical studies should focus on the screening of individual bioactive compounds in brown rice with reference to their nutrigenomic implications.

The Potential Role of Aurora Kinase Inhibitors in Haematological Malignancies

PubMed Central

Farag, Sherif S.

2011-01-01

Summary Aurora kinases play an important role in the control of the cell cycle and have been implicated in tumourigenesis in a number of cancers. Among the haematological malignancies, overexpression of Aurora kinases has been reported in acute myeloid leukaemia, chronic myeloid leukaemia, acute lymphoblastic leukaemia, multiple myeloma, aggressive non-Hodgkin lymphoma and Hodgkin lymphoma. A large number of Aurora kinase inhibitors are currently in different stages of clinical development. In addition to varying in their selectivity for the different Aurora kinases, some also have activity directed at other cellular kinases involved in important molecular pathways in cancer cells. This review summarizes the biology of Aurora kinases and discusses why they may be good therapeutic targets in different haematological cancers. We describe preclinical data that has served as the rationale for investigating Aurora kinase inhibitors in different haematological malignancies, and summarize published results from early phase clinical trials. While the anti-tumour effects of Aurora kinase inhibitors appear promising, we highlight important issues for future clinical research and suggest that the optimal use of these inhibitors is likely to be in combination with cytotoxic agents already in use for the treatment of various haematological cancers. PMID:21980926

Perspectives of optic nerve prostheses.

PubMed

Lane, Frank John; Nitsch, Kristian; Huyck, Margaret; Troyk, Philip; Schug, Ken

2016-01-01

A number of projects exist that are investigating the ability to restore visual percepts for individuals who are blind through a visual prosthesis. While many projects have reported the results from a technical basis, very little exists in the professional literature on the human experience of visual implant technology. The current study uses an ethnographic methodological approach to document the experiences of the research participants and study personnel of a optic nerve vision prosthesis project in Brussels, Belgium. The findings have implications for motivation for participating in clinical trials, ethical safeguards of participants and the role of the participant in a research study. Implications for Rehabilitation Rehabilitation practitioners are often solicited by prospective participants to assist in evaluating a clinical trial before making a decision about participation. Rehabilitation professionals should be aware that: The decision to participate in a clinical trial is ultimately up to the individual participant. However, participants should be aware that family members might experience stress from of a lack of knowledge about the research study. The more opportunities a participant has to share thoughts and feelings about the research study with investigators will likely result in a positive overall experience. Ethical safeguards put in place to protect the interests of an individual participant may have the opposite effect and create stress. Rehabilitation professionals can play an important role as participant advocates from recruitment through termination of the research study. Participant hope is an important component of participation in a research study. Information provided to participants by investigators during the consent process should be balanced carefully with potential benefits, so it does not destroy a participant's hope.

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.

Pharmacogenetics in Latin American populations: regulatory aspects, application to herbal medicine, cardiovascular and psychiatric disorders.

PubMed

Rodeiro, Idania; Remírez-Figueredo, Diadelis; García-Mesa, Milagros; Dorado, Pedro; LLerena, Adrián

2012-01-01

Meeting report of the "Second Symposium on Pharmacology of Cytochrome P450 and Transporters" organized by the Cuban Society of Pharmacology in collaboration with the European Society of Pharmacogenetics and Theranostics (ESPT) and the Ibero-American Network of Pharmacogenetics and Pharmacogenomics (www.ribef.com). The Symposium covered different topics on pharmacogenetics and its clinical implications, focusing on Latin-American populations. The activities of the ESPT were also presented and discussed. The topics addressed were regulatory aspects, the use of pharmacogenetics in pre-clinical research, herbal medicine, and natural products, ending with a discussion about translation into clinical practice, specifically for cardiovascular disorders and psychiatry. Finally, the implication for population diversity in Latin America was also discussed. The RIBEF initiative represents a promising step towards the inclusion of Latin American populations among those to benefit from the implementation of pharmacogenetics in clinical practice. Among current RIBEF activities, the CEIBA.FP Consortium aims to study the variability of pheno- and genotypes in Hispanics that are relevant to pharmacogenetics. For this purpose, populations from Mexico, Cuba, Nicaragua, Costa Rica, Ecuador, Colombia, Brasil, Perú, Chile, Uruguay, Argentina, Portugal, and Spain are currently being studied. The meeting's main conclusion was that population pharmacogenetic studies as well as academic clinical trials might need to be conducted in the different geographic locations/countries. This is important in order to improve drug safety, dosage recommendations, and pharmacovigilance programs, because environmental and ethnic factors vary across locations.

Multiple rare variants in the etiology of autism spectrum disorders

PubMed Central

Buxbaum, Joseph D.

2009-01-01

Recent studies in autism spectrum disorders (ASDs) support an important role for multiple rare variants in these conditions. This is a clinically important finding, as, with the demonstration that a significant proportion of ASDs are the result of rare, etiological genetic variants, it becomes possible to make use of genetic testing to supplement behavioral analyses for an earlier diagnosis. As it appears that earlier interventions in ASDs will produce better outcomes, the development of genetic testing to augment behaviorally based evaluations in ASDs holds promise for improved treatment. Furthermore, these rare variants involve synaptic and neuronal genes that implicate specific paihvi/ays, cells, and subcellular compartments in ASDs, which in turn will suggest novel therapeutic approaches in ASDs, Of particular recent interest are the synaptic cell adhesion and associated molecules, including neurexin 1, neuroligin 3 and 4, and SHANK3, which implicate glutamatergic synapse abnormalities in ASDs, In the current review we will overview the evidence for a genetic etiology for ASDs, and summarize recent genetic findings in these disorders. PMID:19432386

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

Distinguishing Mediational Models and Analyses in Clinical Psychology: Atemporal Associations Do Not Imply Causation.

PubMed

Winer, E Samuel; Cervone, Daniel; Bryant, Jessica; McKinney, Cliff; Liu, Richard T; Nadorff, Michael R

2016-09-01

A popular way to attempt to discern causality in clinical psychology is through mediation analysis. However, mediation analysis is sometimes applied to research questions in clinical psychology when inferring causality is impossible. This practice may soon increase with new, readily available, and easy-to-use statistical advances. Thus, we here provide a heuristic to remind clinical psychological scientists of the assumptions of mediation analyses. We describe recent statistical advances and unpack assumptions of causality in mediation, underscoring the importance of time in understanding mediational hypotheses and analyses in clinical psychology. Example analyses demonstrate that statistical mediation can occur despite theoretical mediation being improbable. We propose a delineation of mediational effects derived from cross-sectional designs into the terms temporal and atemporal associations to emphasize time in conceptualizing process models in clinical psychology. The general implications for mediational hypotheses and the temporal frameworks from within which they may be drawn are discussed. © 2016 Wiley Periodicals, Inc.

Sources influencing patients in their HIV medication decisions.

PubMed

Meredith, K L; Jeffe, D B; Mundy, L M; Fraser, V J

2001-02-01

The authors surveyed 202 patients (54.5% male; 62.4% African American) enrolled at St. Louis HIV clinics to identify the importance of various sources of influence in their HIV medication decisions. Physicians were the most important source for 122 (60.4%) respondents, whereas prayer was most important for 24 respondents (11.9%). In multivariate tests controlling for CD4 counts, Caucasian men were more likely than Caucasian women and African Americans of both genders to select a physician as the most important source. African Americans were more likely than Caucasians to mention prayer as the most important source. Caucasians and those rating physicians as the most important source were more likely to be using antiretroviral medications. Respondents identified multiple important influences-hence the potential for conflicting messages about HIV medications. These findings have implications for health education practices and behavioral research in the medical setting.

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.

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.

CAG repeat testing of androgen receptor polymorphism: is this necessary for the best clinical management of hypogonadism?

PubMed

Francomano, Davide; Greco, Emanuela A; Lenzi, Andrea; Aversa, Antonio

2013-10-01

It is controversial whether or not testing the length of the androgen receptor polymorphism in clinical practice is useful for correct diagnosis and treatment of hypogonadism. To describe the molecular and clinical implications of testing the length of the androgen receptor polymorphism for treatment of hypogonadism in both male and female subjects. A systematic Medline search was conducted using several terms related to and including the terms "androgen receptor," "CAG-repeat polymorphism," "male hypogonadism," "female hypogonadism," and "neurodegenerative disease." Clinical evidence that demonstrates the importance of CAG repeat number investigation in male and female hypogonadism. A thorough review of the clinical utility of CAG repeat polymorphism investigation in men and women with hypogonadism is presented. The role of AR CAG repeat number investigation in hypogonadism (male and female) is not yet established in the clinical practice. In both sexes, a role during clinical management of hormonal replacement therapies may be hypothesized, but the CAG repeat number's relationship with the presence or absence of hypogonadal symptoms remains unclear. Pharmacogenomic investigations of the AR polymorphism may be a future option to tailor testosterone titration individually and to better identify subjects as potentially more or less responsive to treatments; also, investigation may be important to individually predict beneficial and side effects in special subpopulations, specifically, obese men and postmenopausal women. © 2013 International Society for Sexual Medicine.

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.

Clinical implications of treating depressed older adults with SSRIs: possible risk of hyponatremia.

PubMed

Smith, Judith M

2010-04-01

Depression is a serious mental health problem in older adults. Some of the symptoms of depression include depressed mood, significant change in weight or appetite, changes in sleep patterns, a decrease in concentration and energy, and possible suicide. However, depression is a treatable illness, especially with the newer class of antidepressant agents, the selective serotonin reuptake inhibitors (SSRIs). One side effect of SSRI use includes hyponatremia, which is becoming an increasingly serious complication that may have harmful clinical ramifications. Older adults are especially at risk for hyponatremia and could experience serious consequences if left untreated. The purpose of this article is to use an individual example to demonstrate the clinical importance of detecting hyponatremia in older adults receiving SSRI treatment. Copyright 2010, SLACK Incorporated.

Does intuition have a role in psychiatric diagnosis?

PubMed

Srivastava, Anil; Grube, Michael

2009-06-01

Psychiatric diagnosis is invariably guided by self-report. When such self-report is questioned, reliance on formalized testing predominates. The situation is less certain, however, when such methods and clinical "feel", or intuition, conflict. While many argue for the supremacy of actuarial methods, fields such as Management have increasingly emphasized the importance of intuition; Psychiatry, although with few objective tests and reliance on the clinical encounter, offers surprisingly few answers. We explore here the use of intuition in decision-making through a case example and suggest that it is not inferior to other diagnostic methods: intuition should be used to suggest, guide, and modify psychiatric diagnosis. Mostly, there is a need for greater discussion among Psychiatrists including consideration to the clinical, legal, and ethical implications of the use of intuition in psychiatric decision-making.

Basic science right, not basic science lite: medical education at a crossroad.

PubMed

Fincher, Ruth-Marie E; Wallach, Paul M; Richardson, W Scott

2009-11-01

This perspective is a counterpoint to Dr. Brass' article, Basic biomedical sciences and the future of medical education: implications for internal medicine. The authors review development of the US medical education system as an introduction to a discussion of Dr. Brass' perspectives. The authors agree that sound scientific foundations and skill in critical thinking are important and that effective educational strategies to improve foundational science education should be implemented. Unfortunately, many students do not perceive the relevance of basic science education to clinical practice.The authors cite areas of disagreement. They believe it is unlikely that the importance of basic sciences will be diminished by contemporary directions in medical education and planned modifications of USMLE. Graduates' diminished interest in internal medicine is unlikely from changes in basic science education.Thoughtful changes in education provide the opportunity to improve understanding of fundamental sciences, the process of scientific inquiry, and translation of that knowledge to clinical practice.

Clinical and molecular characterisation of hyperinsulinaemic hypoglycaemia in infants born small-for-gestational age.

PubMed

Arya, Ved Bhushan; Flanagan, Sarah E; Kumaran, Anitha; Shield, Julian P; Ellard, Sian; Hussain, Khalid; Kapoor, Ritika R

2013-07-01

To characterise the phenotype and genotype of neonates born small-for-gestational age (SGA; birth weight <10th centile) who developed hyperinsulinaemic hypoglycaemia (HH). Clinical information was prospectively collected on 27 SGA neonates with HH, followed by sequencing of KCNJ11 and ABCC8. There was no correlation between the maximum glucose requirement and serum insulin levels. Serum insulin level was undetectable in five infants (19%) during hypoglycaemia. Six infants (22%) required diazoxide treatment >6 months. Normoglycaemia on diazoxide <5 mg/kg/day was a safe predictor of resolved HH. Sequencing of KCNJ11/ABCC8 did not identify any mutations. Serum insulin levels during hypoglycaemia taken in isolation can miss the diagnosis of HH. SGA infants may continue to have hypofattyacidaemic hypoketotic HH beyond the first few weeks of life. Recognition and treatment of this group of patients are important and may have important implications for neurodevelopmental outcome of these patients.

Five important advances in hematopathology.

PubMed

Shi, Min; Xiao, Ruobing; Woda, Bruce A; Yu, Hongbo

2014-03-01

Hematopathology is a dynamic field that has always been on the frontier of clinical research within the scope of pathology. Several recent developments in hematopathology will likely affect its practice clinically. To review 5 important recent advances in hematopathology: (1) detection and prognostic implication of MYC in diffuse large B-cell lymphomas, (2) determining origin and prognosis through immunoglobulin gene usage in mature B-cell neoplasms, (3)detecting minimal residual disease in multiple myeloma, (4) using genome-wide analysis in myelodysplastic syndromes, and (5) employing whole-genome sequencing in acute myeloid leukemias. Literature review and the authors' experiences in an academic center. These advances will bring hematopathology into a new molecular era and help us to better understand the molecular, pathologic mechanisms of lymphomas, leukemias, myelomas, and myelodysplastic syndromes. They will help us to identify diagnostic and prognostic markers and eventually provide new therapeutic targets and treatments for these diseases.

An anatomical study of arcuate foramen and its clinical implications: a case report.

PubMed

Afsharpour, Salman; Hoiriis, Kathryn T; Fox, R Bruce; Demons, Samuel

2016-01-01

The objective of this paper is to describe the relationship of the vertebral artery (VA) to the Atlas (C1) in the sub-occipital region in the presence of arcuate foramen; and discuss the clinical implications related to manual therapies and surgical implications related to screw placement. This study is an anatomical cadaveric case report of symmetrical bilateral lateral and dorsal arcuate foramina on the C1 dorsal arch. Out of 40 cadavers that were available for use in teaching anatomy in the university setting, three presented with anomalies of the C1 dorsal arch. The sub-occipital regions were skillfully prosected to preserve related structures, especially VAs, sub-occipital and greater occipital nerves. Visual observations, photographs, measurements, and radiographic examinations were performed between January 15, 2014 and August 25, 2014. One cadaver (Specimen A) presented with complete bilateral ossified arcuate foramina, and two presented with partial ossification of the atlanto-occipital membrane. Specimen A presented the bilateral anomaly which is almost symmetrical. The VAs were found passing through double foramina (lateral and dorsal) on each side. Arcuate foramina have been shown to be commonly found anomalies with highly variable shapes and sizes, even in the same individual with a bilateral condition. This study found a rare type of the anomaly associated with the C1 dorsal arch, which protected the VA against manual pressure. However, VA, in this case, would be more susceptible to dissection. The presence of the arcuate foramen would also complicate screw placement during surgery. Clinical pre-screening for signs of vertebrobasilar insufficiency is important for chiropractic and manual therapies.

[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.

An analysis of clinical reasoning through a recent and comprehensive approach: the dual-process theory.

PubMed

Pelaccia, Thierry; Tardif, Jacques; Triby, Emmanuel; Charlin, Bernard

2011-03-14

Clinical reasoning plays a major role in the ability of doctors to make diagnoses and decisions. It is considered as the physician's most critical competence, and has been widely studied by physicians, educationalists, psychologists and sociologists. Since the 1970s, many theories about clinical reasoning in medicine have been put forward. This paper aims at exploring a comprehensive approach: the "dual-process theory", a model developed by cognitive psychologists over the last few years. After 40 years of sometimes contradictory studies on clinical reasoning, the dual-process theory gives us many answers on how doctors think while making diagnoses and decisions. It highlights the importance of physicians' intuition and the high level of interaction between analytical and non-analytical processes. However, it has not received much attention in the medical education literature. The implications of dual-process models of reasoning in terms of medical education will be discussed.

Clinical implications of infection with a novel metastrongyloid species in the red panda (Ailurus fulgens).

PubMed

Willesen, Jakob L; Meyland-Smith, Frederik; Wiinberg, Bo; Monrad, Jesper; Bertelsen, Mads F

2012-06-01

In a recent survey, 30% of the European red panda (Ailurus fulgens) population was found to be infected with a newly discovered metastrongyloid nematode. In a following prospective study, four naturally infected captive-bred red pandas infected with this parasite were examined and compared with two uninfected control animals. On clinical examination, no abnormalities were detected with respect to vital parameters and cardiovascular system in all six examined animals. Similarly, few and nonspecific changes were recorded on serum biochemistry. No changes on pulmonary pattern were noted on thoracic radiographs. Vertebral heart scores were between 7.2 to 8.6, and no difference was noted between infected and control animals. Two animals had slightly prolonged clotting time and reaction time on thromboelastography but not likely to be of clinical relevance. In conclusion, infection with the newly identified metastrongyloid nematode in the red pandas seems to have little or no clinical importance.

Clinical research data sharing: what an open science world means for researchers involved in evidence synthesis.

PubMed

Ross, Joseph S

2016-09-20

The International Committee of Medical Journal Editors (ICMJE) recently announced a bold step forward to require data generated by interventional clinical trials that are published in its member journals to be responsibly shared with external investigators. The movement toward a clinical research culture that supports data sharing has important implications for the design, conduct, and reporting of systematic reviews and meta-analyses. While data sharing is likely to enhance the science of evidence synthesis, facilitating the identification and inclusion of all relevant research, it will also pose key challenges, such as requiring broader search strategies and more thorough scrutiny of identified research. Furthermore, the adoption of data sharing initiatives by the clinical research community should challenge the community of researchers involved in evidence synthesis to follow suit, including the widespread adoption of systematic review registration, results reporting, and data sharing, to promote transparency and enhance the integrity of the research process.

Next generation sequencing--implications for clinical practice.

PubMed

Raffan, Eleanor; Semple, Robert K

2011-01-01

Genetic testing in inherited disease has traditionally relied upon recognition of the presenting clinical syndrome and targeted analysis of genes known to be linked to that syndrome. Consequently, many patients with genetic syndromes remain without a specific diagnosis. New 'next-generation' sequencing (NGS) techniques permit simultaneous sequencing of enormous amounts of DNA. A slew of research publications have recently demonstrated the tremendous power of these technologies in increasing understanding of human genetic disease. These approaches are likely to be increasingly employed in routine diagnostic practice, but the scale of the genetic information yielded about individuals means that caution must be exercised to avoid net harm in this setting. Use of NGS in a research setting will increasingly have a major but indirect beneficial impact on clinical practice. However, important technical, ethical and social challenges need to be addressed through informed professional and public dialogue before it finds its mature niche as a direct tool in the clinical diagnostic armoury.

Developing a guideline for clinical trial protocol content: Delphi consensus survey

PubMed Central

2012-01-01

Background Recent evidence has highlighted deficiencies in clinical trial protocols, having implications for many groups. Existing guidelines for randomized clinical trial (RCT) protocol content vary substantially and most do not describe systematic methodology for their development. As one of three prespecified steps for the systematic development of a guideline for trial protocol content, the objective of this study was to conduct a three-round Delphi consensus survey to develop and refine minimum content for RCT protocols. Methods Panellists were identified using a multistep iterative approach, met prespecified minimum criteria and represented key stakeholders who develop or use clinical trial protocols. They were asked to rate concepts for importance in a minimum set of items for RCT protocols. The main outcome measures were degree of importance (scale of 1 to 10; higher scores indicating higher importance) and level of consensus for items. Results were presented as medians, interquartile ranges, counts and percentages. Results Ninety-six expert panellists participated in the Delphi consensus survey including trial investigators, methodologists, research ethics board members, funders, industry, regulators and journal editors. Response rates were between 88 and 93% per round. Overall, panellists rated 63 of 88 concepts of high importance (of which 50 had a 25th percentile rating of 8 or greater), 13 of moderate importance (median 6 or 7) and 12 of low importance (median less than or equal to 5) for minimum trial protocol content. General and item-specific comments and subgroup results provided valuable insight for further discussions. Conclusions This Delphi process achieved consensus from a large panel of experts from diverse stakeholder groups on essential content for RCT protocols. It also highlights areas of divergence. These results, complemented by other empirical research and consensus meetings, are helping guide the development of a guideline for protocol content. PMID:23006145

Measuring psychological flexibility in medical students and residents: a psychometric analysis

PubMed Central

Palladino, Christie L.; Ange, Brittany; Richardson, Deborah S.; Casillas, Rhonda; Decker, Matt; Gillies, Ralph A.; House, Amy; Rollock, Michael; Salazar, William H.; Waller, Jennifer L.; Zeidan, Ronnie; Stepleman, Lara

2013-01-01

Purpose Psychological flexibility involves mindful awareness of our thoughts and feelings without allowing them to prohibit acting consistently with our values and may have important implications for patient-centered clinical care. Although psychological flexibility appears quite relevant to the training and development of health care providers, prior research has not evaluated measures of psychological flexibility in medical learners. Therefore, we investigated the validity of our learners’ responses to three measures related to psychological flexibility. Methods Fourth-year medical students and residents (n=275) completed three measures of overlapping aspects of psychological flexibility: (1) Acceptance and Action Questionnaire-II (AAQ-II); (2) Cognitive Fusion Questionnaire (CFQ); and (3) Mindful Attention and Awareness Questionnaire (MAAS). We evaluated five aspects of construct validity: content, response process, internal structure, relationship with other variables, and consequences. Results We found good internal consistency for responses on the AAQ (α=0.93), MAAS (α=0.92), and CFQ (α=0.95). Factor analyses demonstrated a reasonable fit to previously published factor structures. As expected, scores on all three measures were moderately correlated with one another and with a measure of life satisfaction (p<0.01). Conclusion Our findings provide preliminary evidence supporting validity of the psychological flexibility construct in a medical education sample. As psychological flexibility is a central concept underlying self-awareness, this work may have important implications for clinical training and practice. PMID:23948496

The Human Microbiome and Understanding the 16S rRNA Gene in Translational Nursing Science.

PubMed

Ames, Nancy J; Ranucci, Alexandra; Moriyama, Brad; Wallen, Gwenyth R

As more is understood regarding the human microbiome, it is increasingly important for nurse scientists and healthcare practitioners to analyze these microbial communities and their role in health and disease. 16S rRNA sequencing is a key methodology in identifying these bacterial populations that has recently transitioned from use primarily in research to having increased utility in clinical settings. The objectives of this review are to (a) describe 16S rRNA sequencing and its role in answering research questions important to nursing science; (b) provide an overview of the oral, lung, and gut microbiomes and relevant research; and (c) identify future implications for microbiome research and 16S sequencing in translational nursing science. Sequencing using the 16S rRNA gene has revolutionized research and allowed scientists to easily and reliably characterize complex bacterial communities. This type of research has recently entered the clinical setting, one of the best examples involving the use of 16S sequencing to identify resistant pathogens, thereby improving the accuracy of bacterial identification in infection control. Clinical microbiota research and related requisite methods are of particular relevance to nurse scientists-individuals uniquely positioned to utilize these techniques in future studies in clinical settings.

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.

Resilients, overcontrollers and undercontrollers: A systematic review of the utility of a personality typology method in understanding adult mental health problems.

PubMed

Bohane, Laura; Maguire, Nick; Richardson, Thomas

2017-11-01

The person-centred typological approach to personality makes the distinction between overcontrolled and undercontrolled personality types. This review systematically searched for research on the utility of these personality types in adult mental health. A total of 43 papers were included, which were divided broadly into cross-sectional studies, longitudinal studies and studies with clinical populations. Three personality types have been largely replicated in both normal and clinical populations: resilients, overcontrollers and undercontrollers. These types show utility in predicting long-term functioning and mental health, understanding heterogeneous personalities within clinical subgroups and have implications for treatment. Some disagreement on the number of personality types deemed replicable across samples and differing methodologies do exist, with some finding a dimensional approach to personality to have greater predictive utility. These personality types have been shown to be important in a number of mental health problems such as eating disorders, which may prove helpful in developing new psychological interventions. These studies point to the importance of overcontrolled personality types as well as undercontrolled in mental health. More research is needed with a greater range of clinical populations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Not lost in translation: Emerging clinical importance of the G protein-coupled estrogen receptor GPER.

PubMed

Barton, Matthias

2016-07-01

It has been 20years that the G protein-coupled estrogen receptor (GPER) was cloned as the orphan receptor GPR30 from multiple cellular sources, including vascular endothelial cells. Here, I will provide an overview of estrogen biology and the historical background leading to the discovery of rapid vascular estrogen signaling. I will also review the recent advances in the understanding of the mechanisms underlying GPER function, its role in physiology and disease, some of the currently available GPER-targeting drugs approved for clinical use such as SERMs (selective estrogen receptor modulators) and SERDs (selective estrogen receptor downregulators). Many of currently used drugs such as tamoxifen, raloxifene, or faslodex™/fulvestrant were discovered targeting GPER many years after they had been introduced to the clinics for entirely different purposes. This has important implications for the clinical use of these drugs and their modes of action, which I have termed 'reverse translational medicine'. In addition, environmental pollutants known as 'endocrine disruptors' have been found to bind to GPER. This article also discusses recent evidence in these areas as well as opportunities in translational clinical medicine and GPER research, including medical genetics, personalized medicine, prevention, and its theranostic use. Copyright © 2016 Elsevier Inc. All rights reserved.

Applying Bradford Hill's criteria for causation to neuropsychiatry: challenges and opportunities.

PubMed

van Reekum, R; Streiner, D L; Conn, D K

2001-01-01

Establishing an argument of causation is an important research activity with major clinical and scientific implications. Sir Austin Bradford Hill proposed criteria to establish such an argument. These criteria include the strength of the association, consistency, specificity, temporal sequence, biological gradient, biologic rationale, coherence, experimental evidence, and analogous evidence. These criteria are reviewed with the goal of facilitating an increase in rigor for establishing arguments of causation in neuropsychiatry. The challenges and opportunities related to these criteria in neuropsychiatry are reviewed, as are two important arguments for causation: one for poststroke depression and one for brain injury as a cause of psychiatric disorders.

Animal Models of Substance Abuse and Addiction: Implications for Science, Animal Welfare, and Society

PubMed Central

Lynch, Wendy J; Nicholson, Katherine L; Dance, Mario E; Morgan, Richard W; Foley, Patricia L

2010-01-01

Substance abuse and addiction are well recognized public health concerns, with 2 NIH institutes (the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism) specifically targeting this societal problem. As such, this is an important area of research for which animal experiments play a critical role. This overview presents the importance of substance abuse and addiction in society; reviews the development and refinement of animal models that address crucial areas of biology, pathophysiology, clinical treatments, and drug screening for abuse liability; and discusses some of the unique veterinary, husbandry, and IACUC challenges associated with these models. PMID:20579432

Fungicidal activity of tioconazole in relation to growth phase of Candida albicans and Candida parapsilosis.

PubMed Central

Beggs, W H

1984-01-01

It was shown that tioconazole possesses an important property not shared by ketoconazole and miconazole, its well-known relatives in the imidazole group of antifungal drugs. At a concentration of 3.8 X 10(-5) M, tioconazole, like miconazole, caused rapid 2- to 3-log reductions in CFU per milliliter when added to late-logarithmic-phase Candida albicans or Candida parapsilosis cells. Only tioconazole, however, exerted similar reductions when added to diluted stationary-phase cultures. This growth-phase-independent lethal action has important clinical implications and may explain the superior performance of tioconazole, which was observed in earlier comparative drug studies. PMID:6097174

A case of thymic Langerhans cell histiocytosis with diabetes insipidus as the first presentation.

PubMed

Chen, Xiaoyan; Huang, Xiaochun; Qiu, Yuan; Chen, Hanzhang; Fu, Yingyu; Li, Xinchun

2013-03-01

Langerhans cell histiocytosis (LCH) is an idiopathic group of reactive proliferative diseases linked to aberrant immunity, pathologically characterized by clonal proliferation of Langerhans cells. LCH rarely involves the thymus. We report a case of thymic LCH with diabetes insipidus as the first presentation, without evidence of myasthenia gravis and without evidenced involvement of the skin, liver, spleen, bones, lungs and superficial lymph nodes. This present case may have important clinical implications. In screening for LCH lesions, attention should be attached to rarely involved sites in addition to commonly involved organs. Follow-up and imageological examination are very important to a final diagnosis.

Animal models of substance abuse and addiction: implications for science, animal welfare, and society.

PubMed

Lynch, Wendy J; Nicholson, Katherine L; Dance, Mario E; Morgan, Richard W; Foley, Patricia L

2010-06-01

Substance abuse and addiction are well recognized public health concerns, with 2 NIH institutes (the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism) specifically targeting this societal problem. As such, this is an important area of research for which animal experiments play a critical role. This overview presents the importance of substance abuse and addiction in society; reviews the development and refinement of animal models that address crucial areas of biology, pathophysiology, clinical treatments, and drug screening for abuse liability; and discusses some of the unique veterinary, husbandry, and IACUC challenges associated with these models.

In defence of auscultation: a glorious future?

PubMed Central

Thompson, W Reid

2017-01-01

Auscultation of the heart using a simple stethoscope continues to be a central aspect of the cardiovascular examination despite declining proficiency and availability of competing technologies such as hand-held ultrasound. In the ears and mind of a trained cardiologist, heart sounds can provide important information to help screen for certain diseases such as valvar lesions and many congenital defects. Using emerging technology, auscultation is poised to undergo a transformation that will simultaneously improve the teaching and evaluation of this important clinical skill and create a new generation of smart stethoscopes, capable of assisting the clinician in quickly and confidently screening for heart disease. These developments have important implications for global health, screening of athletes and recognition of congenital heart disease. PMID:28243316

Continuing Need for Sexually Transmitted Disease Clinics After the Affordable Care Act.

PubMed

Hoover, Karen W; Parsell, Bradley W; Leichliter, Jami S; Habel, Melissa A; Tao, Guoyu; Pearson, William S; Gift, Thomas L

2015-11-01

We assessed the characteristics of sexually transmitted disease (STD) clinic patients, their reasons for seeking health services in STD clinics, and their access to health care in other venues. In 2013, we surveyed persons who used publicly funded STD clinics in 21 US cities with the highest STD morbidity. Of the 4364 STD clinic patients we surveyed, 58.5% were younger than 30 years, 72.5% were non-White, and 49.9% were uninsured. They visited the clinic for STD symptoms (18.9%), STD screening (33.8%), and HIV testing (13.6%). Patients chose STD clinics because of walk-in, same-day appointments (49.5%), low cost (23.9%), and expert care (8.3%). Among STD clinic patients, 60.4% had access to another type of venue for sick care, and 58.5% had access to another type of venue for preventive care. Most insured patients (51.6%) were willing to use insurance to pay for care at the STD clinic. Despite access to other health care settings, patients chose STD clinics for sexual health care because of convenient, low-cost, and expert care. Policy Implication. STD clinics play an important role in STD prevention by offering walk-in care to uninsured patients.

Human genetics after the bomb: Archives, clinics, proving grounds and board rooms.

PubMed

Lindee, Susan

2016-02-01

In this paper I track the history of post-1945 human genetics and genomics emphasizing the importance of ideas about risk to the scientific study and medical management of human heredity. Drawing on my own scholarship as it is refracted through important new work by other scholars both junior and senior, I explore how radiation risk and then later disease risk mattered to the development of genetics and genomics, particularly in the United States. In this context I excavate one of the central ironies of post-war human genetics: while studies of DNA as the origin and cause of diseases have been lavishly supported by public institutions and private investment around the world, the day-to-day labor of intensive clinical innovation has played a far more important role in the actual human experience of genetic disease and genetic risk for affected families. This has implications for the archival record, where clinical interactions are less readily accessible to historians. This paper then suggests that modern genomics grew out of radiation risk; that it was and remains a risk assessment science; that it is temporally embedded as a form of both prediction and historical reconstruction; and that it has become a big business focused more on risk and prediction (which can be readily marketed) than on effective clinical intervention. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Flow Dynamics of Contrast Dispersion in the Aorta

NASA Astrophysics Data System (ADS)

Eslami, Parastou; Seo, Jung-Hee; Chen, Marcus; Mittal, Rajat

2016-11-01

The time profile of the contrast concentration or arterial input function (AIF) has many fundamental clinical implications and is of importance for many imaging modalities and diagnosis such as MR perfusion, CT perfusion and CT angiography (CTA). Contrast dispersion in CTA has been utilized to develop a novel method- Transluminal Attenuation Flow Encoding (TAFE)- to estimate coronary blood flow (CBF). However, in clinical practice, AIF is only available in the descending aorta and is used as a surrogate of the AIF at the coronary ostium. In this work we use patient specific computational models of the complete aorta to investigate the fluid dynamics of contrast dispersion in the aorta. The simulation employs a realistic kinematic model of the aortic valve and the dispersion patterns are correlated with the complex dynamics of the pulsatile flow in the curved aorta. The simulations allow us to determine the implications of using the descending aorta AIF as a surrogate for the AIF at the coronary ostium. PE is supported by the NIH Individual Partnership Program. -/abstract- Category: 4.7.1: Biological fluid dynamics: Physiological - Cardiovasc This work was done at Johns Hopkins University.

A Neurophysiological and Neuropsychological Consideration of Mindful Movement: Clinical and Research Implications

PubMed Central

Russell, Tamara Anne; Arcuri, Silvia Maria

2015-01-01

In this article, we present ideas related to three key aspects of mindfulness training: the regulation of attention via noradrenaline, the importance of working memory and its various components (particularly the central executive and episodic buffer), and the relationship of both of these to mind-wandering. These same aspects of mindfulness training are also involved in the preparation and execution of movement and implicated in the pathophysiology of psychosis. We argue that by moving in a mindful way, there may be an additive effect of training as the two elements of the practice (mindfulness and movement) independently, and perhaps synergistically, engage common underlying systems (the default mode network). We discuss how working with mindful movement may be one route to mindfulness training for individuals who would struggle to sit still to complete the more commonly taught mindfulness practices. Drawing on our clinical experience working with individuals with severe and enduring mental health conditions, we show the real world application of these ideas and how they can be used to help those who are suffering and for whom current treatments are still far from adequate. PMID:26074800

[Clinical implications of polycystic ovary syndrome].

PubMed

Dravecká, Ingrid

Polycystic ovary syndrome (PCOS) is a heterogeneous and complex endocrine disease which among the female population belongs to the most widespread endocrinopathies and it is the most frequent cause of hyperthyroidism, anticoagulation and infertility. Insulin resistance is one of the important diabetology factors impacting hyperglycaemia in a majority of women with PCOS (60-80 %). Clinical expressions of PCOS include reproduction disorders, metabolic characteristics and psychological implications. Reproduction disorders include hyperthyroidism, menstruation cycle disorders, infertility and pregnancy complications as well as early abortions, gestational diabetes and pregnancy induced hypertension. Long-term metabolic risks of PCOS include type 2 diabetes mellitus, dyslipidemia, arterial hypertension and endothelial dysfunction. The available data confirms higher incidence of cardiovascular diseases in women with PCOS. In particular among obese women PCOS is more frequently associated with non-alcoholic hepatic steatosis, sleep apnoea syndrome and endometrial cancer. The literature includes some controversial data about the relationship between PCOS and autoimmunity. Women with PCOS are more prone to suffer from insufficient confidence with higher incidence of anxiety, depression, bipolar disorder and eating disorders. autoimmunity - diabetes mellitus - pregnancy - insulin resistance - metabolic syndrome - menstrual disorders - polycystic ovary syndrome.

Mitochondrial iron-sulfur cluster biogenesis from molecular understanding to clinical disease

PubMed Central

Alfadhel, Majid; Nashabat, Marwan; Ali, Qais Abu; Hundallah, Khalid

2017-01-01

Iron–sulfur clusters (ISCs) are known to play a major role in various protein functions. Located in the mitochondria, cytosol, endoplasmic reticulum and nucleus, they contribute to various core cellular functions. Until recently, only a few human diseases related to mitochondrial ISC biogenesis defects have been described. Such diseases include Friedreich ataxia, combined oxidative phosphorylation deficiency 19, infantile complex II/III deficiency defect, hereditary myopathy with lactic acidosis and mitochondrial muscle myopathy, lipoic acid biosynthesis defects, multiple mitochondrial dysfunctions syndromes and non ketotic hyperglycinemia due to glutaredoxin 5 gene defect. Disorders of mitochondrial import, export and translation, including sideroblastic anemia with ataxia, EVEN-PLUS syndrome and mitochondrial complex I deficiency due to nucleotide-binding protein-like protein gene defect, have also been implicated in ISC biogenesis defects. With advances in next generation sequencing technologies, more disorders related to ISC biogenesis defects are expected to be elucidated. In this article, we aim to shed the light on mitochondrial ISC biogenesis, related proteins and their function, pathophysiology, clinical phenotypes of related disorders, diagnostic approach, and future implications. PMID:28064324

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.

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.

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.

Differences among skeletal muscle mass indices derived from height-, weight-, and body mass index-adjusted models in assessing sarcopenia

PubMed Central

Kim, Kyoung Min; Jang, Hak Chul; Lim, Soo

2016-01-01

Aging processes are inevitably accompanied by structural and functional changes in vital organs. Skeletal muscle, which accounts for 40% of total body weight, deteriorates quantitatively and qualitatively with aging. Skeletal muscle is known to play diverse crucial physical and metabolic roles in humans. Sarcopenia is a condition characterized by significant loss of muscle mass and strength. It is related to subsequent frailty and instability in the elderly population. Because muscle tissue is involved in multiple functions, sarcopenia is closely related to various adverse health outcomes. Along with increasing recognition of the clinical importance of sarcopenia, several international study groups have recently released their consensus on the definition and diagnosis of sarcopenia. In practical terms, various skeletal muscle mass indices have been suggested for assessing sarcopenia: appendicular skeletal muscle mass adjusted for height squared, weight, or body mass index. A different prevalence and different clinical implications of sarcopenia are highlighted by each definition. The discordances among these indices have emerged as an issue in defining sarcopenia, and a unifying definition for sarcopenia has not yet been attained. This review aims to compare these three operational definitions and to introduce an optimal skeletal muscle mass index that reflects the clinical implications of sarcopenia from a metabolic perspective. PMID:27334763

Last wills and testaments in a large sample of suicide notes: implications for testamentary capacity.

PubMed

Sinyor, Mark; Schaffer, Ayal; Hull, Ian; Peisah, Carmelle; Shulman, Kenneth

2015-01-01

The leaving of a will prior to death by suicide is a relatively unexplored area. To determine the frequency and details of will content in suicide notes. Coroner records for 1565 deaths by suicide in Toronto (2003-2009) were reviewed for (a) will content and (b) the presence of depression, psychotic illness, dementia and intoxication prior to death. In total, 59 (20.7%) of 285 available suicide notes were found to have will content. Of those who left a will, 43 (72.9%) were reported to have a major mood or psychotic disorder, but none had dementia. Fifteen of 19 toxicology samples showed alcohol, sedative hypnotic/benzodiazepine, opioid and/or recreational drugs were present. A substantial minority of suicide notes may also include testamentary intent. The observed high rate of mental illness and substance use around the time of death has important clinical implications for understanding the mindset of people who die by suicide and hence also legal implications regarding testamentary capacity. Royal College of Psychiatrists.

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.

Ecocardiografía tridimensional. Nuevas perspectivas sobre la caracterización de la válvula mitral

PubMed Central

Solis, Jorge; Sitges, Marta; Levine, Robert A.; Hung, Judy

2010-01-01

Recent developments in three-dimensional echocardiography have made it possible to obtain images in real time, without the need for off-line reconstruction. These developments have enabled the technique to become an important tool for both research and daily clinical practice. A substantial proportion of the studies carried out using three-dimensional echocardiography have focused on the mitral valve, the pathophysiology of mitral valve disease and, in particular, functional mitral regurgitation. The aims of this article were to review the contribution of three-dimensional echocardiography to understanding of the functional anatomy of the mitral valve and to summarize the resulting clinical applications and therapeutic implications. PMID:19232192

[Diabetes mellitus in children: a heterogeneous disease].

PubMed

Rubio Cabezas, Oscar; Argente Oliver, Jesús

2007-04-28

Diabetes is one of the most common chronic diseases of childhood and adolescence. Type 1, or autoimmune diabetes accounts for more than 95% of cases. Nevertheless, over the past years it has become apparent that not all cases of diabetes presenting in children are autoimmune type 1. In these cases, the diagnosis is facilitated by the fact that many rare etiologies of diabetes are associated with specific clinical syndromes or a characteristic age of onset. In addition, molecular diagnosis is becoming increasingly available for several of these disorders. This review aims to provide the general physician with some important clues to make an accurate diagnosis in these patients and understand its implication in clinical management.

Historical Lessons in Translational Medicine: Cyclooxygenase Inhibition and P2Y12 Antagonism

PubMed Central

Fitzgerald, Desmond J.; FitzGerald, Garret A.

2013-01-01

The development of drugs that inhibit platelets has been driven by a combination of clinical insights, fundamental science and sheer luck. The process has evolved as the days of stumbling upon therapeutic gems like aspirin have long passed and have been replaced by an arduous process where a drug is designed to target a specific protein implicated in a well-characterized pathophysiological process. Or so we would like to believe. The development of antiplatelet therapy illustrates the importance of understanding the mechanisms of disease and the pharmacology of the compounds we develop, coupled with careful clinical experimentation and observation. And yes, still, a fair bit of luck. PMID:23287454

Cardiac Computed Tomography and Magnetic Resonance Imaging in the Evaluation of Mitral and Tricuspid Valve Disease: Implications for Transcatheter Interventions.

PubMed

Naoum, Christopher; Blanke, Philipp; Cavalcante, João L; Leipsic, Jonathon

2017-03-01

Transcatheter interventions to treat mitral and tricuspid valve disease are becoming increasingly available because of the growing number of elderly patients with significant comorbidities or high operative risk. Thorough clinical and imaging evaluation in these patients is essential. The latter involves both characterization of the mechanism and severity of valvular disease as well as determining the hemodynamic consequences and extent of ventricular remodeling, which is an important predictor of future outcomes. Moreover, an assessment of the suitability and risk of complications associated with device-specific therapies is also an important component of the preprocedural evaluation in this cohort. Although echocardiography including 2-dimensional and 3-dimensional methods has an important role in the initial assessment and procedural guidance, cross-sectional imaging, including both computed tomographic imagning and cardiac magnetic resonance imaging, is increasingly being integrated into the evaluation of mitral and tricuspid valve disease. In this review, we discuss the role of cross-sectional imaging in mitral and tricuspid valve disease, primarily valvular regurgitation assessment, with an emphasis on the preprocedural evaluation and implications for transcatheter interventions. © 2017 American Heart Association, Inc.

Sphingosine-1-phosphate receptor therapies: Advances in clinical trials for CNS-related diseases.

PubMed

O'Sullivan, Sinead; Dev, Kumlesh K

2017-02-01

The family of sphingosine-1-phosphate receptors (S1PRs) are G protein-coupled and comprise of five subtypes, S1P 1 -S1P 5 . These receptors are activated by the sphingolipid ligand, S1P, which is produced from the phosphorylation of sphingosine by sphingosine kinases. The activation of S1PRs modulates a host of cellular processes such as cell proliferation, migration and survival. These receptors are targeted by the drug fingolimod, a first in class oral therapy for multiple sclerosis. Importantly, S1PRs have also been implicated, in cellular experiments, pre-clinical studies and clinical trials in a range of other neurodegenerative diseases, neurological disorders and psychiatric illnesses, where S1PR drugs are proving beneficial. Overall, studies now highlight the importance of S1PRs as targets for modulating a variety of debilitating brain-related diseases. Here, we review the role of S1PRs in these illnesses. This article is part of the Special Issue entitled 'Lipid Sensing G Protein-Coupled Receptors in the CNS'. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical implications of drug abuse epidemiology.

PubMed

Schulden, Jeffrey D; Lopez, Marsha F; Compton, Wilson M

2012-06-01

Research on the epidemiology of illicit drug use disorders provides continued critical insights into the distribution and determinants of drug use and drug use disorders in the United States. This research serves as a foundation for understanding the etiology of these disorders, helping to disentangle the complex interrelationship of developmental, genetic, and environmental risk and protective factors. Building on an understanding of this research in substance abuse epidemiology, it is important for clinicians to understand the unique trends in drug use in the overall communities that they serve and the unique risk factors for given individuals. The generally high prevalence of substance use disorders, along with their high comorbidity with other psychiatric disorders and with the HIV epidemic, make prevention, evaluation, and referral for treatment for drug abuse an important part of routine clinical practice in a range of clinical settings, including primary care, psychiatric, and emergency department settings. Ongoing efforts to ensure insurance coverage parity for the treatment of mental health and substance use disorders offer the promise of continued improvements in the integration and availability of such services in the broader US health care system.

The Need to Objectively Measure Physical Activity During Pregnancy: Considerations for Clinical Research and Public Health Impact.

PubMed

Guérin, Eva; Ferraro, Zachary M; Adamo, Kristi B; Prud'homme, Denis

2018-05-01

Engaging in recommended levels of physical activity during pregnancy can provide a host of physical and mental health benefits for the expecting mother and her child. However, methodological issues related to physical activity measurement have plagued many studies examining the effects of physical activity during this important life stage. Burgeoning support exists for the more widespread use of objective methods, and accelerometers specifically, for an accurate appraisal of maternal physical activity. In this commentary, we highlight discrepancies between activity estimates obtained via self-report and objective measures and describe the implications of erroneous measurement when making clinical recommendations and in conducting future physical activity and pregnancy research. Most importantly, we aim to foster academic discussion and propose a call to action requiring a paradigm shift where we acknowledge the shortcomings of self-report and move toward an empirically driven approach for physical activity measurement. Results from more high-quality research studies will help support public health messaging and facilitate trust among health care providers, clinical researchers, and expecting mothers regarding the health benefits of physical activity recommendations.

Clinical characteristics and legal consequences of violent behavior: a case of bipolar disorder.

PubMed

Gómez-Durán, E L; Carrión, M I; Xifró, A; Martin-Fumadó, C

2010-01-01

The main subject of criminal proceedings is that of criminal responsibility, from this point of view bipolar disorders sometimes seem to be a neglected subject in legal scholarship. Yet they may affect decision-making across the spectrum of the law, especially when manic and psychotic symptoms are implicated. This case studies a 37-year-old woman, diagnosed with bipolar affective in disorder, who attacked the neighbour of her ex-husband during a manic episode with psychotic symptoms. Two groups of those psychotic symptoms are especially remarkable: delusions and experiences of influences playing on her body and thought insertion (threat/control–override symptoms). Hostility against her ex-husband was also implicated in the attack. Researchers have pointed all those symptoms as important predictors of violence, and they have determinant legal correlates.

Working models of attachment to parents and partners: implications for emotional behavior between partners.

PubMed

Mehta, Neera; Cowan, Philip A; Cowan, Carolyn P

2009-12-01

This study examined whether working models of attachment are associated with observed positive emotion, sadness, and anger during marital conflict. Individuals (n = 176) from a longitudinal study of families participated in the current cross-sectional study. Narrative interviews assessed the unique and combined contribution of attachment representations based on parents (adult attachment) and partner (couple attachment). The influence of partner's attachment, depression symptoms, and sex of participant was also examined. Hierarchical linear models demonstrated that one's couple attachment security predicts one's observed positive emotion, whereas the partner's couple attachment security predicts one's observed negative emotion. Partner's depression symptoms moderated the effects of partner's couple attachment. Adult attachment was not related to observed emotional behavior between partners. These findings have important clinical implications for individual, couple, and family therapy.

Existential isolation and I-sharing: Interpersonal and intergroup implications.

PubMed

Pinel, Elizabeth C

2018-01-11

I-sharing, or believing one has the same in-the-moment experience as another person, constitutes a specific way in which people may share reality. I-sharing research underscores its significance for interpersonal and intergroup outcomes. I-sharing fosters liking for people who differ from us in objective and sometimes important ways, and counteracts robust tendencies to favor ingroup members and dehumanize outgroup members. Research and theory indicate that existential isolation-feeling alone in one's experience-explains the potency of I-sharing, insofar as people with high levels of existential isolation are especially drawn to those with whom they have reason to believe they I-share. Recent findings are reviewed, followed by a discussion of the clinical implications of the work. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Towards integration of health economics into medical education and clinical practice in Saudi Arabia.

PubMed

Da'ar, Omar B; Al Shehri, Ali M

2015-04-01

In an era of expanding health sectors and rising costs, doctors are expected to have a working knowledge of health economics to better use resources and improve outcomes and quality of health care. This article recognizes the dearth of knowledge and application of economic analyses in medical education and clinical practice in Saudi Arabia. In particular, it highlights the desirability of knowledge of health economics in ensuring certain competencies in medical education and the rationale for inviting doctors to apply knowledge of economics in Saudi Arabia. In addition, the article discusses challenges that hinder integrating health economics into clinical practice. Furthermore, the article typifies some of the important economic phenomena that physicians need to discern. Besides, the article provides implications for incorporating economic analysis into medical education and clinical practice in Saudi Arabia. Finally, the article concludes by demonstrating how health economics can enhance doctors' knowledge and recommends the country to move towards integrating health economics into medical education and clinical practice for best practice.

[Implications in primary health care of medical genetics and genomic in type 2 diabetes mellitus].

PubMed

Ramirez-Garcia, Sergio Alberto; Cabrera-Pivaral, Carlos E; Huacuja-Ruiz, Luis; Flores-Alvarado, Luis Javier; Pérez-García, Guillermo; González-Rico, José Luis; López-Velázquez, Alma; Topete-González, Luz Rosalba; Rosales-Góme, Roberto Carlos; Candelario-Mejía, Gerardo; Villa-Ruano, Nemesio

2013-01-01

Type 2 diabetes mellitus is a complex disease and a global health problem. Therefore, the first level of health care should handle the approaches of medical genetics and genomics to reduce its incidence. The aim is to present perspectives analyzed by our group in two areas of genetics and its clinical application. Emphasis is placed on the coexistence of several genetic forms clinically detectable in patients with diabetes, missing heritability associated with low penetrance, and epigenomics mechanism. It is discussed the effect of genetic variation associated with resistance to insulin, beta-cell dysfunction, shaft incretin, and other points of interest, such as thrifty genotype hypothesis, conformational disease, genetically unknown foods, phenocopies as clinically silent hypercortisolism, molecular phytopharmacology in the clinical management. Finally, the result was displayed in the Mexican population from genetic studies and new findings of clinical importance, such as involvement of melatonin and effect of variations in the number of copies in a genomic region.

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.

Cirrhotic cardiomyopathy: Implications for the perioperative management of liver transplant patients

PubMed Central

Rahman, Suehana; Mallett, Susan V

2015-01-01

Cirrhotic cardiomyopathy is a disease that has only recently been recognised as a definitive clinical entity. In the setting of liver cirrhosis, it is characterized by a blunted inotropic and chronotropic response to stress, impaired diastolic relaxation of the myocardium and prolongation of the QT interval in the absence of other known cardiac disease. A key pathological feature is the persistent over-activation of the sympathetic nervous system in cirrhosis, which leads to down-regulation and dysfunction of the β-adrenergic receptor. Diagnosis can be made using a combination of echocardiography (resting and stress), tissue Doppler imaging, cardiac magnetic resonance imaging, 12-lead electrocardiogram and measurement of biomarkers. There are significant implications of cirrhotic cardiomyopathy in a number of clinical situations in which there is an increased physiological demand, which can lead to acute cardiac decompensation and heart failure. Prior to transplantation there is an increased risk of hepatorenal syndrome, cardiac failure following transjugular intrahepatic portosystemic shunt insertion and increased risk of arrhythmias during acute gastrointestinal bleeding. Liver transplantation presents the greatest physiological challenge with a further risk of acute cardiac decompensation. Peri-operative management should involve appropriate choice of graft and minimization of large fluctuations in preload and afterload. The avoidance of cardiac failure during this period has important prognostic implications, as there is evidence to suggest a long-term resolution of the abnormalities in cirrhotic cardiomyopathy. PMID:25848474

The importance of building trust and tailoring interactions when meeting older adults' health literacy needs.

PubMed

Brooks, Charlotte; Ballinger, Claire; Nutbeam, Don; Adams, Jo

2017-11-01

Health literacy is the ability to access, understand and use health information. This study qualitatively explored the views and experiences of older adults with varying health literacy levels who had attended a falls clinic on their overall experience of the falls clinic, access to the service and provider-patient interaction. Individual semi-structured interviews were conducted with nine older adults using a falls clinic in England. Health literacy was assessed using the REALM and NVS-UK. Interviews were audio-recorded, transcribed verbatim and interrogated using interpretative phenomenological analysis (IPA). Two superordinate themes emerged from the analysis: The importance of trust and relationship building to achieve effective communication with older adults; and the importance of tailoring education and healthcare to older adults' individual health literacy needs and preferences. The findings corroborate previous research emphasising the importance of face-to-face communication in responding to older adults' individual health literacy needs. Building trust in the relationship and tailoring communication to older adults' individual attributes and preferred learning styles is essential. Healthcare practitioners and managers should consider how service organisation and communication methods can enhance positive and effective relationships with patients. Improved training could support healthcare providers in meeting patients' personal communication needs. Implications for Rehabilitation Rehabilitation professionals should be aware of their patients' individual health literacy needs and communication/learning preferences. It is important to build relationships and trust with older adults attending rehabilitation services. Further training for rehabilitation professionals could support them in meeting patients' personal communication needs.

The roles of deliberate practice and innate ability in developing expertise: evidence and implications.

PubMed

Kulasegaram, Kulamakan M; Grierson, Lawrence E M; Norman, Geoffrey R

2013-10-01

Medical education research focuses extensively on experience and deliberate practice (DP) as key factors in the development of expert performance. The research on DP minimises the role of individual ability in expert performance. This claim ignores a large body of research supporting the importance of innate individual cognitive differences. We review the relationship between DP and an innate individual ability, working memory (WM) capacity, to illustrate how both DP and individual ability predict expert performance. This narrative review examines the relationship between DP and WM in accounting for expert performance. Studies examining DP, WM and individual differences were identified through a targeted search. Although all studies support extensive DP as a factor in explaining expertise, much research suggests individual cognitive differences, such as WM capacity, predict expert performance after controlling for DP. The extent to which this occurs may be influenced by the nature of the task under study and the cognitive processes used by experts. The importance of WM capacity is greater for tasks that are non-routine or functionally complex. Clinical reasoning displays evidence of this task-dependent importance of individual ability. No single factor is both necessary and sufficient in explaining expertise, and individual abilities such as WM can be important. These individual abilities are likely to contribute to expert performance in clinical settings. Medical education research and practice should identify the individual differences in novices and experts that are important to clinical performance. © 2013 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.

Novel hypothesis to explain why SGLT2 inhibitors inhibit only 30-50% of filtered glucose load in humans.

PubMed

Abdul-Ghani, Muhammad A; DeFronzo, Ralph A; Norton, Luke

2013-10-01

Inhibitors of sodium-glucose cotransporter 2 (SGLT2) are a novel class of antidiabetes drugs, and members of this class are under various stages of clinical development for the management of type 2 diabetes mellitus (T2DM). It is widely accepted that SGLT2 is responsible for >80% of the reabsorption of the renal filtered glucose load. However, maximal doses of SGLT2 inhibitors fail to inhibit >50% of the filtered glucose load. Because the clinical efficacy of this group of drugs is entirely dependent on the amount of glucosuria produced, it is important to understand why SGLT2 inhibitors inhibit <50% of the filtered glucose load. In this Perspective, we provide a novel hypothesis that explains this apparent puzzle and discuss some of the clinical implications inherent in this hypothesis.

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

Advances in Aβ plaque detection and the value of knowing: overcoming challenges to improving patient outcomes in Alzheimer's disease.

PubMed

Jovalekic, Aleksandar; Bullich, Santiago; Catafau, Ana; de Santi, Susan

2016-12-01

Clinical diagnosis of Alzheimer's disease (AD) can be challenging as numerous diseases mimic the characteristics of AD. In this light, recent guidelines developed by different associations and working groups point out the need for biomarkers to support AD diagnosis. This paper discusses 18F-labeled radiotracers (which are indicated for PET imaging of the brain) and ongoing clinical studies that aim to generate new evidence for the usage of amyloid imaging. In addition to their relatively long half-life, these agents are known for their high sensitivity and high negative predictive values for detection of neuritic Aβ plaques. Comparisons with other biomarkers are provided and implications of diagnostic disclosures discussed. Finally, recent data from clinical trials underscore the importance of amyloid PET for detecting, quantifying and monitoring Aβ plaque deposits.

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.

Managed care. What is its impact on nursing education and practice?

PubMed

Malloy, C

1997-08-01

Market forces present the nursing profession with an urgency to prepare gerontological nurses to assume significant roles in the managed care industry. An understanding of the current managed care environment underscores the need for training. Nurses require a "managed care" skill-set encompassing a firm grasp of the organization, financing, delivery, and policy implications of managed care as well as advanced practice clinical skills and a sound business orientation. The importance of the consumer as a significant player in managed care is highlighted.

Challenges in pulmonary fibrosis · 3: Cystic lung disease

PubMed Central

Cosgrove, Gregory P; Frankel, Stephen K; Brown, Kevin K

2007-01-01

Cystic lung disease is a frequently encountered problem caused by a diverse group of diseases. Distinguishing true cystic lung disease from other entities, such as cavitary lung disease and emphysema, is important given the differing prognostic implications. In this paper the features of the cystic lung diseases are reviewed and contrasted with their mimics, and the clinical and radiographic features of both diffuse (pulmonary Langerhans' cell histiocytosis and lymphangioleiomyomatosis) and focal or multifocal cystic lung disease are discussed. PMID:17726170

Incorporating Dispositional Traits into the Treatment of Anorexia Nervosa

PubMed Central

Herzog, David; Moskovich, Ashley; Merwin, Rhonda; Lin, Tammy

2014-01-01

We provide a general framework to guide the development of interventions that aim to address persistent features in eating disorders that may preclude effective treatment. Using perfectionism as an exemplar, we draw from research in cognitive neuroscience regarding attention and reinforcement learning, from learning theory and social psychology regarding vicarious learning and implications for the role modeling of significant others, and from clinical psychology on the importance of verbal narratives as barriers that may influence expectations and shape reinforcement schedules. PMID:21243482

Multidrug Efflux Systems in Microaerobic and Anaerobic Bacteria

PubMed Central

Xu, Zeling; Yan, Aixin

2015-01-01

Active drug efflux constitutes an important mechanism of antibiotic and multidrug resistance in bacteria. Understanding the distribution, expression, and physiological functions of multidrug efflux pumps, especially under physiologically and clinically relevant conditions of the pathogens, is the key to combat drug resistance. In animal hosts, most wounded, infected and inflamed tissues display low oxygen tensions. In this article, we summarize research development on multidrug efflux pumps in the medicinally relevant microaerobic and anaerobic pathogens and their implications in the effort to combat drug-resistant infections. PMID:27025630

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

Social networking between cells of the foetal skeleton: the importance of thyroid hormones.

PubMed

Farquharson, Colin

2011-08-01

In this issue of Journal of Endocrinology, Lanham et al. investigated the effects of hypothyroidism on the developing skeleton of the ovine foetus in utero. Their analyses indicated that, following thyroidectomy, bone growth, structure and mechanical properties were all altered at late gestation or at term. Adrenalectomy, whilst preventing the prepartum rise in triiodothyronine, did not modify skeletal development. The hypothyroid-mediated skeletal defects of the developing foetus described in this study may have clinical implications for bone health in later life.

Modulating kidney transplant interstitial fibrosis and tubular atrophy: is the RAAS an important target?

PubMed

Amer, Hatem; Griffin, Matthew D

2014-02-01

In follow-up to a recently published randomized controlled clinical trial, Issa et al. provide evidence that systemic activity and physiological responsiveness of the renin aldosterone angiotensin system (RAAS) are well within normal limits in most kidney recipients during the first 5 years post-transplant. Implications of the results include the need to better understand intra-renal RAAS activity in transplanted kidneys and to identify patients in which the graft-protective effects of RAAS blockade are most relevant.

A descriptive correlational study of bacterial vaginosis in pregnancy and its association with preterm birth: implications for advanced practice nurses.

PubMed

Mascagni, Jennifer R; Miller, Lucy H

2004-12-01

To expand on prior (often contradictory) research implicating maternal infection as a cause of preterm birth, specifically exploring whether bacterial vaginosis (BV) in pregnancy caused preterm birth in a sample of 103 women in a rural Mississippi obstetric-gynecologic clinic. This descriptive correlational study explored the relationship between BV and preterm birth, using retrospective chart data from a purposive sample of 103 women (for a power level of 95%) from one rural obstetric-gynecologic clinic. Contrary to the majority of published research, this study did not find a positive correlation between BV and preterm birth. This unexpected result raises questions, particularly given that the preponderance (86%) of women who tested positive for BV during their pregnancy were African American, a population in which both BV and preterm birth are more prevalent. Whether to screen for BV in pregnancy is a clinically important question not only in terms of the health of mother and child but also in terms of responsible use of resources. Clear findings supporting beneficial health results for screening would dictate screening regardless of the cost. But research continues to lack consensus on the efficacy of BV screening during pregnancy in preventing adverse pregnancy outcomes. In this study, as in some of the literature, the risk of preterm birth did not correlate positively with BV during pregnancy. In the absence of that correlation, cost gains importance. Nurse practitioners (NPs) must use resources wisely, including time, laboratory tests, and medications. Although some specialists recommend screening or treating all pregnant patients for BV, the current practice of not screening or treating all pregnant patients seems warranted until definitive findings establish a conclusive correlation between BV and preterm birth.

The crisis in United States hospital emergency services.

PubMed

Harrison, Jeffrey P; Ferguson, Emily D

2011-01-01

Emergency services are critical for high-quality healthcare service provision to support acute illness, trauma and disaster response. The greater availability of emergency services decreases waiting time, improves clinical outcomes and enhances local community well being. This study aims to assess United States (U.S.) acute care hospital staffs ability to provide emergency medical services by evaluating the number of emergency departments and trauma centers. Data were obtained from the 2003 and 2007 American Hospital Association (AHA) annual surveys, which included over 5000 US hospitals and provided extensive information on their infrastructure and healthcare capabilities. U.S. acute care hospital numbers decreased by 59 or 1.1 percent from 2003 to 2007. Similarly, U.S. emergency rooms and trauma centers declined by 125, or 3 percent. The results indicate that US hospital staffs ability to respond to traumatic injury and disasters has declined. Therefore, US hospital managers need to increase their investment in emergency department beds as well as provide state-of-the-art clinical technology to improve emergency service quality. These investments, when linked to other clinical information systems and the electronic medical record, support further healthcare quality improvement. This research uses the AHA annual surveys,which represent self-reported data by individual hospital staff. However, the AHA expendssignificant resources to validate reported information and the annual survey data are widely used for hospital research. The declining US emergency rooms and trauma centers have negative implications for patients needing emergency services. More importantly, this research has significant policy implications because it documents a decline in the US emergency healthcare service infrastructure. This article has important information on US emergency service availability in the hospital industry.

Agreement between electronic medical record-based and self-administered pain numeric rating scale: clinical and research implications.

PubMed

Goulet, Joseph L; Brandt, Cynthia; Crystal, Stephen; Fiellin, David A; Gibert, Cynthia; Gordon, Adam J; Kerns, Robert D; Maisto, Stephen; Justice, Amy C

2013-03-01

Pain screening may improve the quality of care by identifying patients in need of further assessment and management. Many health care systems use the numeric rating scale (NRS) for pain screening, and record the score in the patients' electronic medical record (EMR). Determine the level of agreement between EMR and patient survey NRS, and whether discrepancies vary by demographic and clinical characteristics. We linked survey data from a sample of veterans receiving care in 8 Veterans Affairs medical facilities, to EMR data including an NRS collected on the day of the survey to compare responses to the NRS question from these 2 sources. We assessed correlation, agreement on clinical cut-points (eg, severe), and, using the survey as the gold standard, whether patient characteristics were associated with a discrepancy on moderate-severe pain. A total of 1643 participants had a survey and EMR NRS score on the same day. The correlation was 0.56 (95% confidence interval, 0.52-0.59), but the mean EMR score was significantly lower than the survey score (1.72 vs. 2.79; P<0.0001). Agreement was moderate (κ=0.35). Characteristics associated with an increased odds of a discrepancy included: diabetes [adjusted odds ratio (AOR)=1.48], posttraumatic stress disorder (AOR=1.59), major depressive disorder (AOR=1.81), other race versus white (AOR=2.29), and facility in which care was received. The underestimation of pain using EMR data, especially clinically actionable levels of pain, has important clinical and research implications. Improving the quality of pain care may require better screening.

Ethical and social implications of genetic testing for communication disorders.

PubMed

Arnos, Kathleen S

2008-01-01

Advances in genetics and genomics have quickly led to clinical applications to human health which have far-reaching consequences at the individual and societal levels. These new technologies have allowed a better understanding of the genetic factors involved in a wide range of disorders. During the past decade, incredible progress has been made in the identification of genes involved in the normal process of hearing. The resulting clinical applications have presented consumers with new information and choices. Many of the same gene identification techniques are increasingly being applied to the investigation of complex disorders of speech and language. In parallel with gene identification, studies of the legal, ethical and psychosocial impacts of the clinical application of these advances and their influence on specific behaviors of individuals with communication disorders are paramount, but often lag behind. These studies will help to ensure that new technologies are introduced into clinical practice in a responsible manner. As a result of this activity, the participant will be able to (1) explain the differences between Mendelian and complex forms of inheritance and why these differences complicate the ethical impact of genetic testing, (2) explain how publicly funded genome research through the Human Genome Project, the International HapMap Project and others have examined the ethical, legal and social implications of genome research, (3) list some of the ethical complexities of prenatal, newborn and predictive testing for various genetic disorders and (4) discuss the importance of evidence-based practice to the development of public policy for the introduction and clinical use of genetic tests.

Professional Identity Formation and the Clinician-Scientist: A Paradigm for a Clinical Career Combining Two Distinct Disciplines.

PubMed

Rosenblum, Norman D; Kluijtmans, Manon; Ten Cate, Olle

2016-12-01

The clinician-scientist role is critical to the future of health care, and in 2010, the Carnegie Report on Educating Physicians focused attention on the professional identity of practicing clinicians. Although limited in number, published studies on the topic suggest that professional identity is likely a critical factor that determines career sustainability. In contrast to clinicians with a singular focus on clinical practice, clinician-scientists combine two major disciplines, clinical medicine and scientific research, to bridge discovery and clinical care. Despite its importance to advancing medical practice, the clinician-scientist career faced a variety of threats, which have been identified recently by the 2014 National Institutes of Health Physician Scientist Workforce. Yet, professional identity development in this career pathway is poorly understood. This Perspective focuses on the challenges to the clinician-scientist's professional identity and its development. First, the authors identify the particular challenges that arise from the different cultures of clinical care and science and the implications for clinician-scientist professional identity formation. Next, the authors synthesize insights about professional identity development within a dual-discipline career and apply their analysis to a discussion about the implications for clinician-scientist identity formation. Although not purposely developed to address identity formation, the authors highlight those elements within clinician-scientist training and career development programs that may implicitly support identity development. Finally, the authors highlight a need to identify empirically the elements that compose and determine clinician-scientist professional identity and the processes that shape its formation and sustainability.

Ethical and social implications of genetic testing for communication disorders

PubMed Central

Arnos, Kathleen S.

2013-01-01

Advances in genetics and genomics have quickly led to clinical applications to human health which have far-reaching consequences at the individual and societal levels. These new technologies have allowed a better understanding of the genetic factors involved in a wide range of disorders. During the past decade, incredible progress has been made in the identification of genes involved in the normal process of hearing. The resulting clinical applications have presented consumers with new information and choices. Many of the same gene identification techniques are increasingly being applied to the investigation of complex disorders of speech and language. In parallel with gene identification, studies of the legal, ethical and psychosocial impacts of the clinical application of these advances and their influence on specific behaviors of individuals with communication disorders are paramount, but often lag behind. These studies will help to ensure that new technologies are introduced into clinical practice in a responsible manner. Learning outcomes As a result of this activity, the participant will be able to (1) explain the differences between Mendelian and complex forms of inheritance and why these differences complicate the ethical impact of genetic testing, (2) explain how publicly funded genome research through the Human Genome Project, the International HapMap Project and others have examined the ethical, legal and social implications of genome research, (3) list some of the ethical complexities of prenatal, newborn and predictive testing for various genetic disorders and (4) discuss the importance of evidence-based practice to the development of public policy for the introduction and clinical use of genetic tests. PMID:18452941

Implications of Placebo and Nocebo Effects for Clinical Practice: Expert Consensus.

PubMed

Evers, Andrea W M; Colloca, Luana; Blease, Charlotte; Annoni, Marco; Atlas, Lauren Y; Benedetti, Fabrizio; Bingel, Ulrike; Büchel, Christian; Carvalho, Claudia; Colagiuri, Ben; Crum, Alia J; Enck, Paul; Gaab, Jens; Geers, Andrew L; Howick, Jeremy; Jensen, Karin B; Kirsch, Irving; Meissner, Karin; Napadow, Vitaly; Peerdeman, Kaya J; Raz, Amir; Rief, Winfried; Vase, Lene; Wager, Tor D; Wampold, Bruce E; Weimer, Katja; Wiech, Katja; Kaptchuk, Ted J; Klinger, Regine; Kelley, John M

2018-06-12

Placebo and nocebo effects occur in clinical or laboratory medical contexts after administration of an inert treatment or as part of active treatments and are due to psychobiological mechanisms such as expectancies of the patient. Placebo and nocebo studies have evolved from predominantly methodological research into a far-reaching interdisciplinary field that is unravelling the neurobiological, behavioural and clinical underpinnings of these phenomena in a broad variety of medical conditions. As a consequence, there is an increasing demand from health professionals to develop expert recommendations about evidence-based and ethical use of placebo and nocebo effects for clinical practice. A survey and interdisciplinary expert meeting by invitation was organized as part of the 1st Society for Interdisciplinary Placebo Studies (SIPS) conference in 2017. Twenty-nine internationally recognized placebo researchers participated. There was consensus that maximizing placebo effects and minimizing nocebo effects should lead to better treatment outcomes with fewer side effects. Experts particularly agreed on the importance of informing patients about placebo and nocebo effects and training health professionals in patient-clinician communication to maximize placebo and minimize nocebo effects. The current paper forms a first step towards developing evidence-based and ethical recommendations about the implications of placebo and nocebo research for medical practice, based on the current state of evidence and the consensus of experts. Future research might focus on how to implement these recommendations, including how to optimize conditions for educating patients about placebo and nocebo effects and providing training for the implementation in clinical practice. © 2018 S. Karger AG, Basel.

Modelling the resource implications and budget impact of new reimbursement guidelines for the management of cow milk allergy in Finland.

PubMed

Guest, Julian F; Valovirta, Erkka

2008-04-01

To assess the impact of the decision by Kela (The Social Insurance Institution) to adopt guidelines for the management of food allergies in children, developed by the Finnish Medical Society Duodecim, as the basis for reimbursing clinical nutrition preparations for the treatment of cow milk allergy (CMA) in Finland. A decision model was constructed using published clinical outcomes and clinician-derived resource utilisation estimates. The model was used to estimate the net resource implications and associated costs of Kela's new policy for the annual cohort of 1443 new CMA sufferers over the first 6 months following referral to a specialist. The analysis was conducted from the perspective of Kela, patients and Finnish society. Kela's new policy for reimbursing clinical nutrition preparations for the treatment of CMA is expected to increase healthcare resource use, including a 10% increase in the number of specialist visits over the first 6 months following referral. Consequently, Kela's 6-monthly expenditure on 1443 new CMA sufferers following referral is expected to increase by 12% from 889,389 euros to 992,761 euros. Additionally, parents' costs are expected to increase by 10% and fathers' absenteeism from work to increase by 11% within the first 6 months following referral. It is important to validate guidelines in clinical practice before their implementation. Within the limitations of our model, Kela's new criteria for reimbursing clinical nutrition preparations for the treatment of CMA is expected to increase healthcare resource use in paediatric departments in public hospitals in Finland and increase costs to Kela, patients and Finnish society.

Clinical implications of mutation analysis in primary hyperoxaluria type 1.

PubMed

van Woerden, Christiaan S; Groothoff, Jaap W; Wijburg, Frits A; Annink, Carla; Wanders, Ronald J A; Waterham, Hans R

2004-08-01

Primary hyperoxaluria type 1 (PH1) is an inborn error of glyoxylate metabolism with an extensive clinical and genetic heterogeneity. Although over 50 disease-causing mutations have been identified, the relationship between genotype and clinical outcome remains unclear. The aim of this study was to determine this association in order to find clues for improvement of patient care. AGXT mutation analysis and assessment of biochemical characteristics and clinical outcome were performed on patients from a Dutch PH1 cohort. Thirty-three of a cohort of 57 PH1 patients, identified in The Netherlands over a period of 30 years, were analyzed. Ten different mutations were found. The most common mutations were the Gly170Arg, Phe152Ile, and the 33insC mutations, with an allele frequency of 43%, 19%, and 15%, respectively. Homozygous Gly170Arg and Phe152Ile mutations were associated with pyridoxine responsiveness and a preserved renal function over time when treatment was timely initiated. All patients homozygous for the 33insC mutation had end-stage renal disease (ESRD) before the first year of age. In two unrelated patients, a new Val336Asp mutation was found coupled with the Gly170Arg mutation on the minor allele. We also found 3 patients homozygous for a novel Gly82Arg mutation with adverse outcome in 2 of them. Early detection of Gly170Arg and Phe152Ile mutations in PH1 has important clinical implications because of their association with pyridoxine responsiveness and clinical outcome. The association of a homozygous 33insC mutation with severe infantile ESRD, resulting in early deaths in 2 out of 3 cases, warrants a choice for prenatal diagnostics in affected families.

Treatment Paradigms for Advanced Non‐Small Cell Lung Cancer at Academic Medical Centers: Involvement in Clinical Trial Endpoint Design

PubMed Central

Borghaei, Hossein

2017-01-01

Abstract Based on the positive results of various clinical trials, treatment options for non‐small cell lung cancer (NSCLC) have expanded greatly over the last 25 years. While regulatory approvals of chemotherapeutic agents for NSCLC have largely been based on improvements in overall survival, recent approvals of many targeted agents for NSCLC (afatinib, crizotinib, ceritinib, osimertinib) have been based on surrogate endpoints such as progression‐free survival and objective response. As such, selection of appropriate clinical endpoints for examining the efficacy of investigational agents for NSCLC is of vital importance in clinical trial design. This review provides an overview of clinical trial endpoints previously utilized for approved agents for NSCLC and highlights the key efficacy results for these trials. Trends for more recent approvals in NSCLC, including those for the immunotherapeutic agents nivolumab and pembrolizumab, are also discussed. The results of a correlative analysis of endpoints from 18 clinical trials that supported approvals of investigational agents in clinical trials for NSCLC are also presented. Implications for Practice. While improving survival remains the ultimate goal of oncology clinical trials, overall survival may not always be the most feasible or appropriate endpoint to assess patient response. Recently, several investigational agents, both targeted agents and immunotherapies, have gained U.S. Food and Drug Administration approval in non‐small cell lung cancer based on alternate endpoints such as progression‐free survival or response rate. An understanding of the assessment of response and trial endpoint choice is important for future oncology clinical trial design. PMID:28408617

Preserving professional credibility: grounded theory study of medical trainees' requests for clinical support.

PubMed

Kennedy, Tara J T; Regehr, Glenn; Baker, G Ross; Lingard, Lorelei

2009-02-09

To develop a conceptual framework of the influences on medical trainees' decisions regarding requests for clinical support from a supervisor. Phase 1: members of teaching teams in internal and emergency medicine were observed during regular clinical activities (216 hours) and subsequently completed brief interviews. Phase 2: 36 in depth interviews were conducted using videotaped vignettes to probe tacit influences on decisions to request support. Data collection and analysis used grounded theory methods. Three teaching hospitals in an urban setting in Canada. 124 members of teaching teams on general internal medicine wards and in the emergency department, comprising 31 attending physicians, 57 junior and senior residents, 28 medical students, and eight nurses. Purposeful sampling to saturation was conducted. Trainees' decisions about whether or not to seek clinical support were influenced by three issues: the clinical question (clinical importance, scope of practice), supervisor factors (availability, approachability), and trainee factors (skill, desire for independence, evaluation). Trainees perceived that requesting frequent/inappropriate support threatened their credibility and used rhetorical strategies to preserve credibility. These strategies included building a case for the importance of requests, saving requests for opportune moments, making a plan before requesting support, and targeting requests to specific team members. Trainees consider not only clinical implications but also professional credibility when requesting support from clinical supervisors. Exposing the complexity of this process provides the opportunity to make changes to training programmes to promote timely supervision and provides a framework for further exploration of the impact of clinical training on quality of care of patients.

[Influence of Aging on Severity and Anti-Inflammatory Treatment of Experimental Dry Eye Disease].

PubMed

Steven, Philipp; Braun, Tobias; Krösser, Sonja; Gehlsen, Uta

2017-05-01

Purpose Aging is an important factor in dry-eye disease that has not been studied in the context of therapeutic measures. Aging-associated modifications of the ocular immune system implicate that anti-inflammatory therapies may act differently among younger individuals in terms of onset and effect of different substances. The goal of this study was to determine differences in clinical phenotype and topical anti-inflammatory therapy using a desiccating stress mouse model. Methods An experimental dry-eye disease (desiccating stress model) was induced in 12-week and 12-month-old female BALB/c mice. Topical therapy included 0.05% cyclosporine/F4H5 (Novaliq), F4H5, 0.05% cyclosporine (Restasis ® , Allergan) and dexamethasone (Monodex ® , Thea Pharma) for 3 consecutive weeks. A control group received no therapy whatsoever. Readout parameters included tear secretion, corneal fluorescein staining at 5 timepoints and histological analysis of goblet cell count at the end of the experiments. Results The older mice demonstrated a significantly stronger dry eye phenotype than the younger mice. Following therapy, the older mice responded to topical anti-inflammatory therapy significantly later than the younger individuals. Regarding the different substances used, cyclosporine/F4H5 showed a significantly faster decrease in corneal fluoresceine staining after only 1 week of therapy in comparison to all other groups. This substance was also superior regarding tear secretion and goblet cell count in age matched groups and in comparison to younger mice. Conclusions These experimental data support the implication that aging should be considered as an important factor in daily clinical practice. Furthermore, the differences found between substance classes, such as calcineurin antagonists and steroids, as well as different drug formulations, should be considered in future pre-clinical and clinical trials. Georg Thieme Verlag KG Stuttgart · New York.

Pharmaceutical Role Expansion and Developments in Pharmacist-Physician Communication.

PubMed

Bergman, Alicia A; Jaynes, Heather A; Gonzalvo, Jasmine D; Hudmon, Karen Suchanek; Frankel, Richard M; Kobylinski, Amanda L; Zillich, Alan J

2016-01-01

Expanded clinical pharmacist professional roles in the team-based patient-centered medical home (PCMH) primary care environment require cooperative and collaborative relationships among pharmacists and primary care physicians (PCPs), but many PCPs have not previously worked in such a direct fashion with pharmacists. Additional roles, including formulary control, add further elements of complexity to the clinical pharmacist-PCP relationship that are not well described. Our objective was to characterize the nature of clinical pharmacist-PCP interprofessional collaboration across seven federally funded hospitals and associated primary care clinics, following pharmacist placement in primary care clinics and incorporation of expanded pharmacist roles. In-depth and semistructured interviews were conducted with 25 practicing clinical pharmacists and 17 PCPs. Qualitative thematic analysis revealed three major themes: (1) the complexities of electronic communication (particularly electronic nonformulary requests) as contributing to interprofessional tensions or misunderstandings for both groups, (2) the navigation of new roles and traditional hierarchy, with pharmacists using indirect communication to prevent PCP defensiveness to recommendations, and (3) a preference for onsite colocation for enhanced communication and professional relationships. Clinical pharmacists' indirect communication practices may hold important implications for patient safety in the context of medication use, and it is important to foster effective communication skills and an environment where all team members across hierarchies can feel comfortable speaking up to reduce error when problems are suspected. Also, the lack of institutional communication about managing drug formulary issues and related electronic nonformulary request processes was apparent in this study and merits further attention for both researchers and practitioners.

The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes

PubMed Central

Pereira, Bernard; Chin, Suet-Feung; Rueda, Oscar M.; Vollan, Hans-Kristian Moen; Provenzano, Elena; Bardwell, Helen A.; Pugh, Michelle; Jones, Linda; Russell, Roslin; Sammut, Stephen-John; Tsui, Dana W. Y.; Liu, Bin; Dawson, Sarah-Jane; Abraham, Jean; Northen, Helen; Peden, John F.; Mukherjee, Abhik; Turashvili, Gulisa; Green, Andrew R.; McKinney, Steve; Oloumi, Arusha; Shah, Sohrab; Rosenfeld, Nitzan; Murphy, Leigh; Bentley, David R.; Ellis, Ian O.; Purushotham, Arnie; Pinder, Sarah E.; Børresen-Dale, Anne-Lise; Earl, Helena M.; Pharoah, Paul D.; Ross, Mark T.; Aparicio, Samuel; Caldas, Carlos

2016-01-01

The genomic landscape of breast cancer is complex, and inter- and intra-tumour heterogeneity are important challenges in treating the disease. In this study, we sequence 173 genes in 2,433 primary breast tumours that have copy number aberration (CNA), gene expression and long-term clinical follow-up data. We identify 40 mutation-driver (Mut-driver) genes, and determine associations between mutations, driver CNA profiles, clinical-pathological parameters and survival. We assess the clonal states of Mut-driver mutations, and estimate levels of intra-tumour heterogeneity using mutant-allele fractions. Associations between PIK3CA mutations and reduced survival are identified in three subgroups of ER-positive cancer (defined by amplification of 17q23, 11q13–14 or 8q24). High levels of intra-tumour heterogeneity are in general associated with a worse outcome, but highly aggressive tumours with 11q13–14 amplification have low levels of intra-tumour heterogeneity. These results emphasize the importance of genome-based stratification of breast cancer, and have important implications for designing therapeutic strategies. PMID:27161491

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.

What Are the Clinical Implications of New Onset or Worsening Anxiety During the First Two Weeks of SSRI Treatment for Depression?

PubMed Central

Gollan, Jackie K; Fava, Maurizio; Kurian, Benji; Wisniewski, Stephen R.; Rush, A. John; Daly, Ella; Miyahara, Sachiko; Trivedi, Madhukar H.

2013-01-01

Objective To evaluate the prevalence of new onset or worsening of anxiety symptoms, as well as their clinical implications, during the first two weeks of Selective Serotonin Reuptake Inhibitor (SSRI) pharmacotherapy for depression. Method Adult outpatients with non-psychotic major depressive disorder were enrolled in an 8-week acute phase SSRI treatment trial at 15 clinical sites across the US. Worsening anxiety was defined as a greater than 2 point increase on the Beck Anxiety Inventory (BAI) between baseline and Week 2. New onset of anxiety symptoms was ascribed when the BAI baseline rating was 0 and the Week 2 value was greater or equal to 2 points on the BAI. Results Overall, after two weeks of treatment, 48.8% (98 of 201 participants) reported improvement in anxiety symptoms, 36.3% (73 of 201) reported minimal symptom change, and 14.9% (30 of 201) reported worsening of anxiety symptoms. No association was found between change in anxiety symptoms within the first two weeks and change in depressive symptoms or remission at the end of 8 weeks of treatment. For participants with clinically meaningful anxiety symptoms at baseline, however, worsening of anxiety during the first two weeks of treatment was associated with worsening depressive symptoms by 8 weeks (p = .054). Conclusions The trajectory of anxiety symptom change early in SSRI treatment is an important indicator of eventual outcome for outpatients with major depression and baseline anxiety symptoms. PMID:22147631

Australian general practitioner attitudes to clinical practice guidelines and some implications for translating osteoarthritis care into practice.

PubMed

Basedow, Martin; Runciman, William B; Lipworth, Wendy; Esterman, Adrian

2016-11-01

Clinical practice guidelines (CPGs) have been shown to improve processes of care and health outcomes, but there is often a discrepancy between recommendations for care and clinical practice. This study sought to explore general practitioner (GP) attitudes towards CPGs, in general and specifically for osteoarthritis (OA), with the implications for translating OA care into practice. A self-administered questionnaire was conducted in January 2013 with a sample of 228 GPs in New South Wales and South Australia. Seventy-nine GPs returned questionnaires (response rate 35%). Nearly all GPs considered that CPGs support decision-making in practice (94%) and medical education (92%). Very few respondents regarded CPGs as a threat to clinical autonomy, and most recognised that individual patient circumstances must be taken into account. Shorter CPG formats were preferred over longer and more comprehensive formats, with preferences being evenly divided among respondents for short, 2-3-page summaries, flowcharts or algorithms and single page checklists. GPs considered accessibility to CPGs to be important, and electronic formats were popular. Familiarity and use of The Royal Australian College of General Practitioners OA Guideline was poor, with most respondents either not aware of it (30%; 95% confidence interval (CI) 27 - 41%), had never used it (19%; 95% CI 12 - 29%) or rarely used it (34%; 95% CI 25-45%). If CPGs are to assist with the translation of evidence into practice, they must be easily accessible and in a format that encourages use.

Critical Questions about PARADIGM-HF and the Future

PubMed Central

Chen, Chen-Huan

2016-01-01

Cardiovascular (CV) diseases in general and heart failure (HF) in particular are major contributors to death and morbidity and are also recognized as important drivers of health care expenditure. The PARADIGM-HF trial was a pivotal trial designed to compare the long-term effects of LCZ696 with enalapril in patients with symptomatic HF with reduced ejection fraction (HFrEF). This review article presents an in-depth view of the PARADIGM-HF trial and the implications of the results in the management of patients with HF and is based on peer reviewed manuscripts, editorials, perspectives and opinions written about the PARADIGM-HF trial. The article presents the key safety and efficacy results of the trial with specific emphasis on the clinical implications of these findings. The review highlights the highly statistically significant, 20% reduction in the primary composite endpoint of cardiovascular death or HF hospitalization, and a 16% reduction in the risk of death from any cause. It also provides an overview of the design, clinical findings, limitations and special areas of clinical interest. The review discusses the future of LCZ696 and additional trials that seek to answer questions in other sub-populations of patients with HF. The article reiterates what has been concluded by many experts in the field of HF- the introduction of LCZ696 into routine clinical care, while dependent on the regulatory approvals in various countries as well as acceptance by physicians, payers and patients, will change the treatment landscape for patients with HFrEF. PMID:27471351

Understanding what matters most to people with multiple myeloma: a qualitative study of views on quality of life

PubMed Central

2014-01-01

Background Multiple myeloma is an incurable haematological cancer that affects physical, psychological and social domains of quality of life (QOL). Treatment decisions are increasingly guided by QOL issues, creating a need to monitor QOL within clinical practice. The development of myeloma-specific QOL questionnaires has been limited by a paucity of research to fully characterise QOL in this group. Aims of the present study are to (1) explore the issues important to QOL from the perspective of people with multiple myeloma, and (2) explore the views of patients and clinical staff on existing QOL questionnaires and their use in clinical practice. Methods The ‘Issues Interviews’ were semi-structured qualitative interviews to explore the issues important to QOL in a purposive sample of myeloma patients (n = 20). The ‘Questionnaire Interviews’ were semi-structured qualitative interviews in a separate purposive sample of myeloma patients (n = 20) to explore views on existing QOL questionnaires and their clinical use. Two patient focus groups (n = 7, n = 4) and a focus group of clinical staff (n = 6) complemented the semi-structured interviews. Thematic content analysis resulted in the development of a theoretical model of QOL in myeloma. Results Main themes important to QOL were Biological Status, Treatment Factors, Symptoms Status, Activity & Participation, Emotional Status, Support Factors, Expectations, Adaptation & Coping and Spirituality. Symptoms had an indirect effect on QOL, only affecting overall QOL if they impacted upon Activity & Participation, Emotional Status or Support Factors. This indirect relationship has implications for the design of QOL questionnaires, which often focus on symptom status. Health-service factors emerged as important but are often absent from QOL questionnaires. Sexual function was important to patients and difficult for clinicians to discuss, so inclusion in clinical QOL tools may flag hidden problems and facilitate better care. Patients and staff expressed preferences for questionnaires to be no more than 2 pages long and to include a mixture of structured and open questions to focus the goals of care on what is most important to patients. Conclusion Existing QOL questionnaires developed and validated for use in myeloma do not capture all that is important to patients and may not be well suited to clinical use. PMID:25005145

Targeting the tyrosine kinase signalling pathways for treatment of immune-mediated glomerulonephritis: from bench to bedside and beyond

PubMed Central

Ma, Terry King-Wing; McAdoo, Stephen P.

2017-01-01

Glomerulonephritis (GN) affects patients of all ages and is an important cause of morbidity and mortality. Non-selective immunosuppressive drugs have been used in immune-mediated GN but often result in systemic side effects and occasionally fatal infective complications. There is increasing evidence from both preclinical and clinical studies that abnormal activation of receptor and non-receptor tyrosine kinase signalling pathways are implicated in the pathogenesis of immune-mediated GN. Activation of spleen tyrosine kinase (SYK), Bruton's tyrosine kinase (BTK), platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR) and discoidin domain receptor 1 (DDR1) have been demonstrated in anti-GBM disease. SYK is implicated in the pathogenesis of ANCA-associated GN. SYK, BTK, PDGFR, EFGR, DDR1 and Janus kinase are implicated in the pathogenesis of lupus nephritis. A representative animal model of IgA nephropathy (IgAN) is lacking. Based on the results from in vitro and human renal biopsy study results, a phase II clinical trial is ongoing to evaluate the efficacy and safety of fostamatinib (an oral SYK inhibitor) in high-risk IgAN patient. Various tyrosine kinase inhibitors (TKIs) have been approved for cancer treatment. Clinical trials of TKIs in GN may be justified given their long-term safety data. In this review we will discuss the current unmet medical needs in GN treatment and research as well as the current stage of development of TKIs in GN treatment and propose an accelerated translational research approach to investigate whether selective inhibition of tyrosine kinase provides a safer and more efficacious option for GN treatment. PMID:28391340

Targeting the tyrosine kinase signalling pathways for treatment of immune-mediated glomerulonephritis: from bench to bedside and beyond.

PubMed

Ma, Terry King-Wing; McAdoo, Stephen P; Tam, Frederick Wai Keung

2017-01-01

Glomerulonephritis (GN) affects patients of all ages and is an important cause of morbidity and mortality. Non-selective immunosuppressive drugs have been used in immune-mediated GN but often result in systemic side effects and occasionally fatal infective complications. There is increasing evidence from both preclinical and clinical studies that abnormal activation of receptor and non-receptor tyrosine kinase signalling pathways are implicated in the pathogenesis of immune-mediated GN. Activation of spleen tyrosine kinase (SYK), Bruton's tyrosine kinase (BTK), platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR) and discoidin domain receptor 1 (DDR1) have been demonstrated in anti-GBM disease. SYK is implicated in the pathogenesis of ANCA-associated GN. SYK, BTK, PDGFR, EFGR, DDR1 and Janus kinase are implicated in the pathogenesis of lupus nephritis. A representative animal model of IgA nephropathy (IgAN) is lacking. Based on the results from in vitro and human renal biopsy study results, a phase II clinical trial is ongoing to evaluate the efficacy and safety of fostamatinib (an oral SYK inhibitor) in high-risk IgAN patient. Various tyrosine kinase inhibitors (TKIs) have been approved for cancer treatment. Clinical trials of TKIs in GN may be justified given their long-term safety data. In this review we will discuss the current unmet medical needs in GN treatment and research as well as the current stage of development of TKIs in GN treatment and propose an accelerated translational research approach to investigate whether selective inhibition of tyrosine kinase provides a safer and more efficacious option for GN treatment. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA.

Interventions to support and develop clinician-researcher leadership in one health district.

PubMed

Fry, Margaret; Dombkins, Anthony

2017-07-10

Purpose Clinical leadership, researcher capacity and a culture of clinical inquiry are needed in the clinical workforce. The purpose of this paper is to report on a program which was used to develop and support clinicians to explore practice, implement innovation, translate evidence and build researcher capacity. Design/methodology/approach This pragmatic paper presents a case study of a nursing and midwifery clinician-researcher development program. The multi-site, multi-modal program focused on education, mentoring and support, communication networks, and clinician-university partnerships strategies to build workforce capacity and leadership. Findings Over 2,000 staff have been involved in the program representing a range of health disciplines. The study day program has been delivered to 500 participants with master classes having over 1,500 attendees. The research mentor program has demonstrated that participants increased their confidence for research leadership roles and are pursuing research and quality assurance projects. Communication strategies improved the visibility of nursing and midwifery. Research limitations/implications This case study was conducted in one health district, which may not have relevance to other geographical areas. The small numbers involved in the research mentor program need to be considered when reviewing the findings. Practical implications The program has been a catalyst for developing a research culture, clinical leadership and research networks that strengthen workforce capacity. Building researcher skills in the workforce will better support quality healthcare and the examination of everyday practice. Social implications Building a culture of healthcare that is based on inquiry and evidence-based practice will lead to more appropriate and consistent healthcare delivery. Consumers have the right to expect health clinicians will challenge everyday practice and have the skills and capability to translate or generate best evidence to underpin professional and service delivery. Originality/value This paper provides strategies for building workforce researcher capacity and capability. The program provides opportunity for building research networks and role modeling the value and importance of research to practice and quality improvement.

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

Clinical review: Distinguishing constitutional delay of growth and puberty from isolated hypogonadotropic hypogonadism: critical appraisal of available diagnostic tests.

PubMed

Harrington, Jennifer; Palmert, Mark R

2012-09-01

Determining the etiology of delayed puberty during initial evaluation can be challenging. Specifically, clinicians often cannot distinguish constitutional delay of growth and puberty (CDGP) from isolated hypogonadotropic hypogonadism (IHH), with definitive diagnosis of IHH awaiting lack of spontaneous puberty by age 18 yr. However, the ability to make a timely, correct diagnosis has important clinical implications. The aim was to describe and evaluate the literature regarding the ability of diagnostic tests to distinguish CDGP from IHH. A PubMed search was performed using key words "puberty, delayed" and "hypogonadotropic hypogonadism," and citations within retrieved articles were reviewed to identify studies that assessed the utility of basal and stimulation tests in the diagnosis of delayed puberty. Emphasis was given to a test's ability to distinguish prepubertal adolescents with CDGP from those with IHH. Basal gonadotropin and GnRH stimulation tests have limited diagnostic specificity, with overlap in gonadotropin levels between adolescents with CDGP and IHH. Stimulation tests using more potent GnRH agonists and/or human chorionic gonadotropin may have better discriminatory value, but small study size, lack of replication of diagnostic thresholds, and prolonged protocols limit clinical application. A single inhibin B level in two recent studies demonstrated good differentiation between groups. Distinguishing IHH from CDGP is an important clinical issue. Basal inhibin B may offer a simple, discriminatory test if results from recent studies are replicated. However, current literature does not allow for recommendation of any diagnostic test for routine clinical use, making this an important area for future investigation.

Visual mental imagery in psychopathology--implications for the maintenance and treatment of depression.

PubMed

Weßlau, Charlotte; Steil, Regina

2014-06-01

Negative mental images are a common feature in a range of mental disorders as well as in healthy subjects. Intrusive negative mental images have only recently become a focus of attention in clinical research on depression. Research so far indicates that they can be an important factor regarding the onset and chronicity of affective disorders. This article is the first to provide an extensive overview of the current state of research in the field of visual mental images in depression. It aims to investigate disorder-specific characteristics, as well as the role of imagery as a maintaining factor. A detailed definition and description of empirical results about mental images in depressive disorders is followed by a presentation and analysis of treatment studies using imagery techniques in depressed samples. Additionally, methodological issues like small sample sizes and the lack of control groups are pointed out and implications for future research are discussed. Case vignettes are included in the appendix to exemplify the importance of negative mental images in patients suffering from depression. Copyright © 2014 Elsevier Ltd. All rights reserved.

Revenge Pornography: Mental Health Implications and Related Legislation.

PubMed

Kamal, Mudasir; Newman, William J

2016-09-01

Revenge pornography, also known as nonconsensual pornography, is a subtype of cyberharassment/cyberstalking, and a serious problem facing society in the Internet age. Revenge pornography can result in lifelong mental health consequences for victims, damaged relationships, and social isolation. Recently, a growing number of states have recognized the importance of this phenomenon and have enacted legislation that criminalizes it. The technology industry has also taken steps to assist victims of revenge pornography by creating web forms to request removal of links leading to the explicit content. The Cyber Civil Rights Initiative (CCRI) has been instrumental in promoting public awareness of this often overlooked problem and in providing services for victims. Although important steps have been made, greater recognition of the gravity of this problem and the mental health implications of revenge pornography is needed to expand legislation criminalizing such acts. A federal criminal law, in particular, is much overdue. Mental health professionals must understand the dimensions of revenge pornography to be able to identify and address the consequences in both forensic and clinical settings. © 2016 American Academy of Psychiatry and the Law.

Conceptualization and Assessment of Disengagement in Romantic Relationships

PubMed Central

Barry, Robin A.; Lawrence, Erika; Langer, Amie

2008-01-01

Research examining relationship distress and dissolution highlights the importance of romantic disengagement. However, prior conceptualizations and measures of romantic disengagement have tended to combine disengagement with related but distinct constructs hindering the study of romantic disengagement. In the present study we conducted exploratory factor analyses to demonstrate that disengagement is a relatively distinct construct and to clarify the conceptualization of romantic disengagement. More importantly, we developed a novel measure– the Romantic Disengagement Scale (RDS). The RDS demonstrated adequate fit across samples of dating individuals, married couples and women in physically aggressive relationships. The RDS also demonstrated strong divergent and incremental validity. Implications for enhancing conceptual models, research methodology, and clinical interventions are discussed. PMID:19727315

Imaging Virus-Associated Cancer

PubMed Central

Fu, De-Xue; Foss, Catherine A.; Nimmagadda, Sridhar; Ambinder, Richard F.; Pomper, Martin G.

2012-01-01

Cancer remains an important and growing health problem. Researchers have made great progress in defining genetic and molecular alterations that contribute to cancer formation and progression. Molecular imaging can identify appropriate patients for targeted cancer therapy and may detect early biochemical changes in tumors during therapy, some of which may have important prognostic implications. Progress in this field continues largely due to a union between molecular genetics and advanced imaging technology. This review details uses of molecular-genetic imaging in the context of tumor-associated viruses. Under certain conditions, and particularly during pharmacologic stimulation, gammaherpesviruses will express genes that enable imaging and therapy in vivo. The techniques discussed are readily translatable to the clinic. PMID:18991718

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.

Personalizing medicine with clinical pharmacogenetics

PubMed Central

Scott, Stuart A.

2012-01-01

Clinical genetic testing has grown substantially over the past 30 years as the causative mutations for Mendelian diseases have been identified, particularly aided in part by the recent advances in molecular-based technologies. Importantly, the adoption of new tests and testing strategies (e.g., diagnostic confirmation, prenatal testing, and population-based carrier screening) has often been met with caution and careful consideration before clinical implementation, which facilitates the appropriate use of new genetic tests. Although the field of pharmacogenetics was established in the 1950s, clinical testing for constitutional pharmacogenetic variants implicated in interindividual drug response variability has only recently become available to help clinicians guide pharmacotherapy, in part due to US Food and Drug Administration-mediated product insert revisions that include pharmacogenetic information for selected drugs. However, despite pharmacogenetic associations with adverse outcomes, physician uptake of clinical pharmacogenetic testing has been slow. Compared with testing for Mendelian diseases, pharmacogenetic testing for certain indications can have a lower positive predictive value, which is one reason for underutilization. A number of other barriers remain with implementing clinical pharmacogenetics, including clinical utility, professional education, and regulatory and reimbursement issues, among others. This review presents some of the current opportunities and challenges with implementing clinical pharmacogenetic testing. PMID:22095251

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.

Microanalytic Assessment of Self-Regulated Learning During Clinical Reasoning Tasks: Recent Developments and Next Steps.

PubMed

Cleary, Timothy J; Durning, Steven J; Artino, Anthony R

2016-11-01

Helping medical educators obtain and use assessment data to assist medical students, residents, and physicians in reducing diagnostic errors and other forms of ineffective clinical practice is of critical importance. Self-Regulated Learning-Microanalytic Assessment and Training is an assessment-to-intervention framework designed to address this need by generating data about trainees' strategic processes (e.g., focusing on clinical task procedures), regulatory processes (e.g., planning how to do a task), and motivational processes (e.g., increasing confidence for performing a task) as they perform clinical activities. In this article, the authors review several studies that have used an innovative assessment approach, called self-regulated learning (SRL) microanalysis, to generate data about how trainees regulate their thinking and actions during clinical reasoning tasks. Across the studies, initial findings revealed that medical students often do not exhibit strategic thinking and action during clinical reasoning practice tasks even though some regulatory processes (e.g., planning) are predictive of important medical education outcomes. Further, trainees' motivation beliefs, strategic thinking, and self-evaluative judgments tend to shift rapidly during clinical skills practice and may also vary across different parts of a patient encounter. Collectively, these findings underscore the value of dynamically assessing trainees' SRL as they complete clinical tasks. The findings also set the stage for exploring how medical educators can best use SRL microanalytic assessment data to guide remedial practices and the provision of feedback to trainees. Implications and future research directions for connecting assessments to intervention in medical education are discussed.

Illness identity in young adults with refractory epilepsy.

PubMed

Luyckx, Koen; Oris, Leen; Raymaekers, Koen; Rassart, Jessica; Moons, Philip; Verdyck, Ludo; Mijnster, Teus; Mark, Ruth E

2018-03-01

Refractory epilepsy is an intrusive condition with important implications for daily functioning in emerging and young adulthood. The present study examined the degree to which refractory epilepsy is integrated in one's identity, and examined how such a sense of illness identity was related to health-related quality of life (HRQOL). A total of 121 18- to 40-year-old patients with refractory epilepsy (56.2% women) completed self-report questionnaires assessing the four illness identity states of acceptance, enrichment, engulfment, and rejection (Illness Identity Questionnaire (IIQ)); HRQOL (Quality of Life in Epilepsy Inventory - 31); and seizure frequency and severity (Liverpool Seizure Severity Scale (LSSS)). Illness identity scores were compared with a sample of 191 patients with a nonneurological chronic disease (congenital heart disease). Hierarchical regression analyses were conducted to assess the predictive value of illness identity for HRQOL when simultaneously controlling for demographic and clinical features. Patients with refractory epilepsy scored higher on rejection and engulfment and lower on acceptance when compared with patients with congenital heart disease. Further, seizure severity and number of medication side-effects were positively related to engulfment and negatively to acceptance. Finally, when simultaneously controlling for various demographic and clinical variables, illness identity significantly predicted HRQOL (with engulfment being the strongest and most consistent predictor). The extent to which patients with refractory epilepsy succeed in integrating their illness into their identity may have important implications for HRQOL. Clinicians should be especially attentive for signs that patients feel engulfed by their epilepsy. Copyright © 2018 Elsevier Inc. All rights reserved.

Nutrition and pharmacology: general principles and implications for HIV1234

PubMed Central

Raiten, Daniel J

2011-01-01

Food and nutrition play an intimate and inextricable role in all aspects of drug metabolism, safety, and effectiveness. Antiretroviral therapies (ART) have assumed a preeminent position in the prevention, care, and treatment of HIV and its comorbidities. The interaction between food, nutrition, and ART has become an expanding area of interest both in terms of clinical standards of care and as a target for research. Since the original review of this topic by the WHO in 2005, much has been learned (8). This article contains a review of what is known about the general relationships between nutrition and pharmacology, as well as issues specific to ART, with particular attention to their use in low- and middle-resource settings. The importance of food and nutrition on the bioavailability of drugs and vice versa has been an area of historical interest. However, much has been learned about the importance of nutritional status on drug metabolism, distribution, and effectiveness. The impact of traditional therapies (herbal/botanical) is highlighted as an area of clinical concern and one in need of further research. Additional attention is focused on the impact of individual micronutrients on drug pharmacokinetics and pharmacodynamics. Finally, attention is given to the nutritional implications of the metabolic consequences of ART, which include the potential impact of “colliding epidemics” of infection (eg, HIV, tuberculosis) and noncommunicable diseases. Much has been learned, but much remains to be accomplished to ensure the effective integration of nutritional considerations into the effective and safe use of ART. PMID:22089445

Correlates of quality of life among African American and white cancer survivors.

PubMed

Matthews, Alicia K; Tejeda, Silvia; Johnson, Timothy P; Berbaum, Michael L; Manfredi, Clara

2012-01-01

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. The objective of the study was to assess sociodemographic, clinical, and psychosocial factors associated with physical and mental health QOL (PHQOL and MHQOL) among African American and white cancer survivors. 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. Key racial differences in adjusted analyses included poorer MHQOL scores among African Americans compared with 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, being 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. Interventions aimed at increasing social support may have important implications for improving QOL outcomes among African Americans. Measuring and understanding factors associated with QOL have important implications for patient adjustment and clinical decision making.

Hypochondriasis Circumscripta: A Neglected Concept with Important Implications in Psychodermatology.

PubMed

Smulevich, Anatoly B; Lvov, Andrey N; Romanov, Dmitry V

2016-08-23

The article is devoted to a psychodermatological disorder with self-destructive behavior - hypochondriasis circumscripta. Presented data are based on a clinical analysis of 22 consecutive cases (15 female; mean age - 56.1 ± 12.6 years) observed in the dermatologic department of First Moscow State Medical University and managed in a multidisciplinary approach by dermatologists and a consultation-liaison psychiatrist. Psychopathology, clinical presentations, historical aspects and treatment options are discussed. The self-inflicted skin lesions result from a severe repetitive autodestruction of focal skin loci primarily affected with heterogeneous sensations associated with a hypochondrical over-valued idea. Hypochondriasis сircumscripta is a serious diagnostic and treatment challenge and should be distinguished from dermatitis artefacta, skin picking disorder and delusional infestation.

Data Sharing: A New Editorial Initiative of the International Committee of Medical Journal Editors. Implications for the Editors’ Network

PubMed Central

Alfonso, Fernando; Adamyan, Karlen; Artigou, Jean-Yves; Aschermann, Michael; Boehm, Michael; Buendia, Alfonso; Chu, Pao-Hsien; Cohen, Ariel; Dei Cas, Livio; Dilic, Mirza; Doubell, Anton; Echeverri, Dario; Enç, Nuray; Ferreira-González, Ignacio; J. Filipiak, Krzysztof; Flammer, Andreas; Fleck, Eckart; Gatzov, Plamen; Ginghina, Carmen; Goncalves, Lino; Haouala, Habib; Hassanein, Mahmoud; Heusch, Gerd; Huber, Kurt; Hulín, Ivan; Ivanusa, Mario; Krittayaphong, Rungroj; Lau, Chu-Pak; Marinskis, Germanas; Mach, François; Moreira, Luiz Felipe; Nieminen, Tuomo; Oukerraj, Latifa; Perings, Stefan; Pierard, Luc; Potpara, Tatjana; Reyes-Caorsi, Walter; Rim, Se-Joong; Rødevand, Olaf; Saade, Georges; Sander, Mikael; Shlyakhto, Evgeny; Timuralp, Bilgin; Tousoulis, Dimitris; Ural, Dilek; Piek, J. J.; Varga, Albert; Lüscher, Thomas F.

2017-01-01

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship- emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors’ Network of the European Society of Cardiology. PMID:28630534

A large left ventricular thrombus.

PubMed

Patanè, Salvatore; Marte, Filippo

2009-06-26

The discovery of a left ventricular mass obliges the clinician to perform a differential diagnosis including tumour or lipoma versus thrombus and its assessment presents important clinical implications. Dilated cardiomyopathy has been associated with left ventricular thrombosis which leads to substantial morbidity and mortality as a site for peripheral emboli. There are some studies on patients with dilated cardiomyopathy showing altered hemostasis and platelet behavior despite sinus rhythm. An increased incidence of thromboembolism is also well recognized in patients with left ventricular systolic dysfunction complicating history of myocardial infarction. Clinical dilemmas in treating left ventricular thrombus have been described too. We present a case of a large mobile left ventricular thrombus in a 71-year-old Italian man with dilated cardiomyopathy and history of myocardial infarction.

Furthering Our Understanding of Therapist Knowledge and Attitudinal Measurement in Youth Community Mental Health.

PubMed

Okamura, Kelsie H; Hee, Puanani J; Jackson, David; Nakamura, Brad J

2018-02-19

Examining therapist evidence-based practice (EBP) knowledge seems an important step for supporting successful implementation. Advances in implementation science suggest a distinction between practice specific (i.e., knowing which practices are derived from the evidence base) and EBP process (i.e., integrating research evidence, clinical experience, client characteristics, and monitoring outcomes) knowledge. An examination of how these knowledge types are measured and relate to attitudes appears warranted. In our sample of 58 youth community therapists, both practice specific and EBP process knowledge accounted for EBP attitude scores, which varied by therapist demographic variables. Implications for measurement of therapist constructs and future research in identifying therapist predictors of EBP use and youth clinical improvement are discussed.

Demystifying cognitive flexibility: Implications for clinical and developmental neuroscience

PubMed Central

Dajani, Dina R.; Uddin, Lucina Q.

2015-01-01

Cognitive flexibility, the readiness with which one can selectively switch between mental processes to generate appropriate behavioral responses, develops in a protracted manner and is compromised in several prevalent neurodevelopmental disorders. It is unclear whether cognitive flexibility arises from neural substrates distinct from the executive control network, or from the interplay of nodes within this and other networks. Here we review neuroimaging studies of cognitive flexibility, focusing on set shifting and task switching. We propose that more consistent operationalization and study of cognitive flexibility is required in clinical and developmental neuroscience. We suggest that an important avenue for future research is the characterization of the relationship between neural flexibility and cognitive flexibility in typical and atypical development. PMID:26343956

Jejunal Metastasis Colliding With a Borderline Tumor in the Ovary: A Hitherto Unreported Eventuality.

PubMed

Piana, Simonetta; Giunta, Alessandro; Valli, Riccardo

2015-10-01

Metastatic adenocarcinomas to the ovary can show morphologically innocuous areas simulating primary benign lesions or borderline tumors. Ruling out a metastasis can be a difficult issue for pathologists, especially when facing with cystic tumors. Because of the important clinical implications of differentiating metastatic adenocarcinomas from primary ovarian tumors, the integration of clinical, pathological, and immunohistochemical features is warranted, primarily in case of mucinous adenocarcinomas. Vice versa, the synchronous presence of a metastasis and a primary in the same ovary is virtually excluded as a very unlikely eventuality. Here, we describe a case of metastatic adenocarcinoma from the jejunum colliding with a seromucinous borderline tumor in the same ovary, an unreported eventuality so far. © The Author(s) 2015.

CMV and Immunosenescence: from basics to clinics

PubMed Central

2012-01-01

Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been suggested that it drives or at least exacerbates “immunosenescence”. This contention remains controversial and was the primary subject of the Third International Workshop on CMV & Immunosenescence which was held in Cordoba, Spain, 15-16th March, 2012. Discussions focused on several main themes including the effects of CMV on adaptive immunity and immunosenescence, characterization of CMV-specific T cells, impact of CMV infection and ageing on innate immunity, and finally, most important, the clinical implications of immunosenescence and CMV infection. Here we summarize the major findings of this workshop. PMID:23114110

[Clinical bioethics for primary health care].

PubMed

González-de Paz, L

2013-01-01

The clinical decision making process with ethical implications in the area of primary healthcare differs from other healthcare areas. From the ethical perspective it is important to include these issues in the decision making model. This dissertation explains the need for a process of bioethical deliberation for Primary Healthcare, as well as proposing a method for doing so. The decision process method, adapted to this healthcare area, is flexible and requires a more participative Healthcare System. This proposal involves professionals and the patient population equally, is intended to facilitate the acquisition of responsibility for personal and community health. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Evolving models of the immunopathogenesis of T-cell mediated drug allergy: the role of host, pathogens, and drug response

PubMed Central

White, Katie D.; Chung, Wen-Hung; Hung, Shuen-Iu; Mallal, Simon; Phillips, Elizabeth J.

2015-01-01

Immune-mediated adverse drug reactions (IM-ADRs) are an underrecognized source of preventable morbidity, mortality, and cost. Increasingly, genetic variation in the HLA loci is associated with risk of severe reactions, highlighting the importance of T-cell immune responses in the mechanisms of both B-cell mediated and primary T-cell mediated IM-ADRs. In this review, we summarize the role of host genetics, microbes and drugs in the development of IM-ADRs, expand upon the existing models of IM-ADR pathogenesis to address multiple unexplained observations, discuss the implications of this work in clinical practice today, and describe future applications for pre-clinical drug toxicity screening, drug design, and development. PMID:26254049

Intertumoral Heterogeneity within Medulloblastoma Subgroups.

PubMed

Cavalli, Florence M G; Remke, Marc; Rampasek, Ladislav; Peacock, John; Shih, David J H; Luu, Betty; Garzia, Livia; Torchia, Jonathon; Nor, Carolina; Morrissy, A Sorana; Agnihotri, Sameer; Thompson, Yuan Yao; Kuzan-Fischer, Claudia M; Farooq, Hamza; Isaev, Keren; Daniels, Craig; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Lee, Ji Yeoun; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Vasiljevic, Alexandre; Faure-Conter, Cecile; Jouvet, Anne; Giannini, Caterina; Nageswara Rao, Amulya A; Li, Kay Ka Wai; Ng, Ho-Keung; Eberhart, Charles G; Pollack, Ian F; Hamilton, Ronald L; Gillespie, G Yancey; Olson, James M; Leary, Sarah; Weiss, William A; Lach, Boleslaw; Chambless, Lola B; Thompson, Reid C; Cooper, Michael K; Vibhakar, Rajeev; Hauser, Peter; van Veelen, Marie-Lise C; Kros, Johan M; French, Pim J; Ra, Young Shin; Kumabe, Toshihiro; López-Aguilar, Enrique; Zitterbart, Karel; Sterba, Jaroslav; Finocchiaro, Gaetano; Massimino, Maura; Van Meir, Erwin G; Osuka, Satoru; Shofuda, Tomoko; Klekner, Almos; Zollo, Massimo; Leonard, Jeffrey R; Rubin, Joshua B; Jabado, Nada; Albrecht, Steffen; Mora, Jaume; Van Meter, Timothy E; Jung, Shin; Moore, Andrew S; Hallahan, Andrew R; Chan, Jennifer A; Tirapelli, Daniela P C; Carlotti, Carlos G; Fouladi, Maryam; Pimentel, José; Faria, Claudia C; Saad, Ali G; Massimi, Luca; Liau, Linda M; Wheeler, Helen; Nakamura, Hideo; Elbabaa, Samer K; Perezpeña-Diazconti, Mario; Chico Ponce de León, Fernando; Robinson, Shenandoah; Zapotocky, Michal; Lassaletta, Alvaro; Huang, Annie; Hawkins, Cynthia E; Tabori, Uri; Bouffet, Eric; Bartels, Ute; Dirks, Peter B; Rutka, James T; Bader, Gary D; Reimand, Jüri; Goldenberg, Anna; Ramaswamy, Vijay; Taylor, Michael D

2017-06-12

While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials. Copyright © 2017 Elsevier Inc. All rights reserved.

Hemoglobin Variants: Biochemical Properties and Clinical Correlates

PubMed Central

Thom, Christopher S.; Dickson, Claire F.; Gell, David A.; Weiss, Mitchell J.

2013-01-01

Diseases affecting hemoglobin synthesis and function are extremely common worldwide. More than 1000 naturally occurring human hemoglobin variants with single amino acid substitutions throughout the molecule have been discovered, mainly through their clinical and/or laboratory manifestations. These variants alter hemoglobin structure and biochemical properties with physiological effects ranging from insignificant to severe. Studies of these mutations in patients and in the laboratory have produced a wealth of information on hemoglobin biochemistry and biology with significant implications for hematology practice. More generally, landmark studies of hemoglobin performed over the past 60 years have established important paradigms for the disciplines of structural biology, genetics, biochemistry, and medicine. Here we review the major classes of hemoglobin variants, emphasizing general concepts and illustrative examples. PMID:23388674

Data Sharing: A New Editorial Initiative of the International Committee of Medical Journal Editors. Implications for the Editors´ Network.

PubMed

Alfonso, Fernando; Adamyan, Karlen; Artigou, Jean Yves; Aschermann, Michael; Boehm, Michael; Buendia, Alfonso; Chu, Pao Hsien; Cohen, Ariel; Cas, Livio Dei; Dilic, Mirza; Doubell, Anton; Echeverri, Dario; Enç, Nuray; Ferreira-González, Ignacio; Filipiak, Krzysztof J; Flammer, Andreas; Fleck, Eckart; Gatzov, Plamen; Ginghina, Carmen; Goncalves, Lino; Haouala, Habib; Hassanein, Mahmoud; Heusch, Gerd; Huber, Kurt; Hulín, Ivan; Ivanusa, Mario; Krittayaphong, Rungroj; Lau, Chu Pak; Marinskis, Germanas; Mach, François; Moreira, Luiz Felipe; Nieminen, Tuomo; Oukerraj, Latifa; Perings, Stefan; Pierard, Luc; Potpara, Tatjana; Reyes-Caorsi, Walter; Rim, Se Joong; Rødevand, Olaf; Saade, Georges; Sander, Mikael; Shlyakhto, Evgeny; Timuralp, Bilgin; Tousoulis, Dimitris; Ural, Dilek; Piek, J J; Varga, Albert; Lüscher, Thomas F

2017-06-01

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship -emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors´ Network of the European Society of Cardiology.

Data Sharing: A New Editorial Initiative of the International Committee of Medical Journal Editors. Implications for the Editors´ Network

PubMed Central

Alfonso, Fernando; Adamyan, Karlen; Artigou, Jean-Yves; Aschermann, Michael; Boehm, Michael; Buendia, Alfonso; Chu, Pao-Hsien; Cohen, Ariel; Cas, Livio Dei; Dilic, Mirza; Doubell, Anton; Echeverri, Dario; Enç, Nuray; Ferreira-González, Ignacio; Filipiak, Krzysztof J.; Flammer, Andreas; Fleck, Eckart; Gatzov, Plamen; Ginghina, Carmen; Goncalves, Lino; Haouala, Habib; Hassanein, Mahmoud; Heusch, Gerd; Huber, Kurt; Hulín, Ivan; Ivanusa, Mario; Krittayaphong, Rungroj; Lau, Chu-Pak; Marinskis, Germanas; Mach, François; Moreira, Luiz Felipe; Nieminen, Tuomo; Oukerraj, Latifa; Perings, Stefan; Pierard, Luc; Potpara, Tatjana; Reyes-Caorsi, Walter; Rim, Se-Joong; Rødevand, Olaf; Saade, Georges; Sander, Mikael; Shlyakhto, Evgeny; Timuralp, Bilgin; Tousoulis, Dimitris; Ural, Dilek; Piek, J. J.; Varga, Albert; Lüscher, Thomas F.

2017-01-01

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship - emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors´ Network of the European Society of Cardiology. PMID:28591318

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.

The plantaris tendon: a narrative review focusing on anatomical features and clinical importance.

PubMed

Spang, C; Alfredson, H; Docking, S I; Masci, L; Andersson, G

2016-10-01

In recent years, the plantaris tendon has been implicated in the development of chronic painful mid-portion Achilles tendinopathy. In some cases, a thickened plantaris tendon is closely associated with the Achilles tendon, and surgical excision of the plantaris tendon has been reported to be curative in patients who have not derived benefit following conservative treatment and surgical interventions. The aim of this review is to outline the basic aspects of, and the recent research findings, related to the plantaris tendon, covering anatomical and clinical studies including those dealing with histology, imaging and treatment. Cite this article: Bone Joint J 2016;98-B:1312-19. ©2016 The British Editorial Society of Bone & Joint Surgery.

CMV and Immunosenescence: from basics to clinics.

PubMed

Solana, Rafael; Tarazona, Raquel; Aiello, Allison E; Akbar, Arne N; Appay, Victor; Beswick, Mark; Bosch, Jos A; Campos, Carmen; Cantisán, Sara; Cicin-Sain, Luka; Derhovanessian, Evelyna; Ferrando-Martínez, Sara; Frasca, Daniela; Fulöp, Tamas; Govind, Sheila; Grubeck-Loebenstein, Beatrix; Hill, Ann; Hurme, Mikko; Kern, Florian; Larbi, Anis; López-Botet, Miguel; Maier, Andrea B; McElhaney, Janet E; Moss, Paul; Naumova, Elissaveta; Nikolich-Zugich, Janko; Pera, Alejandra; Rector, Jerrald L; Riddell, Natalie; Sanchez-Correa, Beatriz; Sansoni, Paolo; Sauce, Delphine; van Lier, Rene; Wang, George C; Wills, Mark R; Zieliński, Maciej; Pawelec, Graham

2012-10-31

Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been suggested that it drives or at least exacerbates "immunosenescence". This contention remains controversial and was the primary subject of the Third International Workshop on CMV & Immunosenescence which was held in Cordoba, Spain, 15-16th March, 2012. Discussions focused on several main themes including the effects of CMV on adaptive immunity and immunosenescence, characterization of CMV-specific T cells, impact of CMV infection and ageing on innate immunity, and finally, most important, the clinical implications of immunosenescence and CMV infection. Here we summarize the major findings of this workshop.

Cultural differences define diagnosis and genomic medicine practice: implications for undiagnosed diseases program in China.

PubMed

Duan, Xiaohong; Markello, Thomas; Adams, David; Toro, Camilo; Tifft, Cynthia; Gahl, William A; Boerkoel, Cornelius F

2013-09-01

Despite the current acceleration and increasing leadership of Chinese genetics research, genetics and its clinical application have largely been imported to China from the Occident. Neither genetics nor the scientific reductionism underpinning its clinical application is integral to the traditional Chinese worldview. Given that disease concepts and their incumbent diagnoses are historically derived and culturally meaningful, we hypothesize that the cultural expectations of genetic diagnoses and medical genetics practice differ between the Occident and China. Specifically, we suggest that an undiagnosed diseases program in China will differ from the recently established Undiagnosed Diseases Program at the United States National Institutes of Health; a culturally sensitive concept will integrate traditional Chinese understanding of disease with the scientific reductionism of Occidental medicine.

Toward an integrative understanding of narrative and emotion processes in Emotion-focused therapy of depression: implications for theory, research and practice.

PubMed

Angus, Lynne

2012-01-01

This paper addresses the fundamental contributions of client narrative disclosure in psychotherapy and its importance for the elaboration of new emotional meanings and self understanding in the context of Emotion-focused therapy (EFT) of depression. An overview of the multi-methodological steps undertaken to empirically investigate the contributions of client story telling, emotional differentiation and meaning-making processes (Narrative Processes Coding System; Angus et al., 1999) in EFT treatments of depression is provided, followed by a summary of key research findings that informed the development of a narrative-informed approach to Emotion-focused therapy of depression (Angus & Greenberg, 2011). Finally, the clinical practice and training implications of adopting a research-informed approach to working with narrative and emotion processes in EFT are described, and future research directions discussed.

High risk of hypogonadism after traumatic brain injury: clinical implications.

PubMed

Agha, Amar; Thompson, Christopher J

2005-01-01

Several recent studies have convincingly documented a close association between traumatic brain injury (TBI) and pituitary dysfunction. Post-traumatic hypogonadism is very common in the acute post-TBI phase, though most cases recover within six to twelve months following trauma. The functional significance of early hypogonadism, which may reflect adaptation to acute illness, is not known. Hypogonadism persists, however, in 10-17% of long-term survivors. Sex steroid deficiency has implications beyond psychosexual function and fertility for survivors of TBI. Muscle weakness may impair functional recovery from trauma and osteoporosis may be exacerbated by immobility secondary to trauma. Identification and appropriate and timely management of post-traumatic hypogonadism is important in order to optimise patient recovery from head trauma, improve quality of life and avoid the long-term adverse consequences of untreated sex steroid deficiency.

Genetic and molecular alterations in pancreatic cancer: implications for personalized medicine.

PubMed

Fang, Yantian; Yao, Qizhi; Chen, Zongyou; Xiang, Jianbin; William, Fisher E; Gibbs, Richard A; Chen, Changyi

2013-10-31

Recent advances in human genomics and biotechnologies have profound impacts on medical research and clinical practice. Individual genomic information, including DNA sequences and gene expression profiles, can be used for prediction, prevention, diagnosis, and treatment for many complex diseases. Personalized medicine attempts to tailor medical care to individual patients by incorporating their genomic information. In a case of pancreatic cancer, the fourth leading cause of cancer death in the United States, alteration in many genes as well as molecular profiles in blood, pancreas tissue, and pancreas juice has recently been discovered to be closely associated with tumorigenesis or prognosis of the cancer. This review aims to summarize recent advances of important genes, proteins, and microRNAs that play a critical role in the pathogenesis of pancreatic cancer, and to provide implications for personalized medicine in pancreatic cancer.

The role of an NHS library service in the UK: the perceptions of clinical managers in Portsmouth, UK.

PubMed

Blagden, Pauline

2007-06-01

Portsmouth NHS Library Service is exploring methods of raising its profile within its host organization and wishes to demonstrate its contribution to achieving organizational goals, perhaps by means of an impact study. The objective of this small scale study, regarded as a possible precursor to an impact study, was to identify areas where there is potential to increase awareness among clinical managers of the Library's contribution. An e-mail survey was sent to clinical managers to elicit their opinions regarding the contribution of the Library Service to organizational goals. Perhaps unsurprisingly, the role of the Library Service in education, research and effectiveness was most widely recognized. Of responses, 30/42 (71%) rated it as 'very important' and a further 11 (26%) rated it as 'important'. The low appreciation of the Library Service to Clinical Services is a disappointment in view of the body of research evidence. Only 12 respondents (29%) thought that the Library Service contributed 'significantly' by 'supporting informed and timely clinical decision making'. The study suggested areas where there might be scope to raise awareness of the Library contribution. In considering how best to achieve this, the benefits need to be weighed against the resource implications. Portsmouth NHS Library Service decided to increase its marketing efforts but not to carry out an impact study in the short term.

Clinical trials recruitment planning: A proposed framework from the Clinical Trials Transformation Initiative.

PubMed

Huang, Grant D; Bull, Jonca; Johnston McKee, Kelly; Mahon, Elizabeth; Harper, Beth; Roberts, Jamie N

2018-03-01

Patient recruitment is widely recognized as a key determinant of success for clinical trials. Yet a substantial number of trials fail to reach recruitment goals-a situation that has important scientific, financial, ethical, and policy implications. Further, there are important effects on stakeholders who directly contribute to the trial including investigators, sponsors, and study participants. Despite efforts over multiple decades to identify and address barriers, recruitment challenges persist. To advance a more comprehensive approach to trial recruitment, the Clinical Trials Transformation Initiative (CTTI) convened a project team to examine the challenges and to issue actionable, evidence-based recommendations for improving recruitment planning that extend beyond common study-specific strategies. We describe our multi-stakeholder effort to develop a framework that delineates three areas essential to strategic recruitment planning efforts: (1) trial design and protocol development, (2) trial feasibility and site selection, and (3) communication. Our recommendations propose an upstream approach to recruitment planning that has the potential to produce greater impact and reduce downstream barriers. Additionally, we offer tools to help facilitate adoption of the recommendations. We hope that our framework and recommendations will serve as a guide for initial efforts in clinical trial recruitment planning irrespective of disease or intervention focus, provide a common basis for discussions in this area and generate targets for further analysis and continual improvement. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Pharmacogenomics of CYP2C9: Functional and Clinical Considerations†

PubMed Central

Rettie, Allan E.; Fowler, Douglas M.; Miners, John O.

2017-01-01

CYP2C9 is the most abundant CYP2C subfamily enzyme in human liver and the most important contributor from this subfamily to drug metabolism. Polymorphisms resulting in decreased enzyme activity are common in the CYP2C9 gene and this, combined with narrow therapeutic indices for several key drug substrates, results in some important issues relating to drug safety and efficacy. CYP2C9 substrate selectivity is detailed and, based on crystal structures for the enzyme, we describe how CYP2C9 catalyzes these reactions. Factors relevant to clinical response to CYP2C9 substrates including inhibition, induction and genetic polymorphism are discussed in detail. In particular, we consider the issue of ethnic variation in pattern and frequency of genetic polymorphisms and clinical implications. Warfarin is the most well studied CYP2C9 substrate; recent work on use of dosing algorithms that include CYP2C9 genotype to improve patient safety during initiation of warfarin dosing are reviewed and prospects for their clinical implementation considered. Finally, we discuss a novel approach to cataloging the functional capabilities of rare ‘variants of uncertain significance’, which are increasingly detected as more exome and genome sequencing of diverse populations is conducted. PMID:29283396

The Human Microbiome and Understanding the 16S rRNA Gene in Translational Nursing Science

PubMed Central

Ames, Nancy J.; Ranucci, Alexandra; Moriyama, Brad; Wallen, Gwenyth R.

2017-01-01

Background As more is understood regarding the human microbiome, it is increasingly important for nurse scientists and health care practitioners to analyze these microbial communities and their role in health and disease.16S rRNA sequencing is a key methodology in identifying these bacterial populations that has recently transitioned from use primarily in research to having increased utility in clinical settings. Objectives The objectives of this review are to: (a) describe 16S rRNA sequencing and its role in answering research questions important to nursing science; (b) provide an overview of the oral, lung and gut microbiomes and relevant research; and (c) identify future implications for microbiome research and 16S sequencing in translational nursing science. Discussion Sequencing using the 16S rRNA gene has revolutionized research and allowed scientists to easily and reliably characterize complex bacterial communities. This type of research has recently entered the clinical setting, one of the best examples involving the use of 16S sequencing to identify resistant pathogens, thereby improving the accuracy of bacterial identification in infection control. Clinical microbiota research and related requisite methods are of particular relevance to nurse scientists—individuals uniquely positioned to utilize these techniques in future studies in clinical settings. PMID:28252578

Adolescent athletes: psychosocial challenges and clinical concerns.

PubMed

Tamminen, Katherine A; Holt, Nicholas L; Crocker, Peter R E

2012-07-01

To review the recent literature (over the past 18 months) regarding psychosocial challenges and clinical concerns among adolescent athletes, and to address the advances made in understanding adolescent athletes' coping processes. Coping research has moved from identifying discrete stressors and coping strategies to examining the processes of coping over time. Parents and coaches play an important role in young athletes' sport experiences and athletes' use and development of coping strategies. In terms of clinical concerns, findings regarding the prevalence of disordered eating have been equivocal. However, disordered eating may be of greater concern among athletes participating in 'leanness' sports. Sport participation may contribute to increased alcohol consumption among adolescent athletes but decreased use of drugs and smoking cigarettes, while steroid use appears to be relatively rare compared with athletes' use of alcohol and cigarettes. The reviewed studies have implications for future research by identifying opportunities for intervention and education regarding clinical and nonclinical psychosocial challenges. Researchers have emphasized the importance of athletes' social context and relationships in coping with psychosocial challenges in sport. One concern is that adolescent athletes' disordered eating and substance use may reflect maladaptive coping. Experimental and intervention research is limited; however, incorporating members of athletes' social network into future research and interventions may be a practical avenue to achieving positive outcomes among adolescent athletes.

Factors Influencing Clinical Correlates of Chronic Traumatic Encephalopathy (CTE): A Review

PubMed Central

Asken, Breton M.; Sullan, Molly J.; Snyder, Aliyah R.; Houck, Zachary M.; Bryant, Vaughn E.; Hizel, Loren P.; McLaren, Molly E.; Dede, Duane E.; Jaffee, Michael S.; DeKosky, Steven T.; Bauer, Russell M.

2017-01-01

Chronic traumatic encephalopathy (CTE) is a neuropathologically defined disease reportedly linked to a history of repetitive brain trauma. As such, retired collision sport athletes are likely at heightened risk for developing CTE. Researchers have described distinct pathological features of CTE as well a wide range of clinical symptom presentations, recently termed traumatic encephalopathy syndrome (TES). These clinical symptoms are highly variable, non-specific to individuals described as having CTE pathology in case reports, and are often associated with many other factors. This review describes the cognitive, emotional, and behavioral changes associated with 1) developmental and demographic factors, 2) neurodevelopmental disorders, 3) normal aging, 4) adjusting to retirement, 5) drug and alcohol abuse, 6) surgeries and anesthesia, and 7) sleep difficulties, as well as the relationship between these factors and risk for developing dementia-related neurodegenerative disease. We discuss why some professional athletes may be particularly susceptible to many of these effects and the importance of choosing appropriate controls groups when designing research protocols. We conclude that these factors should be considered as modifiers predominantly of the clinical outcomes associated with repetitive brain trauma within a broader biopsychosocial framework when interpreting and attributing symptom development, though also note potential effects on neuropathological outcomes. Importantly, this could have significant treatment implications for improving quality of life. PMID:27561662

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

Continuing Need for Sexually Transmitted Disease Clinics After the Affordable Care Act

PubMed Central

Parsell, Bradley W.; Leichliter, Jami S.; Habel, Melissa A.; Tao, Guoyu; Pearson, William S.; Gift, Thomas L.

2015-01-01

Objectives. We assessed the characteristics of sexually transmitted disease (STD) clinic patients, their reasons for seeking health services in STD clinics, and their access to health care in other venues. Methods. In 2013, we surveyed persons who used publicly funded STD clinics in 21 US cities with the highest STD morbidity. Results. Of the 4364 STD clinic patients we surveyed, 58.5% were younger than 30 years, 72.5% were non-White, and 49.9% were uninsured. They visited the clinic for STD symptoms (18.9%), STD screening (33.8%), and HIV testing (13.6%). Patients chose STD clinics because of walk-in, same-day appointments (49.5%), low cost (23.9%), and expert care (8.3%). Among STD clinic patients, 60.4% had access to another type of venue for sick care, and 58.5% had access to another type of venue for preventive care. Most insured patients (51.6%) were willing to use insurance to pay for care at the STD clinic. Conclusions. Despite access to other health care settings, patients chose STD clinics for sexual health care because of convenient, low-cost, and expert care. Policy Implication. STD clinics play an important role in STD prevention by offering walk-in care to uninsured patients. PMID:26447908

Screening for important unwarranted variation in clinical practice: a triple-test of processes of care, costs and patient outcomes.

PubMed

Partington, Andrew; Chew, Derek P; Ben-Tovim, David; Horsfall, Matthew; Hakendorf, Paul; Karnon, Jonathan

2017-03-01

Objective Unwarranted variation in clinical practice is a target for quality improvement in health care, but there is no consensus on how to identify such variation or to assess the potential value of initiatives to improve quality in these areas. This study illustrates the use of a triple test, namely the comparative analysis of processes of care, costs and outcomes, to identify and assess the burden of unwarranted variation in clinical practice. Methods Routinely collected hospital and mortality data were linked for patients presenting with symptoms suggestive of acute coronary syndromes at the emergency departments of four public hospitals in South Australia. Multiple regression models analysed variation in re-admissions and mortality at 30 days and 12 months, patient costs and multiple process indicators. Results After casemix adjustment, an outlier hospital with statistically significantly poorer outcomes and higher costs was identified. Key process indicators included admission patterns, use of invasive diagnostic procedures and length of stay. Performance varied according to patients' presenting characteristics and time of presentation. Conclusions The joint analysis of processes, outcomes and costs as alternative measures of performance inform the importance of reducing variation in clinical practice, as well as identifying specific targets for quality improvement along clinical pathways. Such analyses could be undertaken across a wide range of clinical areas to inform the potential value and prioritisation of quality improvement initiatives. What is known about the topic? Variation in clinical practice is a long-standing issue that has been analysed from many different perspectives. It is neither possible nor desirable to address all forms of variation in clinical practice: the focus should be on identifying important unwarranted variation to inform actions to reduce variation and improve quality. What does this paper add? This paper proposes the comparative analysis of processes of care, costs and outcomes for patients with similar diagnoses presenting at alternative hospitals, using linked, routinely collected data. This triple test of performance indicators extracts maximum value from routine data to identify priority areas for quality improvement to reduce important and unwarranted variations in clinical practice. What are the implications for practitioners? The proposed analyses need to be applied to other clinical areas to demonstrate the general application of the methods. The outputs can then be validated through the application of quality improvement initiatives in clinical areas with identified important and unwarranted variation. Validated frameworks for the comparative analysis of clinical practice provide an efficient approach to valuing and prioritising actions to improve health service quality.

From 'implications' to 'dimensions': science, medicine and ethics in society.

PubMed

Pickersgill, Martyn D

2013-03-01

Much bioethical scholarship is concerned with the social, legal and philosophical implications of new and emerging science and medicine, as well as with the processes of research that under-gird these innovations. Science and technology studies (STS), and the related and interpenetrating disciplines of anthropology and sociology, have also explored what novel technoscience might imply for society, and how the social is constitutive of scientific knowledge and technological artefacts. More recently, social scientists have interrogated the emergence of ethical issues: they have documented how particular matters come to be regarded as in some way to do with 'ethics', and how this in turn enjoins particular types of social action. In this paper, I will discuss some of this and other STS (and STS-inflected) literature and reflect on how it might complement more 'traditional' modes of bioethical enquiry. I argue that STS might (1) cast new light on current bioethical issues, (2) direct the gaze of bioethicists towards matters that may previously have escaped their attention, and (3) indicate the import not only of the ethical implications of biomedical innovation, but also how these innovative and other processes feature ethics as a dimension of everyday laboratory and clinical work. In sum, engagements between STS and bioethics are increasingly important in order to understand and manage the complex dynamics between science, medicine and ethics in society.

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.

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.

Quantifying factors for the success of stratified medicine.

PubMed

Trusheim, Mark R; Burgess, Breon; Hu, Sean Xinghua; Long, Theresa; Averbuch, Steven D; Flynn, Aiden A; Lieftucht, Alfons; Mazumder, Abhijit; Milloy, Judy; Shaw, Peter M; Swank, David; Wang, Jian; Berndt, Ernst R; Goodsaid, Federico; Palmer, Michael C

2011-10-31

Co-developing a drug with a diagnostic to create a stratified medicine - a therapy that is targeted to a specific patient population on the basis of a clinical characteristic such as a biomarker that predicts treatment response - presents challenges for product developers, regulators, payers and physicians. With the aim of developing a shared framework and tools for addressing these challenges, here we present an analysis using data from case studies in oncology and Alzheimer's disease, coupled with integrated computational modelling of clinical outcomes and developer economic value, to quantify the effects of decisions related to key issues such as the design of clinical trials. This illustrates how such analyses can aid the coordination of diagnostic and drug development, and the selection of optimal development and commercialization strategies. It also illustrates the impact of the interplay of these factors on the economic feasibility of stratified medicine, which has important implications for public policy makers.

Reasoning, evidence, and clinical decision-making: The great debate moves forward.

PubMed

Loughlin, Michael; Bluhm, Robyn; Buetow, Stephen; Borgerson, Kirstin; Fuller, Jonathan

2017-10-01

When the editorial to the first philosophy thematic edition of this journal was published in 2010, critical questioning of underlying assumptions, regarding such crucial issues as clinical decision making, practical reasoning, and the nature of evidence in health care, was still derided by some prominent contributors to the literature on medical practice. Things have changed dramatically. Far from being derided or dismissed as a distraction from practical concerns, the discussion of such fundamental questions, and their implications for matters of practical import, is currently the preoccupation of some of the most influential and insightful contributors to the on-going evidence-based medicine debate. Discussions focus on practical wisdom, evidence, and value and the relationship between rationality and context. In the debate about clinical practice, we are going to have to be more explicit and rigorous in future in developing and defending our views about what is valuable in human life. © 2017 John Wiley & Sons, Ltd.

Novel Hypothesis to Explain Why SGLT2 Inhibitors Inhibit Only 30–50% of Filtered Glucose Load in Humans

PubMed Central

Abdul-Ghani, Muhammad A.; DeFronzo, Ralph A.; Norton, Luke

2013-01-01

Inhibitors of sodium-glucose cotransporter 2 (SGLT2) are a novel class of antidiabetes drugs, and members of this class are under various stages of clinical development for the management of type 2 diabetes mellitus (T2DM). It is widely accepted that SGLT2 is responsible for >80% of the reabsorption of the renal filtered glucose load. However, maximal doses of SGLT2 inhibitors fail to inhibit >50% of the filtered glucose load. Because the clinical efficacy of this group of drugs is entirely dependent on the amount of glucosuria produced, it is important to understand why SGLT2 inhibitors inhibit <50% of the filtered glucose load. In this Perspective, we provide a novel hypothesis that explains this apparent puzzle and discuss some of the clinical implications inherent in this hypothesis. PMID:24065789

The social individual in clinical ethics.

PubMed

Moreno, Jonathan D

1992-01-01

Except for several provocative final sentences, Sigrid Fry-Revere's "A Libertarian Critique of H. Tristram Engelhardt, Jr.'s The Foundations of Bioethics" is not a libertarian so much as it is a philosophical critique. Engelhardt's work has been widely reviewed, and its arguments have been discussed in Fry-Revere's article and elsewhere. Although it would be impractical in this context to undertake the development of a full-scale, philosophical alternative to libertarianism in bioethics, some recent work in philosophy and clinical ethics bears strongly on the challenge that Engelhardt's work represents. In this commentary I will focus on the implications of a certain alternative philosophy -- and by comparison the limitations of Engelhardt's libertarianism -- for one important aspect of clinical ethics: our understanding of the nature of individuality, with special reference to the situation of the patient. I write as an admiring critic of Engelhardt's work, from which I have learned and drawn inspiration....

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.

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.

TURNING IT UPSIDE DOWN: AREAS OF PRESERVED COGNITIVE FUNCTION IN SCHIZOPHRENIA

PubMed Central

Gold, James M.; Hahn, Britta; Strauss, Gregory P.; Waltz, James A.

2013-01-01

Patients with schizophrenia demonstrate marked impairments on most clinical neuropsychological tests. These findings suggest that patients suffer from a generalized form of cognitive impairment, with little evidence of spared performance documented in several large meta-analytic reviews of the clinical literature. In contrast, we review evidence for relative sparing of aspects of attention, procedural memory, and emotional processing observed in studies that have employed experimental approaches adapted from the cognitive and affective neuroscience literature. These islands of preserved performance suggest that the cognitive deficits in schizophrenia are not as general as they appear to be when assayed with clinical neuropsychological methods. The apparent contradiction in findings across methods may offer important clues about the nature of cognitive impairment in schizophrenia. The documentation of preserved cognitive function in schizophrenia may serve to sharpen hypotheses about the biological mechanisms that are implicated in the illness. PMID:19452280

The law of diminishing returns in clinical medicine: how much risk reduction is enough?

PubMed

Mold, James W; Hamm, Robert M; McCarthy, Laine H

2010-01-01

The law of diminishing returns, first described by economists to explain why, beyond a certain point, additional inputs produce smaller and smaller outputs, offers insight into many situations encountered in clinical medicine. For example, when the risk of an adverse event can be reduced in several different ways, the impact of each intervention can generally be shown mathematically to be reduced by the previous ones. The diminishing value of successive interventions is further reduced by adverse consequences (eg, drug-drug, drug-disease, and drug-nutrient interactions), as well as by the total expenditures of time, energy, and resources, which increase with each additional intervention. It is therefore important to try to prioritize interventions based on patient-centered goals and the relative impact and acceptability of the interventions. We believe that this has implications for clinical practice, research, and policy.

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

Exercise intolerance in pulmonary hypertension: mechanism, evaluation and clinical implications.

PubMed

Babu, Abraham Samuel; Arena, Ross; Myers, Jonathan; Padmakumar, Ramachandran; Maiya, Arun G; Cahalin, Lawrence P; Waxman, Aaron B; Lavie, Carl J

2016-09-01

Exercise intolerance in pulmonary hypertension (PH) is a major factor affecting activities of daily living and quality of life. Evaluation strategies (i.e., non-invasive and invasive tests) are integral to providing a comprehensive assessment of clinical and functional status. Despite a growing body of literature on the clinical consequences of PH, there are limited studies discussing the contribution of various physiological systems to exercise intolerance in this patient population. This review, through a search of various databases, describes the physiological basis for exercise intolerance across the various PH etiologies, highlights the various exercise evaluation methods and discusses the rationale for exercise training amongst those diagnosed with PH. Expert commentary: With the growing importance of evaluating exercise capacity in PH (class 1, Level C recommendation), understanding why exercise performance is altered in PH is crucial. Thus, the further study is required for better quality evidence in this area.

Listening to a patient: An exploratory experimental investigation into the effects of vocalization and therapist gender on interpreting clinical material.

PubMed

Dauphin, Barry; Halverson, Stacey; Pouliot, Sarah; Slowik, Linda

2018-01-01

Carefully listening to the patient is of paramount importance for psychoanalysis and psychoanalytic psychotherapy. The present study explored whether patient vocalization as well as the gender of the analyst play significant roles in clinical listening. Fifty-one psychoanalysts and psychoanalytic therapists were randomly assigned to listen to one of two dramatized psychoanalytic sessions. The content of the sessions was the same for both versions, but the sessions were dramatized differently. Some differences emerged between the versions, especially on ratings of reality testing, impulse control, pressured speech, patient was confusing, and awareness of imagery. Furthermore, differences emerged between male and female analysts in terms of ratings of intervention strategies and countertransference reactions to the patient material. Session version and gender affect different ratings. Implications of the findings are discussed as is the utility of using more ecologically valid material in conducting empirical research into clinical judgment.

The timing of exposure in clinic-based treatment for childhood anxiety disorders.

PubMed

Gryczkowski, Michelle R; Tiede, Michael S; Dammann, Julie E; Jacobsen, Amy Brown; Hale, Lisa R; Whiteside, Stephen P H

2013-03-01

The present study examines treatment length and timing of exposure from two child anxiety disorders clinics. Data regarding symptoms and treatment characteristics for 28 youth were prospectively obtained through self, parent, and therapist report at each session. Information regarding length of treatment, timing of exposure initiation, and drop-out rates were compared with those obtained through efficacy and effectiveness trials of manualized treatment for anxious youth. Findings from the authors' clinical data revealed significantly shorter treatment duration with exposures implemented sooner than in the previous studies. Dropout rates were significantly higher than in the efficacy trial but comparable with the effectiveness trial. Outcome data from a subset of eight patients revealed large effect sizes. These findings suggest that effective treatment can be shorter and more focused on exposure than is often outlined in manuals and have important implications for outcome research and dissemination.

Self-efficacy in weight management.

PubMed

Clark, M M; Abrams, D B; Niaura, R S; Eaton, C A; Rossi, J S

1991-10-01

Self-efficacy is an important mediating mechanism in advancing understanding of the treatment of obesity. This study developed and validated the Weight Efficacy Life-Style Questionnaire (WEL), improving on previous studies by the use of clinical populations, cross-validation of the initial factor analysis, exploration of the best fitting theoretical model of self-efficacy, and examination of change in treatment. The resulting 20-item WEL consists of five situational factors: Negative Emotions, Availability, Social Pressure, Physical Discomfort, and Positive Activities. A hierarchical model was found to provide the best fit to the data. Results from two separate clinical treatment studies (total N = 382) show that the WEL is sensitive to changes in global scores as well as to a subset of the five situational factor scores. Treatment programs may be incomplete if they change only a subset of the situational dimensions of self-efficacy. Theoretical and clinical implications are discussed.

Implications of ICD-10 for Sarcopenia Clinical Practice and Clinical Trials: Report by the International Conference on Frailty and Sarcopenia Research Task Force.

PubMed

Vellas, B; Fielding, R A; Bens, C; Bernabei, R; Cawthon, P M; Cederholm, T; Cruz-Jentoft, A J; Del Signore, S; Donahue, S; Morley, J; Pahor, M; Reginster, J-Y; Rodriguez Mañas, L; Rolland, Y; Roubenoff, R; Sinclair, A; Cesari, M

2018-01-01

Establishment of an ICD-10-CM code for sarcopenia in 2016 was an important step towards reaching international consensus on the need for a nosological framework of age-related skeletal muscle decline. The International Conference on Frailty and Sarcopenia Research Task Force met in April 2017 to discuss the meaning, significance, and barriers to the implementation of the new code as well as strategies to accelerate development of new therapies. Analyses by the Sarcopenia Definitions and Outcomes Consortium are underway to develop quantitative definitions of sarcopenia. A consensus conference is planned to evaluate this analysis. The Task Force also discussed lessons learned from sarcopenia trials that could be applied to future trials, as well as lessons from the osteoporosis field, a clinical condition with many constructs similar to sarcopenia and for which ad hoc treatments have been developed and approved by regulatory agencies.

Experimental anti-GBM disease as a tool for studying spontaneous lupus nephritis.

PubMed

Fu, Yuyang; Du, Yong; Mohan, Chandra

2007-08-01

Lupus nephritis is an immune-mediated disease, where antibodies and T cells both play pathogenic roles. Since spontaneous lupus nephritis in mouse models takes 6-12 months to manifest, there is an urgent need for a mouse model that can be used to delineate the pathogenic processes that lead to immune nephritis, over a quicker time frame. We propose that the experimental anti-glomerular basement membrane (GBM) disease model might be a suitable tool for uncovering some of the molecular steps underlying lupus nephritis. This article reviews the current evidence that supports the use of the experimental anti-GBM nephritis model for studying spontaneous lupus nephritis. Importantly, out of about 25 different molecules that have been specifically examined in the experimental anti-GBM model and also spontaneous lupus nephritis, all influence both diseases concordantly, suggesting that the experimental model might be a useful tool for unraveling the molecular basis of spontaneous lupus nephritis. This has important clinical implications, both from the perspective of genetic susceptibility as well as clinical therapeutics.

Using machine learning for sequence-level automated MRI protocol selection in neuroradiology.

PubMed

Brown, Andrew D; Marotta, Thomas R

2018-05-01

Incorrect imaging protocol selection can lead to important clinical findings being missed, contributing to both wasted health care resources and patient harm. We present a machine learning method for analyzing the unstructured text of clinical indications and patient demographics from magnetic resonance imaging (MRI) orders to automatically protocol MRI procedures at the sequence level. We compared 3 machine learning models - support vector machine, gradient boosting machine, and random forest - to a baseline model that predicted the most common protocol for all observations in our test set. The gradient boosting machine model significantly outperformed the baseline and demonstrated the best performance of the 3 models in terms of accuracy (95%), precision (86%), recall (80%), and Hamming loss (0.0487). This demonstrates the feasibility of automating sequence selection by applying machine learning to MRI orders. Automated sequence selection has important safety, quality, and financial implications and may facilitate improvements in the quality and safety of medical imaging service delivery.

Guanosine triphosphatase activation occurs downstream of calcineurin in cardiac hypertrophy*.

PubMed

Richardson, Kenneth E; Tannous, Paul; Berenji, Kambeez; Nolan, Bridgid; Bayless, Kayla J; Davis, George E; Rothermel, Beverly A; Hill, Joseph A

2005-12-01

There is great interest in deciphering mechanisms of maladaptive remodeling in cardiac hypertrophy in the hope of affording clinical benefit. Potential targets of therapeutic intervention include the cytoplasmic phosphatase calcineurin and small guanosine triphosphate-binding proteins, such as Rac1 and RhoA, all of which have been implicated in maladaptive hypertrophy. However, little is known about the interaction-if any-between these important signaling molecules in hypertrophic heart disease. In this study, we examined the molecular interplay among these molecules, finding that Rho family guanosine triphosphatase signaling occurs either downstream of calcineurin or as a required, parallel pathway. It has been shown that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition blocks hypertrophy, and we report here that "statin" therapy effectively suppresses small G protein activation and blunts hypertrophic growth in vitro and in vivo. Importantly, despite significant suppression of hypertrophy, clinical and hemodynamic markers remained compensated, suggesting that the hypertrophic growth induced by this pathway is not required to maintain circulatory performance.

Clinical and molecular characterisation of hyperinsulinaemic hypoglycaemia in infants born small-for-gestational age

PubMed Central

Arya, Ved Bhushan; Flanagan, Sarah E; Kumaran, Anitha; Shield, Julian P; Ellard, Sian; Hussain, Khalid; Kapoor, Ritika R

2013-01-01

Objective To characterise the phenotype and genotype of neonates born small-for-gestational age (SGA; birth weight <10th centile) who developed hyperinsulinaemic hypoglycaemia (HH). Methods Clinical information was prospectively collected on 27 SGA neonates with HH, followed by sequencing of KCNJ11 and ABCC8. Results There was no correlation between the maximum glucose requirement and serum insulin levels. Serum insulin level was undetectable in five infants (19%) during hypoglycaemia. Six infants (22%) required diazoxide treatment >6 months. Normoglycaemia on diazoxide <5 mg/kg/day was a safe predictor of resolved HH. Sequencing of KCNJ11/ABCC8 did not identify any mutations. Conclusions Serum insulin levels during hypoglycaemia taken in isolation can miss the diagnosis of HH. SGA infants may continue to have hypofattyacidaemic hypoketotic HH beyond the first few weeks of life. Recognition and treatment of this group of patients are important and may have important implications for neurodevelopmental outcome of these patients. PMID:23362136

Experiences of physical and relational victimization in children with ADHD: The role of social problems and aggression.

PubMed

McQuade, Julia D; Breslend, Nicole L; Groff, Destin

2018-04-16

The social risk factors for physical and relational peer victimization were examined within a mixed-gender sample of children with and without attention-deficit/hyperactivity disorder (ADHD). Participants were 124 children (ages 8-12 years; 48% boys), with 47% exhibiting sub-clinical or clinical elevations in ADHD symptoms. ADHD and oppositional defiant disorder (ODD) symptom counts were assessed based on parent- and teacher-reports; parents rated children's social problems and teachers rated children's use of physical and relational aggression and experiences of physical and relational victimization. A multiple mediator model was used to test whether there were indirect effects of ADHD or ODD symptoms on physical and relational victimization through social problems, physical aggression, or relational aggression. At the bivariate level, ADHD and ODD symptoms were both significantly associated with higher rates of physical and relational victimization. In the mediational model, there were significant indirect effects of ADHD symptoms on relational victimization via social problems, of ODD on relational victimization via relational aggression, and of ODD symptoms on physical victimization via physical aggression. Results suggest that there are distinct risk factors implicated in the physical and relational victimization of youth with ADHD and that the co-occurrence of ODD symptoms is important to assess. Clinical implications for addressing victimization in children with ADHD are discussed. © 2018 Wiley Periodicals, Inc.

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.

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.

Patients' perception of epilepsy and threat to self-identity: a qualitative approach.

PubMed

Hosseini, Nazafarin; Sharif, Farkhondeh; Ahmadi, Fazlollah; Zare, Mohammad

2013-10-01

A clinical diagnosis of epilepsy often carries a silent social stigma and is associated with metaphysical forces. This qualitative study aimed to explore the Iranian patients' perception of epilepsy where clinical aspects are more benign than the social implications with long-term psychological consequences. Historically, epilepsy has been known as a form of insanity, madness, sorcery, and possession by evil spirits. Thirty participants consisting of 21 patients with epilepsy, 5 family members, and 4 medical staff were selected from urban and rural medical and health care centers, hospitals, physician offices, outpatient clinics, and the Iranian Epilepsy Association. Unstructured and semistructured interviews were applied to obtain data. Transcribed interviews and field notes were analyzed using qualitative content analysis method. Categories and subcategories emerged from the participants' perceptions of epilepsy and its disruptive effects on their self-identity. The main categories derived from data were 1) a different perspective about epilepsy, 2) self-debasement, and 3) being a burden. The major theme found in this study was "identity loss". Our study results highlight the importance of public awareness among community members and healthcare professionals on how patients with epilepsy experience their disease with psychosocial implications. Understanding patients' perspectives can be essential to developing a comprehensive and holistic care plan for patients with epilepsy and addressing their multidimensional needs. Copyright © 2013 Elsevier Inc. All rights reserved.

Characterization of clinical signs in the human interactome.

PubMed

Chagoyen, Monica; Pazos, Florencio

2016-06-15

Many diseases are related by shared associated molecules and pathways, exhibiting comorbidities and common phenotypes, an indication of the continuous nature of the human pathological landscape. Although it is continuous, this landscape is always partitioned into discrete diseases when studied at the molecular level. Clinical signs are also important phenotypic descriptors that can reveal the molecular mechanisms that underlie pathological states, but have seldom been the subject of systemic research. Here, we quantify the modular nature of the clinical signs associated with genetic diseases in the human interactome. We found that clinical signs are reflected as modules at the molecular network level, to at least to the same extent as diseases. They can thus serve as a valid complementary partition of the human pathological landscape, with implications for etiology research, diagnosis and treatment. monica.chagoyen@cnb.csic.es Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Targeting the androgen receptor in triple-negative breast cancer: current perspectives.

PubMed

Mina, Alain; Yoder, Rachel; Sharma, Priyanka

2017-01-01

Triple-negative breast cancer (TNBC) is an aggressive subtype associated with frequent recurrence and metastasis. Unlike hormone receptor-positive subtypes, treatment of TNBC is currently limited by the lack of clinically available targeted therapies. Androgen signaling is necessary for normal breast development, and its dysregulation has been implicated in breast tumorigenesis. In recent years, gene expression studies have identified a subset of TNBC that is enriched for androgen receptor (AR) signaling. Interference with androgen signaling in TNBC is promising, and AR-inhibiting drugs have shown antitumorigenic activity in preclinical and proof of concept clinical studies. Recent advances in our understanding of androgenic signaling in TNBC, along with the identification of interacting pathways, are allowing development of the next generation of clinical trials with AR inhibitors. As novel AR-targeting agents are developed and evaluated in clinical trials, it is equally important to establish a robust set of biomarkers for identification of TNBC tumors that are most likely to respond to AR inhibition.

Evaluating Random Error in Clinician-Administered Surveys: Theoretical Considerations and Clinical Applications of Interobserver Reliability and Agreement.

PubMed

Bennett, Rebecca J; Taljaard, Dunay S; Olaithe, Michelle; Brennan-Jones, Chris; Eikelboom, Robert H

2017-09-18

The purpose of this study is to raise awareness of interobserver concordance and the differences between interobserver reliability and agreement when evaluating the responsiveness of a clinician-administered survey and, specifically, to demonstrate the clinical implications of data types (nominal/categorical, ordinal, interval, or ratio) and statistical index selection (for example, Cohen's kappa, Krippendorff's alpha, or interclass correlation). In this prospective cohort study, 3 clinical audiologists, who were masked to each other's scores, administered the Practical Hearing Aid Skills Test-Revised to 18 adult owners of hearing aids. Interobserver concordance was examined using a range of reliability and agreement statistical indices. The importance of selecting statistical measures of concordance was demonstrated with a worked example, wherein the level of interobserver concordance achieved varied from "no agreement" to "almost perfect agreement" depending on data types and statistical index selected. This study demonstrates that the methodology used to evaluate survey score concordance can influence the statistical results obtained and thus affect clinical interpretations.

Cognitive processes during acute psychosis: the role of heightened responsibility and catastrophic misinterpretations.

PubMed

Luzón, Olga; Harrop, Chris; Nolan, Fiona

2009-07-01

This study investigated the role of cognitive mechanisms underlying obsessive compulsive and panic disorders in psychosis, and in particular, their possible contributions to acute psychosis. A total of 90 participants were recruited comprising three equal-size groups, including two clinical groups (acute and stable) and one non-clinical matched control group. Symptom severity and distress was assessed using the PSYRATS, and questionnaire measures of anxiety and obsessive beliefs were administered to all participants. Individuals with a diagnosis of psychosis reported significantly higher levels of obsessional beliefs and anxiety sensitivity than the non-clinical group. Furthermore, acutely psychotic patients reported a significantly higher sense of responsibility and catastrophic misinterpretation than the stable psychiatric controls, and than samples of OCD and GAD patients. Results suggest that these anxiety processes are particularly important during acute psychotic episodes, beyond the reported comorbidity. The theoretical and clinical implications of these findings, the limitations of the methodology employed, and suggestions for future research are discussed.

An analysis of clinical reasoning through a recent and comprehensive approach: the dual-process theory

PubMed Central

Pelaccia, Thierry; Tardif, Jacques; Triby, Emmanuel; Charlin, Bernard

2011-01-01

Context Clinical reasoning plays a major role in the ability of doctors to make diagnoses and decisions. It is considered as the physician's most critical competence, and has been widely studied by physicians, educationalists, psychologists and sociologists. Since the 1970s, many theories about clinical reasoning in medicine have been put forward. Purpose This paper aims at exploring a comprehensive approach: the “dual-process theory”, a model developed by cognitive psychologists over the last few years. Discussion After 40 years of sometimes contradictory studies on clinical reasoning, the dual-process theory gives us many answers on how doctors think while making diagnoses and decisions. It highlights the importance of physicians’ intuition and the high level of interaction between analytical and non-analytical processes. However, it has not received much attention in the medical education literature. The implications of dual-process models of reasoning in terms of medical education will be discussed. PMID:21430797

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.

PHEOCHROMOCYTOMA: IMPLICATIONS IN TUMORIGENESIS AND THE ACTUAL MANAGEMENT

PubMed Central

Shah, Urvi; Giubellino, Alessio; Pacak, Karel

2012-01-01

Pheochromocytomas and paragangliomas are rare neuroendocrine catecholamine producing tumors with varied clinical presentations, biochemistries and genetic makeup. These features outline the complexity and the difficulties in studying and understanding the oncogenesis of these tumors. The study of families with genetically inherited mutations in pheochromocytoma susceptibility genes has greatly enhanced our understanding of the pathophysiology and mechanisms of oncogenesis of the disease, and consequently changed our clinical approach. Several molecular pathways and mutations in their important regulatory proteins have been identified. Such mutations are responsible for the dysregulation of metabolic pathways involved in oxygen and nutrient sensing, apoptosis regulation, cell proliferation, migration and invasion. The knowledge derived from the study of these pathways will be fundamental in the future clinical management of these patients. As a rare disease that often masks its clinical presentation, the diagnosis is frequently missed and a high level of suspicion is required. Management of this disease requires a multidisciplinary team approach and has been discussed along with advances in its treatment. PMID:22691888

Pheochromocytoma: implications in tumorigenesis and the actual management.

PubMed

Shah, U; Giubellino, A; Pacak, K

2012-06-01

Pheochromocytomas and paragangliomas are rare neuroendocrine catecholamine producing tumors with varied clinical presentations, biochemistries and genetic makeup. These features outline the complexity and the difficulties in studying and understanding the oncogenesis of these tumors. The study of families with genetically inherited mutations in pheochromocytoma susceptibility genes has greatly enhanced our understanding of the pathophysiology and mechanisms of oncogenesis of the disease, and consequently changed our clinical approach. Several molecular pathways and mutations in their important regulatory proteins have been identified. Such mutations are responsible for the dysregulation of metabolic pathways involved in oxygen and nutrient sensing, apoptosis regulation, cell proliferation, migration and invasion. The knowledge derived from the study of these pathways will be fundamental in the future clinical management of these patients. As a rare disease that often masks its clinical presentation, the diagnosis is frequently missed and a high level of suspicion is required. Management of this disease requires a multidisciplinary team approach and will be discussed along with advances in its treatment.

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:…

Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review

PubMed Central

Muturi-Kioi, Vincent; Lewis, David; Launay, Odile; Leroux-Roels, Geert; Anemona, Alessandra; Loulergue, Pierre; Bodinham, Caroline L.; Aerssens, Annelies; Groth, Nicola; Saul, Allan; Podda, Audino

2016-01-01

Background In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance. Methodology We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context. Principal Findings Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations. Conclusions It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events. Trial registration ClinicalTrials.gov NCT02017899, NCT02034500, NCT01771367, NCT01765413, NCT02523287 PMID:27490698

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

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.

The Athletic Shoe in Football

PubMed Central

Jastifer, James; Kent, Richard; Crandall, Jeff; Sherwood, Chris; Lessley, David; McCullough, Kirk A.; Coughlin, Michael J.; Anderson, Robert B.

2017-01-01

Background: Foot and ankle injuries are common in sports, particularly in cleated athletes. Traditionally, the athletic shoe has not been regarded as a piece of protective equipment but rather as a part of the uniform, with a primary focus on performance and subjective feedback measures of comfort. Changes in turf and shoe design have poorly understood implications on the health and safety of players. Evidence Acquisition: A literature search of the MEDLINE and PubMed databases was conducted. Keywords included athletic shoewear, cleated shoe, football shoes, and shoewear, and search parameters were between the years 2000 and 2016. Study Design: Clinical review. Level of Evidence: Level 5. Results: The athletic shoe is an important piece of protective sports equipment. There are several important structural considerations of shoe design, including biomechanical compliance, cleat and turf interaction, and shoe sizing/fit, that affect the way an athlete engages with the playing surface and carry important potential implications regarding player safety if not understood and addressed. Conclusion: Athletic footwear should be considered an integral piece of protective equipment rather than simply an extension of the uniform apparel. More research is needed to define optimal shoe sizing, the effect that design has on mechanical load, and how cleat properties, including pattern and structure, interact with the variety of playing surfaces. PMID:28151702

Post-transcriptional regulation in hematopoiesis: RNA binding proteins take control.

PubMed

de Rooij, Laura P M H; Chan, Derek C H; Keyvani Chahi, Ava; Hope, Kristin J

2018-06-13

Normal hematopoiesis is sustained through a carefully orchestrated balance between hematopoietic stem cell (HSC) self-renewal and differentiation. The functional importance of this axis is underscored by the severity of disease phenotypes initiated by abnormal HSC function, including myelodysplastic syndromes and hematopoietic malignancies. Major advances in the understanding of transcriptional regulation of primitive hematopoietic cells have been achieved, however, the post-transcriptional regulatory layer that may impinge on their behavior remains underexplored by comparison. Key players at this level include RNA binding proteins (RBPs), which execute precise and highly coordinated control of gene expression through modulation of RNA properties that include its splicing, polyadenylation, localization, degradation or translation. With the recent identification of RBPs having essential roles in regulating proliferation and cell fate decisions in other systems, there has been an increasing appreciation of the importance of post-transcriptional control at the stem cell level. Here we discuss our current understanding of RBP-driven post-transcriptional regulation in HSC, its implications for normal, perturbed and malignant hematopoiesis, as well as the most recent technological innovations aimed at RBP-RNA network characterization at the systems level. Emerging evidence highlights RBP-driven control as an underappreciated feature of primitive hematopoiesis, the greater understanding of which has important clinical implications.

Consequences of Circadian and Sleep Disturbances for the Cardiovascular System.

PubMed

Alibhai, Faisal J; Tsimakouridze, Elena V; Reitz, Cristine J; Pyle, W Glen; Martino, Tami A

2015-07-01

Circadian rhythms play a crucial role in our cardiovascular system. Importantly, there has been a recent flurry of clinical and experimental studies revealing the profound adverse consequences of disturbing these rhythms on the cardiovascular system. For example, circadian disturbance worsens outcome after myocardial infarction with implications for patients in acute care settings. Moreover, disturbing rhythms exacerbates cardiac remodelling in heart disease models. Also, circadian dyssynchrony is a causal factor in the pathogenesis of heart disease. These discoveries have profound implications for the cardiovascular health of shift workers, individuals with circadian and sleep disorders, or anyone subjected to the 24/7 demands of society. Moreover, these studies give rise to 2 new frontiers for translational research: (1) circadian rhythms and the cardiac sarcomere, which sheds new light on our understanding of myofilament structure, signalling, and electrophysiology; and (2) knowledge translation, which includes biomarker discovery (chronobiomarkers), timing of therapies (chronotherapy), and other new promising approaches to improve the management and treatment of cardiovascular disease. Reconsidering circadian rhythms in the clinical setting benefits repair mechanisms, and offers new promise for patients. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

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

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.

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 ischemic liver cirrhosis theory and its clinical implications.

PubMed

Mancuso, Andrea

2016-09-01

The canonical pathway theory of cirrhosis addresses inflammation as the main driver of hepatic fibrogenesis in hepatitis, so needing a further hypothesis for etiologies missing inflammation, for which parenchymal extinction is postulated. The present paper reports an alternative hypothesis suggesting a central role of micro-vascular ischemia in fibrogenesis and cirrhosis development, whatever is the aetiology of liver chronic injury. In fact, since chronic liver injury could finally result in endothelial damage and micro-vascular thrombosis, leading to a trigger of inappropriate hepatocyte proliferation and fibrosis, finally cirrhosis development could arise from chronic micro-vascular ischemia. Recently, some important confirmation of this hypothesis has been reported. In fact, in a murine experimental model of congestive hepatopathy, it was found that chronic hepatic congestion leads to sinusoidal thrombosis and strain, which in turn promote hepatic fibrosis. Furthermore, a study on a murine model of cirrhosis reported enoxaparin to reduce hepatic vascular resistance and portal pressure by having a protective role against fibrogenesis. In conclusion, the hypothesis giving a central role of micro-vascular ischemia in fibrogenesis and cirrhosis development could change the clinical scenario of chronic liver disease and have several main implications on management of various liver disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

MicroRNAs as biomarkers for graft-versus-host disease following allogeneic stem cell transplantation.

PubMed

Tomuleasa, Ciprian; Fuji, Shigeo; Cucuianu, Andrei; Kapp, Markus; Pileczki, Valentina; Petrushev, Bobe; Selicean, Sonia; Tanase, Alina; Dima, Delia; Berindan-Neagoe, Ioana; Irimie, Alexandru; Einsele, Hermann

2015-07-01

Allogeneic hematopoietic stem cell transplantation (HCT) is a well-established treatment for many malignant and non-malignant hematological disorders. As frequent complication in up to 50 % of all patients, graft-versus-host disease (GVHD) is still the main cause for morbidity and non-relapse mortality. Diagnosis of GVHD is usually done clinically, even though confirmation by pathology is often used to support the clinical findings. Effective treatment requires intensified immunosuppression as early as possible. Although several promising biomarkers have been proposed for an early diagnosis, no internationally recognized consensus has yet been established. Here, microRNAs (miRs) represent an interesting tool since miRs have been recently reported to be an important regulator of various cells, including immune cells such as T cells. Therefore, we could assume that miRs play a key role in the pathogenesis of acute GVHD, and their detection might be an interesting possibility in the early diagnosis and monitoring of acute GVHD. Recent studies additionally demonstrated the implication of miRs in the pathogenesis of acute GVHD. In this review, we aim to summarize the previous reports of miRs, focusing on the pathogenesis of acute GVHD and possible implications in diagnostic approaches.

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.

Factors to consider when reviewing and reconciling research findings: Methodological, statistical and theoretical.

PubMed

Robinson, Sally J

2017-11-07

Neuroscience is a rapidly evolving interdisciplinary field that is changing the way research is conducted and theories are developed. However, variability between studies and apparently discrepant findings may contribute to difficulties identifying commonalities that can help inform and enhance clinical practice. This article presents a framework to consider when reviewing neuropsychological studies, such that apparent discrepancies in findings may be considered in unison to provide informed theoretical understanding. For illustrative purposes, the article considers the studies of Vargha-Khadem, Salmond, Friston, Gadian, and Mishkin ( 2003 ) and Beauchamp et al. ( 2008 ), which report contrasting memory deficits during development in association with apparently similar bilateral hippocampal damage. The importance of reflecting on participant characteristics, methodological approaches, statistical analysis, and the interpretative value placed on selective test findings are discussed. Factors such as functional brain development, relationships between apparently "typical" functioning and underlying neural structures and networks, the limits of plasticity on the developing cognitive system and clinical implications are also considered. Thus, this article provides a structure that can be applied when reviewing neuropsychological studies and evaluating research inconsistencies, with consideration of the need for greater collaboration between neuroscientists and clinicians to support the development of translational research with real life implications.

Alternative caregiving figures and their role on adult attachment representations.

PubMed

Zaccagnino, Maria; Cussino, Martina; Saunders, Rachel; Jacobvitz, Deborah; Veglia, Fabio

2014-01-01

The present work represents the first Italian study investigating whether and how mothers who describe unloving experiences with both parents during childhood could become more secure as adults (termed earned-secures). The sample consisted of 94 women from northern Italy. All the subjects were administered the Adult Attachment Interview (AAI) and fill in a screening test evaluating depressive symptoms. No significative differences were found regarding depressive symptomatology across the different attachment classifications. The majority of the samples (84%) remember an important alternative support figure during childhood (before 12 years old). Earned-secures significantly differ from continuous-secure and insecure groups (F = 27.202; p ≤ 0.01) on the amount of the emotional support from the main alternative support figure and on the average amount of emotional support across alternative support figures (F = 10.44; p ≤ 0.01). The majority of alternative support figures (80%) were grandparents. A corrective emotional experience allows the subject to work through his negative childhood experiences and acquire modalities of interaction that enable him/her to function more effectively in the world. The clinical implications of this study will be discussed. Attachment theory. Clinical implications of attachment experiences. Corrective emotional experience. Copyright © 2012 John Wiley & Sons, Ltd.

Probiotic actions on diseases: implications for therapeutic treatments.

PubMed

Chiu, Yi-Heng; Lin, Shiao-Lin; Tsai, Jaw-Ji; Lin, Meei-Yn

2014-04-01

The ecology of gut microflora, which colonizes all body surfaces, has long coevolved with its hosts in a complicated fashion. Health benefits conferred by gut microflora include defense against invading pathogens, improvement of nutritional bioavailability, and development of the regional and systemic immune systems. The past decade has witnessed growing interest in the fact that the gut microflora affects the host's energy homeostasis by means of various mechanisms, including supplying nourishment from indigestible compounds, producing small biomolecules responsible for lipid profiles, and participating in the absorption, distribution, metabolism and excretion of nutrition. Much in vitro and in vivo research has indicated that aberrant gut microflora plays an important role in the pathogenesis of a wide spectrum of diseases. This is accomplished by a shift in focus, from laying an emphasis on pharmacotherapy to placing more effort on gut microflora normalization. The objectives of this review include illustrating trends in the clinical application of probiotics on diseases, as well as discussing current methodology limitations on probiotic selection. Furthermore, it is expected to shed light on the nature of probiotics, with the aim of giving greater insight into the implications for clinical use of probiotics in the treatment of diseases.

The words we work with that work on us: clinical paradigm and cumulative relational trauma.

PubMed

Heuer, Birgit

2017-11-01

This paper addresses a gap between analytic clinical theory and practice which emerges when examining the words we work with via textual and narrative research of case histories. Both subject matter and methodology fit with the remit of conceptual research in psychoanalysis, currently ranging from inductive to nomothetical approaches. Research of clinical language reveals an implicit account of human nature and the world which undergirds clinical practice. Based in the critical philosophy of the previous century, this is termed clinical paradigm. Such implicit views are induced rather than explicitly taught during analytic training, and need to be spelled out in order to become available to discourse and difference of opinion. Textual research shows these implicit pre-clinical attitudes to be inherently pessimistic and thus too similar to the views of self and others found in cumulative relational trauma. Moreover, clinical accounts tend to normalize subtly antagonistic forms of relating, recently recognised as micro-trauma. Importantly, this contravenes the agapic orientation of our theories and ethics. Paradigmatic reflection as a form of professional individuation addresses this gap. This includes a more optimistic outlook which can be traced through the philosophical implications of quantum theory. © 2017, The Society of Analytical Psychology.

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

Shifting from presumptive to test-based management of malaria - technical basis and implications for malaria control in Ghana.

PubMed

Baiden, F; Malm, K; Bart-Plange, C; Hodgson, A; Chandramohan, D; Webster, J; Owusu-Agyei, S

2014-06-01

The presumptive approach was the World Health Organisation (WHO) recommended to the management of malaria for many years and this was incorporated into syndromic guidelines such as the Integrated Management of Childhood Illnesses (IMCI). In early 2010 however, WHO issued revised treatment guidelines that call for a shift from the presumptive to the test-based approach. Practically, this implies that in all suspected cases, the diagnosis of uncomplicated malaria should be confirmed using rapid test before treatment is initiated. This revision effectively brings to an end an era of clinical practice that span several years. Its implementation has important implications for the health systems in malaria-endemic countries. On the basis of research in Ghana and other countries, and evidence from program work, the Ghana National Malaria Control Program has issued revised national treatment guidelines that call for implementation of test-based management of malaria in all cases, and across all age groups. This article reviews the evidence and the technical basis for the shift to test-based management and examines the implications for malaria control in Ghana.

Agreement Between Electronic Medical Record-based and Self-Administered Pain Numeric Rating Scale: Clinical and Research Implications

PubMed Central

Goulet, Joseph L.; Brandt, Cynthia; Crystal, Stephen; Fiellin, David A.; Gibert, Cynthia; Gordon, Adam J.; Kerns, Robert D.; Maisto, Stephen; Justice, Amy C.

2012-01-01

Background Pain screening may improve the quality of care by identifying patients in need of further assessment and management. Many healthcare systems use the numeric rating scale (NRS) for pain screening, and record the score in the patients’ electronic medical record (EMR). Objective Determine level of agreement between EMR and patient survey NRS, and whether discrepancies vary by demographic and clinical characteristics. Methods We linked survey data from a sample of Veterans receiving care in eight Veterans Affairs (VA) medical facilities, to EMR data including an NRS collected on the day of the survey in order to compare responses to the NRS question from these two sources. We assessed correlation, agreement on clinical cut-points (e.g. severe), and, using the survey as the gold standard, whether patient characteristics were associated with a discrepancy on moderate-severe pain. Results A total of 1,643 participants had a survey and EMR NRS score on the same day. The correlation was 0.56 (95% CI 0.52/0.59), but the mean EMR score was significantly lower than the survey score (1.72 vs. 2.79; p<0.0001). Agreement was moderate (kappa=0.35). Characteristics associated with a increased odds of a discrepancy included: diabetes (adjusted odds ratio (AOR)=1.48), post traumatic stress disorder (AOR=1.59), major depressive disorder (AOR=1.81), other race vs. white (AOR=2.29), and facility in which care was received. Conclusions The underestimation of pain using EMR data, especially clinically actionable levels of pain, has important clinical and research implications. Improving the quality of pain care may require better screening. PMID:23222528

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.

Prognostic implications of epicardial fat volume quantification in acute pericarditis.

PubMed

Lazaros, George; Antonopoulos, Alexios S; Oikonomou, Evangelos K; Vasileiou, Panagiotis; Oikonomou, Evangelos; Stroumpouli, Evangelia; Karavidas, Apostolos; Antoniades, Charalambos; Tousoulis, Dimitris

2017-02-01

The pathophysiology of acute pericarditis remains largely unknown, and biomarkers are needed to identify patients susceptible to complications. As adipose tissue has a pivotal role in cardiovascular disease pathogenesis, we hypothesized that quantification of epicardial fat volume (EFV) provides prognostic information in patients with acute pericarditis. Fifty (n = 50) patients with first diagnosis of acute pericarditis were enrolled in this study. Patients underwent a cardiac computerized tomography (CT) scan to quantify EFV on a dedicated workstation. Patients were followed up in hospital for atrial fibrillation (AF) development and up to 18 months for the composite clinical endpoint of development of constrictive, recurrent or incessant pericarditis or poor response to nonsteroidal anti-inflammatory drugs. Patients presenting with chest pain had lower EFV vs. patients without chest pain (167·2 ± 21·7 vs. 105·1 ± 11·1 cm 3 , respectively, P < 0·01); EFV (but not body mass index) was strongly positively correlated with pericardial effusion size (r = 0·395, P = 0·007) and associated with in-hospital AF. At follow-up, patients that reached the composite clinical endpoint had lower EFV (P < 0·05). After adjustment for age, EFV was associated with lower odds ratio for the composite clinical endpoint point of poor response to NSAIDs or the development of constrictive, recurrent or incessant pericarditis during follow-up (per 20 cm 3 increase in EFV: OR = 0·802 [0·656-0·981], P < 0·05). We report for the first time a significant association of EFV with the clinical features and the outcome of patients with acute pericarditis. Measurement of EFV by CT may have important prognostic implications in these patients. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

Evidenced-based review of clinical studies on periodontics.

PubMed

2009-08-01

Periodontal diseases have several implications for the practice of endodontics. First, advanced periodontitis often has direct implications for the long-term prognosis of the case and requires careful evaluation and coordinated treatment of both the periodontic and endodontic diseases. Second, the potential for functional interactions between odontogenic pathoses and marginal periodontitis requires careful collection of clinical observations and monitoring the outcome of various treatments. In this section, we provide an analysis of recent clinical studies in this area.

Biomarkers of PTSD: military applications and considerations.

PubMed

Lehrner, Amy; Yehuda, Rachel

2014-01-01

Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

A review of issues and concerns of family members of adult burn survivors.

PubMed

Sundara, Diana C

2011-01-01

The purpose of this review is to synthesize what is known about the issues and concerns of families of adult burn survivors from research and clinical articles written between 1973 and 2009. Electronic database searching, ancestry searching, and electronic hand searching were performed to identify relevant articles. Seventeen research studies and 14 clinical articles were identified. Families are often in crisis immediately after the injury. This crisis involves strong emotions, some of which may persist over time. Throughout the course of hospitalization, family issues include worries about their loved one's physical appearance, logistical concerns, and the transition to home. For partners, role changes and sexual concerns may be of particular importance. Extended family, friends, the burn team, and other families affected by a burn injury are important sources of support for family members. Few studies have been conducted beyond the time of hospitalization. Clinical articles have identified issues not present in the research literature. Further research is needed that focuses more closely on families and their experiences both in and out of the hospital. Implications for burn care providers based on the findings of this review are discussed.

EXTRAHEPATIC TOXICITY OF ACETAMINOPHEN: CRITICAL EVALUATION OF THE EVIDENCE AND PROPOSED MECHANISMS

PubMed Central

Kennon-McGill, Stefanie; McGill, Mitchell R.

2017-01-01

Research on acetaminophen (APAP) toxicity over the last several decades has focused on the pathophysiology of liver injury, but increasing attention is being paid to other known and possible adverse effects. It has been known for decades that APAP causes acute kidney injury, but confusion exists regarding prevalence, and the mechanisms have not been well investigated. More recently, a number of experimental, clinical and epidemiological studies have reported evidence for pulmonary, endocrine, neurological and neurodevelopmental toxicity, but the quality of evidence from those studies varies. It is important to consider these data due to implications for regulation and clinical practice. Here, we review the evidence and proposed mechanisms for extrahepatic adverse effects of APAP and weigh weaknesses and strengths in the data. We consider results from clinical, epidemiological and experimental research. Our goal is to determine the strength of claims regarding extrahepatic toxicity of APAP and to identify areas of need for future research. It is especially important to view claims of developmental effects of antenatal APAP exposure with a critical eye because APAP is currently the only over-the-counter medication recommended for pregnant women to self-treat pain and fever. PMID:29457141

Climate Change Effects on Respiratory Health: Implications for Nursing.

PubMed

George, Maureen; Bruzzese, Jean-Marie; Matura, Lea Ann

2017-11-01

Greenhouse gases are driving climate change. This article explores the adverse health effects of climate change on a particularly vulnerable population: children and adults with respiratory conditions. This review provides a general overview of the effects of increasing temperatures, extreme weather, desertification, and flooding on asthma, chronic obstructive lung disease, and respiratory infections. We offer suggestions for future research to better understand climate change hazards, policies to support prevention and mitigation efforts targeting climate change, and clinical actions to reduce individual risk. Climate change produces a number of changes to the natural and built environments that may potentially increase respiratory disease prevalence, morbidity, and mortality. Nurses might consider focusing their research efforts on reducing the effects of greenhouse gases and in directing policy to mitigate the harmful effects of climate change. Nurses can also continue to direct educational and clinical actions to reduce risks for all populations, but most importantly, for our most vulnerable groups. While advancements have been made in understanding the impact of climate change on respiratory health, nurses can play an important role in reducing the deleterious effects of climate change. This will require a multipronged approach of research, policy, and clinical action. © 2017 Sigma Theta Tau International.

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.

The relationship between maternal self-efficacy and parenting practices: implications for parent training.

PubMed

Sanders, M R; Woolley, M L

2005-01-01

The present study examined the relationship between maternal self-efficacy, dysfunctional discipline practices and child conduct problems. Specifically, three levels of self-efficacy, global, domain and task-specific self-efficacy, were assessed in mothers of 2- to 8-year-old children with conduct problems (clinic group, n=45) and non-clinic mothers from the community (non-clinic group, n=79). Measures of global, domain and task-specific self-efficacy were completed by mothers. Clinic mothers reported significantly lower self-efficacy than non-clinic mothers for all but one of the parenting tasks assessed. Both groups of mothers reported lowest self-efficacy for similar parenting tasks. In the sample as a whole self-efficacy measures were significant predictors of maternal discipline style after controlling for other parent, child and risk factors. Of the self-efficacy variables behavioural self-efficacy was the best predictor of mothers discipline style. The findings support the importance of developing parenting strategies that enable parents to generalize their parenting skills to a diverse range of diverse parenting contexts both in the home and in the community.

Relevance of MICA and other non-HLA antibodies in clinical transplantation.

PubMed

Sumitran-Holgersson, Suchitra

2008-10-01

The clinical importance of HLA-specific antibodies for organ allograft outcome is well established. In the past few years, there has been an increasing interest in non-HLA antigens as targets of injury in organ transplant recipients. This increased interest has been spurred by the fact that HLA-identical kidney transplants also undergo immunological rejections. Polymorphisms within non-HLA genes associated with evoking an immune response to alloantigens are currently being studied for their association with transplant outcome. Non-HLA antigens, such as the polymorphic MHC class I-related chain A (MICA), expressed on endothelial cells have been implicated in the pathogenesis of hyperacute, acute and chronic organ allograft rejections. Use of endothelial cells as targets may clarify the specificities of other clinically relevant non-HLA antibodies in graft rejections. This review summarizes past and current knowledge of the clinical importance and specificities of non-HLA antibodies, and mechanisms by which these antibodies may contribute to graft destruction in clinical transplantation. The aims of current research into the role of non-HLA antigens and their genetics in predicting outcome are to develop an improved insight into the basic science of transplantation and to develop a risk or prognostic index for use in the clinical setting. Non-HLA antibody responses are receiving increasing interest in acute and chronic rejection and specificity, affinity, and pathogenicity need to be investigated to estimate their contribution. Undoubtedly, this will continue to be an area of interest in terms of fully understanding the role of non-HLA antigens as targets of immune-mediated injury and the potential for clinical intervention.

Is undifferentiated spondyloarthritis a discrete entity? A debate.

PubMed

Deodhar, Atul; Miossec, Pierre; Baraliakos, Xenofon

2018-01-01

The concept of undifferentiated spondyloarthritis has been introduced recently to describe a clinical setting where the classical features of spondyloarthritis (SpA) are not fully present. Whether this is a discrete entity was the basis of a debate during the 4th International Congress on Controversies in Rheumatology & Autoimmunity held in Bologna, Italy 9-11 March 2017. The pro and con aspects of the debate are presented. The implications of the debate are important ranging from diagnostic aspects to consequences for the society and the payers. Copyright © 2017 Elsevier B.V. All rights reserved.

Cerebellar mutism syndrome and its relation to cerebellar cognitive and affective function: Review of the literature

PubMed Central

Yildiz, Ozlem; Kabatas, Serdar; Yilmaz, Cem; Altinors, Nur; Agaoglu, Belma

2010-01-01

Tumors of the cerebellum and brainstem account for half of all brain tumors in children. The realization that cerebellar lesions produce clinically relevant intellectual disability makes it important to determine whether neuropsychological abnormalities occur in long-term survivors of pediatric cerebellar tumors. Little is known about the neurobehavioral sequale resulting specifically from the resection of these tumors in this population. We therefore reviewed neuropsychological findings associated with postoperative cerebellar mutism syndrome and discuss the further implications for cerebellar cognitive function. PMID:20436742

Bridging the gap from values to actions: a family systems framework for family-centered AAC services.

PubMed

Mandak, Kelsey; O'Neill, Tara; Light, Janice; Fosco, Gregory M

2017-03-01

Despite the growing recognition of the importance of family involvement in augmentative and alternative communication (AAC) intervention, little guidance exists on how professionals can establish successful collaborative relationships with families. In this paper, we discuss family systems theory and ecological systems theory as a framework to guide family-centered AAC practice, review family-focused research in AAC, consider how AAC may impact the family system, and provide examples of the clinical implications of using the proposed family systems framework to improve family-centered AAC practice.

The kappa-opiate receptor impacts the pathophysiology and behavior of substance use.

PubMed

Mysels, David; Sullivan, Maria A

2009-01-01

There is increasing evidence that the kappa-opiate receptor, in addition to the mu-opiate receptor, plays an important role in substance use pathophysiology and behavior. As dopamine activity is upregulated through chronic substance use, kappa receptor activity, mediated through the peptide dynorphin, is upregulated in parallel. Dynorphin causes dysphoria and decreased locomotion, and the upregulation of its activity on the kappa receptor likely dampens the excitation caused by increased dopaminergic activity. This feedback mechanism may have significant clinical implications for treating drug dependent patients in various stages of their pathology.

Beyond positivism: Understanding and addressing childhood obesity disparities through a Critical Theory perspective.

PubMed

Schroeder, Krista; Kulage, Kristine M; Lucero, Robert

2015-10-01

We apply Critical Theory to examine menu labeling with the aim of uncovering important implications for nursing practice, research, and policy. Our critical analysis uncovers barriers to menu labeling's effectiveness, particularly for vulnerable populations. Nurses must work to minimize the impact of these barriers and optimize the effectiveness of menu labeling, in order to strengthen the fight against obesity. We suggest changes, guided by this critical analysis, which can be implemented by nurses working in clinical practice, research, and policy. © 2015, Wiley Periodicals, Inc.

Reflections on Self-Reflection: Contemplating Flawed Self-Judgments in the Clinic, Classroom, and Office Cubicle.

PubMed

Dunning, David; Heath, Chip; Suls, Jerry M

2018-03-01

We reflect back on our 2004 monograph reviewing the implications of faulty self-judgment for health, education, and the workplace. The review proved popular, no doubt because the importance of accurate self-assessment is best reflected in just how broad the literature is that touches on this topic. We discuss opportunities and challenges to be found in the future study of self-judgment accuracy and error, and suggest that designing interventions aimed at improving self-judgments may prove to be a worthwhile but complex and nuanced task.

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

Sleep: important considerations for the prevention of cardiovascular disease.

PubMed

Grandner, Michael A; Alfonso-Miller, Pamela; Fernandez-Mendoza, Julio; Shetty, Safal; Shenoy, Sundeep; Combs, Daniel

2016-09-01

Sleep plays many roles in maintenance of cardiovascular health. This review summarizes the literature across several areas of sleep and sleep disorders in relation to cardiometabolic disease risk factors. Insufficient sleep duration is prevalent in the population and is associated with weight gain and obesity, inflammation, cardiovascular disease, diabetes, and mortality. Insomnia is also highly present and represents an important risk factor for cardiovascular disease, especially when accompanied by short sleep duration. Sleep apnea is a well-characterized risk factor for cardiometabolic disease and cardiovascular mortality. Other issues are relevant as well. For example, sleep disorders in pediatric populations may convey cardiovascular risks. Also, sleep may play an important role in cardiovascular health disparities. Sleep and sleep disorders are implicated in cardiometabolic disease risk. This review addresses these and other issues, concluding with recommendations for research and clinical practice.

Changes in Neuropsychological Status during the Initial Phase of Abstinence in Alcohol Use Disorder: Neurocognitive Impairment and Implications for Clinical Care.

PubMed

Mulhauser, Kyler; Weinstock, Jeremiah; Ruppert, Phillip; Benware, Jeffrey

2018-05-12

Neuropsychological deficits are common in individuals with alcohol use disorder (AUD) and impact daily functioning and AUD treatment outcomes. Longitudinal studies demonstrate that extended abstinence improves neuropsychological functioning. The effects of short-term abstinence are less clear. This study examined changes in neuropsychological functioning after acute detoxification over a 10-day period at the beginning of residential AUD treatment. Notably, this study evaluated cognitive functioning according to diagnostic classifications for neurocognitive disorder according to DSM-5. Using a within-subjects design, neuropsychological functioning of participants (N = 28) undergoing a 14-day residential AUD treatment program was assessed at two time points over 10 days (i.e., treatment entry, prior to treatment discharge). Tests of immediate memory, visuospatial abilities, attention, language abilities, delayed memory, and executive functioning were administered. After completing acute detoxification, almost all participants (93%) were clinically impaired in at least one of the five cognitive domains at residential treatment entry, with one third of the sample impaired on ≥3 domains. Ten days later, 71% remained clinically impaired in at least one of five cognitive domains, with 29% of the sample impaired on ≥3 domains. Significant improvement over the 10-day period was observed for immediate memory, visuospatial abilities, and overall cognitive functioning. Clinical significance of these changes is also reported. Conclusions/Importance: The results from this study help to characterize cognitive functioning in terms of neurocognitive impairment. A brief period of abstinence begins to ameliorate neuropsychological deficits, but many individuals remain cognitively impaired throughout treatment. Implications for treatment are discussed.

State of the Art in HIV Drug Resistance: Science and Technology Knowledge Gap.

PubMed

Boucher, Charles A; Bobkova, Marina R; Geretti, Anna Maria; Hung, Chien-Ching; Kaiser, Rolf; Marcelin, Anne-Geneviève; Streinu-Cercel, Adrian; van Wyk, Jean; Dorr, Pat; Vandamme, Anne-Mieke

2018-01-01

Resistance to antiretroviral therapy (ART) threatens the efficacy of human immunodeficiency virus type 1 (HIV-1) treatment. We present a review of knowledge gaps in the science and technologies of acquired HIV-1 drug resistance (HIVDR) in an effort to facilitate research, scientific exchange, and progress in clinical management. The expert authorship of this review convened to identify data gaps that exist in the field of HIVDR and discuss their clinical implications. A subsequent literature review of trials and current practices was carried out to provide supporting evidence. Several gaps were identified across HIVDR science and technology. A summary of the major gaps is presented, with an expert discussion of their implications within the context of the wider field. Crucial to optimizing the use of ART will be improved understanding of protease inhibitors and, in particular, integrase strand transfer inhibitors (INSTI) in the context of HIVDR. Limited experience with INSTI represents an important knowledge gap in HIV resistance science. Utilizing such knowledge in a clinical setting relies on accurate testing and analysis of resistance-associated mutations. As next-generation sequencing becomes more widely available, a gap in the interpretation of data is the lack of a defined, clinically relevant threshold of minority variants. Further research will provide evidence on where such thresholds lie and how they can be most effectively applied. Expert discussion identified a series of gaps in our knowledge of HIVDR. Addressing prefsuch gaps through further research and characterization will facilitate the optimal use of ART therapies and technologies.

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.

Spectators & spectacles: nurses, midwives and visuality.

PubMed

Barnard, Alan G; Sinclair, Marlene

2006-09-01

In this paper we reflect on how linear perspective vision influences the practice of nurses and midwives and to advance understanding of clinical practice in technologically intensive environments through examination of drawings by nurses and midwives and through critical analysis. There is increasing emphasis on vision in Western culture, and both nurses and midwives spend a great deal of time observing their clinical environment(s). Healthcare practitioners work increasingly in image-based realities and nurses rely on visual skills. Vision and visual representation are central to our practice and are important to examine because we look often at technology to assess people and care. The world in which we practise is one of meaning(s). Technological development is transformative in nature and produces changes that alter the way(s) we give care. Amongst all this change, it is unclear how we practise in environments characterized by increasing technology and it is unknown how nursing and midwifery practice alter as a result. Simple drawings included in this paper highlight an important and shared experience of clinical practice(s). They emphasize the importance and scope of the visual sense and expose practitioner behaviour that has enormous implications for current and future professional development and person-focussed care provision. Experiences described in this paper require further examination and highlight substantial changes to nurse-patient relationships, health care and the way we practise.

Status of imported malaria in a control zone of the United Arab Emirates bordering an area of unstable malaria.

PubMed

Dar, F K; Bayoumi, R; al Karmi, T; Shalabi, A; Beidas, F; Hussein, M M

1993-01-01

A concerted malaria eradication programme in the United Arab Emirates has reduced local transmission to only a very few small foci in the country. The Al Ain district is now a consolidation zone. However, transmission across the undemarcated border with Oman continues. Malaria imported by the large immigrant work force from major disease endemic areas remains a large burden. An added threat is the appearance of chloroquine-resistant Plasmodium falciparum principally from Sudan and Pakistan but increasingly amongst Omani cases seen in the hospitals and clinics in Al Ain. The implications of re-introduction of malaria and the establishment of chloroquine resistance, particularly for non-immune residents and visitors, are emphasized.

Biomechanical properties of the spinal cord: implications for tissue engineering and clinical translation.

PubMed

Bartlett, Richard D; Choi, David; Phillips, James B

2016-10-01

Spinal cord injury is a severely debilitating condition which can leave individuals paralyzed and suffering from autonomic dysfunction. Regenerative medicine may offer a promising solution to this problem. Previous research has focused primarily on exploring the cellular and biological aspects of the spinal cord, yet relatively little remains known about the biomechanical properties of spinal cord tissue. Given that a number of regenerative strategies aim to deliver cells and materials in the form of tissue-engineered therapies, understanding the biomechanical properties of host spinal cord tissue is important. We review the relevant biomechanical properties of spinal cord tissue and provide the baseline knowledge required to apply these important physical concepts to spinal cord tissue engineering.

HIV testing updates and challenges: when regulatory caution and public health imperatives collide.

PubMed

Branson, Bernard M

2015-03-01

Numerous improvements in HIV testing technology led recently to the first revision of recommendations for diagnostic laboratory testing in the USA in 25 years. Developments in HIV testing continue to produce tests that identify HIV infection earlier with faster turnaround times for test results. These play an important role in identifying HIV infection during the highly infectious acute phase, which has implication for both patient management and public health interventions to control the spread of HIV. Access to these developments, however, is often delayed by the regulatory apparatus for approval and oversight of HIV testing in the USA. This article summarizes recent developments in HIV diagnostic testing technology, outlines their implications for clinical management and public health, describes current systems of regulatory oversight for HIV testing in the USA, and proposes alternatives that could expedite access to improved tests as they become available.

Stress fracture risk factors in female football players and their clinical implications

PubMed Central

Warden, Stuart J; Creaby, Mark W; Bryant, Adam L; Crossley, Kay M

2007-01-01

A stress fracture represents the inability of the skeleton to withstand repetitive bouts of mechanical loading, which results in structural fatigue, and resultant signs and symptoms of localised pain and tenderness. Reports of stress fractures in female football players are not prevalent; however, they are probably under‐reported and their importance lies in the morbidity that they cause in terms of time lost from participation. By considering risk factors for stress fractures in female football players it may be possible to reduce the impact of these troublesome injuries. Risk factors for stress fractures in female football players include intrinsic risk factors such as gender, endocrine, nutritional, physical fitness and neuromusculoskeletal factors, as well as extrinsic risk factors such as training programme, equipment and environmental factors. This paper discusses these risk factors and their implications in terms of developing prevention and management strategies for stress fractures in female football players. PMID:17584950

Stress fracture risk factors in female football players and their clinical implications.

PubMed

Warden, Stuart J; Creaby, Mark W; Bryant, Adam L; Crossley, Kay M

2007-08-01

A stress fracture represents the inability of the skeleton to withstand repetitive bouts of mechanical loading, which results in structural fatigue, and resultant signs and symptoms of localised pain and tenderness. Reports of stress fractures in female football players are not prevalent; however, they are probably under-reported and their importance lies in the morbidity that they cause in terms of time lost from participation. By considering risk factors for stress fractures in female football players it may be possible to reduce the impact of these troublesome injuries. Risk factors for stress fractures in female football players include intrinsic risk factors such as gender, endocrine, nutritional, physical fitness and neuromusculoskeletal factors, as well as extrinsic risk factors such as training programme, equipment and environmental factors. This paper discusses these risk factors and their implications in terms of developing prevention and management strategies for stress fractures in female football players.

Acne vulgaris, probiotics and the gut-brain-skin axis - back to the future?

PubMed

Bowe, Whitney P; Logan, Alan C

2011-01-31

Over 70 years have passed since dermatologists John H. Stokes and Donald M. Pillsbury first proposed a gastrointestinal mechanism for the overlap between depression, anxiety and skin conditions such as acne. Stokes and Pillsbury hypothesized that emotional states might alter the normal intestinal microflora, increase intestinal permeability and contribute to systemic inflammation. Among the remedies advocated by Stokes and Pillsbury were Lactobacillus acidophilus cultures. Many aspects of this gut-brain-skin unifying theory have recently been validated. The ability of the gut microbiota and oral probiotics to influence systemic inflammation, oxidative stress, glycemic control, tissue lipid content and even mood itself, may have important implications in acne. The intestinal microflora may also provide a twist to the developing diet and acne research. Here we provide a historical perspective to the contemporary investigations and clinical implications of the gut-brain-skin connection in acne.

Acne vulgaris, probiotics and the gut-brain-skin axis - back to the future?

PubMed Central

2011-01-01

Over 70 years have passed since dermatologists John H. Stokes and Donald M. Pillsbury first proposed a gastrointestinal mechanism for the overlap between depression, anxiety and skin conditions such as acne. Stokes and Pillsbury hypothesized that emotional states might alter the normal intestinal microflora, increase intestinal permeability and contribute to systemic inflammation. Among the remedies advocated by Stokes and Pillsbury were Lactobacillus acidophilus cultures. Many aspects of this gut-brain-skin unifying theory have recently been validated. The ability of the gut microbiota and oral probiotics to influence systemic inflammation, oxidative stress, glycemic control, tissue lipid content and even mood itself, may have important implications in acne. The intestinal microflora may also provide a twist to the developing diet and acne research. Here we provide a historical perspective to the contemporary investigations and clinical implications of the gut-brain-skin connection in acne. PMID:21281494

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

Blast TBI Models, Neuropathology, and Implications for Seizure Risk

PubMed Central

Kovacs, S. Krisztian; Leonessa, Fabio; Ling, Geoffrey S. F.

2014-01-01

Traumatic brain injury (TBI) due to explosive blast exposure is a leading combat casualty. It is also implicated as a key contributor to war related mental health diseases. A clinically important consequence of all types of TBI is a high risk for development of seizures and epilepsy. Seizures have been reported in patients who have suffered blast injuries in the Global War on Terror but the exact prevalence is unknown. The occurrence of seizures supports the contention that explosive blast leads to both cellular and structural brain pathology. Unfortunately, the exact mechanism by which explosions cause brain injury is unclear, which complicates development of meaningful therapies and mitigation strategies. To help improve understanding, detailed neuropathological analysis is needed. For this, histopathological techniques are extremely valuable and indispensable. In the following we will review the pathological results, including those from immunohistochemical and special staining approaches, from recent preclinical explosive blast studies. PMID:24782820

Prescription drug abuse: problem, policies, and implications.

PubMed

Phillips, Janice

2013-01-01

This article provides an overview on prescription drug abuse and highlights a number of related legislative bills introduced during the 112th Congress in response to this growing epidemic. Prescription drug abuse has emerged as the nation's fastest growing drug problem. Although prescription drugs have been used effectively and appropriately for decades, deaths from prescription pain medicine in particular have reached epidemic proportions. Bills related to prescription drug abuse introduced during the 112th Congress focus on strengthening provider and consumer education, tracking and monitoring prescription drug abuse, improving data collection on drug overdose fatalities, combating fraud and abuse in Medicare and Medicaid programs, reclassifying drugs to make them more difficult to prescribe and obtain, and enforcing stricter penalties for individuals who operate scam pain clinics and sell pain pills illegitimately. This article underscores the importance of a multifaceted approach to combating prescription drug abuse and concludes with implications for nursing. Copyright © 2013. Published by Mosby, Inc.

Sexual abuse of children: an update.

PubMed Central

Finkel, K C

1987-01-01

An increasing number of studies in the past decade have shown that sexual abuse of children is disturbingly common. The author reviews some of the more recent knowledge about the problem, with particular reference to medical implications. The incidence and distribution of the problem and the relative importance of the medical examination are reviewed, and the diagnostic significance of clinical presentations such as vulvovaginitis, recurrent urinary tract infection and masturbation is evaluated. The agents responsible for sexually transmitted diseases in abused children are reviewed. Many crucial psychosocial issues are raised in the evaluation and management of sexual abuse. The author discusses some aspects of abuse that are hard to confront, such as the possible pleasure of the child and the nonoffending role of the mother in cases of incest. Information from sources other than the medical literature on the characteristics of abusers, therapy and prevention is reviewed. The medical implications of the Badgley Report are also discussed. PMID:3801988

An integrative review of separation in the context of victimization: consequences and implications for women.

PubMed

Walker, Robert; Logan, T K; Jordan, Carol E; Campbell, Jacquelyn C

2004-04-01

Given the number of divorces that occur each year as well as the high rates of intimate partner violence, it is critical that divorce/separation and victimization be considered in research and in clinical practice with women. However, the separation/divorce research and victimization research has often been conducted independently, with limited attention to integration. The integration of these two domains is critically important in facilitating the understanding of these issues for women. This article has 5 main purposes: (a) to review the research on the general consequences of separation; (b) to review the research on the consequences of separation when children are involved; (c) to review the research on the consequences of victimization; (d) to integrate the separation and victimization research to examine separation in the context of victimization; and (e) to discuss the implications of separation in the context of victimization for practice and research.

Innate immunity in HIV infection and implications for vaccine design: a summary of the workshop held at the National Institute of Allergy and Infectious Diseases, Bethesda on February 25-26, 2010.

PubMed

Bansal, Geetha P; Leitner, Wolfgang W

2010-12-06

The search for an effective HIV vaccine continues to be a challenge. Several candidates have been tested in preclinical protocols, and a few have been tested in clinical trials without resounding success. It is unclear why vaccine approaches to control HIV infection have been unsuccessful, but opportunities to dissect the causes for the failure have surfaced from recent work on the virology, immunology and pathogenesis of HIV and from analysis of vaccine studies. The significance of the innate immune system in HIV infection may provide new paths to discover effective approaches. This report summarizes a workshop held to discuss the role of selected aspects of innate immunity to viral infections and successful vaccines that may have important implications for designing effective HIV vaccines. Copyright © 2010. Published by Elsevier Ltd.. All rights reserved.

Memantine and Kynurenic Acid: Current Neuropharmacological Aspects

PubMed Central

Majláth, Zsófia; Török, Nóra; Toldi, József; Vécsei, László

2016-01-01

Glutamatergic neurotransmission, of special importance in the human brain, is implicated in key brain functions such as synaptic plasticity and memory. The excessive activation of N-methyl- D-aspartate (NMDA) receptors may result in excitotoxic neuronal damage; this process has been implicated in the pathomechanism of different neurodegenerative disorders, such as Alzheimer’s disease (AD). Memantine is an uncompetitive antagonist of NMDA receptors with a favorable pharmacokinetic profile, and is therefore clinically well tolerated. Memantine is approved for the treatment of AD, but may additionally be beneficial for other dementia forms and pain conditions. Kynurenic acid (KYNA) is an endogenous antagonist of NMDA receptors which has been demonstrated under experimental conditions to be neuroprotective. The development of a well-tolerated NMDA antagonist may offer a novel therapeutic option for the treatment of neurodegenerative disease and pain syndromes. KYNA may be a valuable candidate for future drug development. PMID:26564141