Clinical Implementation of Pharmacogenomics for Personalized Precision Medicine: Barriers and Solutions.

PubMed

Klein, Michelle E; Parvez, Md Masud; Shin, Jae-Gook

2017-09-01

Clinical implementation of pharmacogenomics (PGx) leads to personalized medicine, which improves the efficacy, safety, and cost-effectiveness of treatments. Although PGx-based research has been conducted for more than a decade, several barriers have slowed down its widespread implementation in clinical practice. Globally, there is an imbalance in programs and solutions required to empower the clinical implementation of PGx between countries. Therefore, we aimed to review these issues comprehensively, determine the major barriers, and find the best solutions. Through an extensive review of ongoing clinical implementation programs, scientific, educational, ethical, legal, and social issues, information technology, and reimbursement were identified as the key barriers. The pace of global implementation of genomic medicine coincided with the resource limitations of each country. The key solutions identified for the earlier mentioned barriers are as follows: building of secure and suitable information technology infrastructure with integrated clinical decision support systems along with increasing PGx evidence, more regulations, reimbursement strategies for stakeholder's acceptance, incorporation of PGx education in all institutions and clinics, and PGx promotion to all health care professionals and patients. In conclusion, this review will be helpful for the better understanding of common barriers and solutions pertaining to the clinical application of PGx. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

ROC curves in clinical chemistry: uses, misuses, and possible solutions.

PubMed

Obuchowski, Nancy A; Lieber, Michael L; Wians, Frank H

2004-07-01

ROC curves have become the standard for describing and comparing the accuracy of diagnostic tests. Not surprisingly, ROC curves are used often by clinical chemists. Our aims were to observe how the accuracy of clinical laboratory diagnostic tests is assessed, compared, and reported in the literature; to identify common problems with the use of ROC curves; and to offer some possible solutions. We reviewed every original work using ROC curves and published in Clinical Chemistry in 2001 or 2002. For each article we recorded phase of the research, prospective or retrospective design, sample size, presence/absence of confidence intervals (CIs), nature of the statistical analysis, and major analysis problems. Of 58 articles, 31% were phase I (exploratory), 50% were phase II (challenge), and 19% were phase III (advanced) studies. The studies increased in sample size from phase I to III and showed a progression in the use of prospective designs. Most phase I studies were powered to assess diagnostic tests with ROC areas >/=0.70. Thirty-eight percent of studies failed to include CIs for diagnostic test accuracy or the CIs were constructed inappropriately. Thirty-three percent of studies provided insufficient analysis for comparing diagnostic tests. Other problems included dichotomization of the gold standard scale and inappropriate analysis of the equivalence of two diagnostic tests. We identify available software and make some suggestions for sample size determination, testing for equivalence in diagnostic accuracy, and alternatives to a dichotomous classification of a continuous-scale gold standard. More methodologic research is needed in areas specific to clinical chemistry.

Development of a solution adaptive unstructured scheme for quasi-3D inviscid flows through advanced turbomachinery cascades

NASA Technical Reports Server (NTRS)

Usab, William J., Jr.; Jiang, Yi-Tsann

1991-01-01

The objective of the present research is to develop a general solution adaptive scheme for the accurate prediction of inviscid quasi-three-dimensional flow in advanced compressor and turbine designs. The adaptive solution scheme combines an explicit finite-volume time-marching scheme for unstructured triangular meshes and an advancing front triangular mesh scheme with a remeshing procedure for adapting the mesh as the solution evolves. The unstructured flow solver has been tested on a series of two-dimensional airfoil configurations including a three-element analytic test case presented here. Mesh adapted quasi-three-dimensional Euler solutions are presented for three spanwise stations of the NASA rotor 67 transonic fan. Computed solutions are compared with available experimental data.

Personalizing Drug Selection Using Advanced Clinical Decision Support

PubMed Central

Pestian, John; Spencer, Malik; Matykiewicz, Pawel; Zhang, Kejian; Vinks, Alexander A.; Glauser, Tracy

2009-01-01

This article describes the process of developing an advanced pharmacogenetics clinical decision support at one of the United States’ leading pediatric academic medical centers. This system, called CHRISTINE, combines clinical and genetic data to identify the optimal drug therapy when treating patients with epilepsy or Attention Deficit Hyperactivity Disorder. In the discussion a description of clinical decision support systems is provided, along with an overview of neurocognitive computing and how it is applied in this setting. PMID:19898682

The Path to Advanced Practice Licensure for Clinical Nurse Specialists in Washington State.

PubMed

Schoonover, Heather

The aim of this study was to provide a review of the history and process to obtaining advanced practice licensure for clinical nurse specialists in Washington State. Before 2016, Washington State licensed certified nurse practitioners, certified nurse midwives, and certified nurse anesthetists under the designation of an advanced registered nurse practitioner; however, the state did not recognize clinical nurse specialists as advanced practice nurses. The work to drive the rule change began in 2007. The Washington Affiliate of the National Association of Clinical Nurse Specialists used the Power Elite Theory to guide advocacy activities, building coalitions and support for the desired rule changes. On January 8, 2016, the Washington State Nursing Care Quality Assurance Commission voted to amend the state's advanced practice rules, including clinical nurse specialists in the designation of an advanced practice nurse. Since the rule revision, clinical nurse specialists in Washington State have been granted advanced registered nurse practitioner licenses. Driving changes in state regulatory rules requires diligent advocacy, partnership, and a deep understanding of the state's rule-making processes. To be successful in changing rules, clinical nurse specialists must build strong partnerships with key influencers and understand the steps in practice required to make the desired changes.

CE: Original Research: Creating an Evidence-Based Progression for Clinical Advancement Programs.

PubMed

Burke, Kathleen G; Johnson, Tonya; Sites, Christine; Barnsteiner, Jane

2017-05-01

: Background: The Institute of Medicine (IOM) and the Quality and Safety Education for Nurses (QSEN) project have identified six nursing competencies and supported their integration into undergraduate and graduate nursing curricula nationwide. But integration of those competencies into clinical practice has been limited, and evidence for the progression of competency proficiency within clinical advancement programs is scant. Using an evidence-based approach and building on the competencies identified by the IOM and QSEN, a team of experts at an academic health system developed eight competency domains and 186 related knowledge, skills, and attitudes (KSAs) for professional nursing practice. The aim of our study was to validate the eight identified competencies and 186 related KSAs and determine their developmental progression within a clinical advancement program. Using the Delphi technique, nursing leadership validated the newly identified competency domains and KSAs as essential to practice. Clinical experts from 13 Magnet-designated hospitals with clinical advancement programs then participated in Delphi rounds aimed at reaching consensus on the developmental progression of the 186 KSAs through four levels of clinical advancement. Two Delphi rounds resulted in consensus by the expert participants. All eight competency domains were determined to be essential at all four levels of clinical practice. At the novice level of practice, the experts identified a greater number of KSAs in the domains of safety and patient- and family-centered care. At more advanced practice levels, the experts identified a greater number of KSAs in the domains of professionalism, teamwork, technology and informatics, and continuous quality improvement. Incorporating the eight competency domains and the 186 KSAs into a framework for clinical advancement programs will likely result in more clearly defined role expectations; enhance accountability; and elevate and promote nursing practice

Personhood, patienthood, and clinical practice: reassessing advance directives.

PubMed

Rich, B A

1998-09-01

This article considers 2 major critiques of advance directives and offers a defense to each of them. The 1st critique is philosophical in nature and maintains that the moral authority of an advance directive is undercut by a failure of personal identity to survive the loss of decisional capacity. The response in this article is that this critique relies on a flawed and disfavored concept of persons and their persistence over time. The 2nd critique, pragmatic in nature, argues that advance directives cannot be authoritative because the requisite elements of an informed consent to or refusal of treatment are rarely present, and many such instruments are ambiguous. The author argues that if the creation of advance directives, as a form of advance care planning, is made an integral aspect of clinical practice, many more patients will elect to execute directives, and those directives will not be ambiguous.

[Advances of Molecular Diagnostic Techniques Application in Clinical Diagnosis.

PubMed

Ying, Bin-Wu

2016-11-01

Over the past 20 years,clinical molecular diagnostic technology has made rapid development,and became the most promising field in clinical laboratory medicine.In particular,with the development of genomics,clinical molecular diagnostic methods will reveal the nature of clinical diseases in a deeper level,thus guiding the clinical diagnosis and treatments.Many molecular diagnostic projects have been routinely applied in clinical works.This paper reviews the advances on application of clinical diagnostic techniques in infectious disease,tumor and genetic disorders,including nucleic acid amplification,biochip,next-generation sequencing,and automation molecular system,and so on.

Vision 20/20: Automation and advanced computing in clinical radiation oncology

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

Moore, Kevin L., E-mail: kevinmoore@ucsd.edu; Moiseenko, Vitali; Kagadis, George C.

This Vision 20/20 paper considers what computational advances are likely to be implemented in clinical radiation oncology in the coming years and how the adoption of these changes might alter the practice of radiotherapy. Four main areas of likely advancement are explored: cloud computing, aggregate data analyses, parallel computation, and automation. As these developments promise both new opportunities and new risks to clinicians and patients alike, the potential benefits are weighed against the hazards associated with each advance, with special considerations regarding patient safety under new computational platforms and methodologies. While the concerns of patient safety are legitimate, the authorsmore » contend that progress toward next-generation clinical informatics systems will bring about extremely valuable developments in quality improvement initiatives, clinical efficiency, outcomes analyses, data sharing, and adaptive radiotherapy.« less

Vision 20/20: Automation and advanced computing in clinical radiation oncology

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

Moore, Kevin L., E-mail: kevinmoore@ucsd.edu; Moiseenko, Vitali; Kagadis, George C.

2014-01-15

This Vision 20/20 paper considers what computational advances are likely to be implemented in clinical radiation oncology in the coming years and how the adoption of these changes might alter the practice of radiotherapy. Four main areas of likely advancement are explored: cloud computing, aggregate data analyses, parallel computation, and automation. As these developments promise both new opportunities and new risks to clinicians and patients alike, the potential benefits are weighed against the hazards associated with each advance, with special considerations regarding patient safety under new computational platforms and methodologies. While the concerns of patient safety are legitimate, the authorsmore » contend that progress toward next-generation clinical informatics systems will bring about extremely valuable developments in quality improvement initiatives, clinical efficiency, outcomes analyses, data sharing, and adaptive radiotherapy.« less

Vision 20/20: Automation and advanced computing in clinical radiation oncology.

PubMed

Moore, Kevin L; Kagadis, George C; McNutt, Todd R; Moiseenko, Vitali; Mutic, Sasa

2014-01-01

This Vision 20/20 paper considers what computational advances are likely to be implemented in clinical radiation oncology in the coming years and how the adoption of these changes might alter the practice of radiotherapy. Four main areas of likely advancement are explored: cloud computing, aggregate data analyses, parallel computation, and automation. As these developments promise both new opportunities and new risks to clinicians and patients alike, the potential benefits are weighed against the hazards associated with each advance, with special considerations regarding patient safety under new computational platforms and methodologies. While the concerns of patient safety are legitimate, the authors contend that progress toward next-generation clinical informatics systems will bring about extremely valuable developments in quality improvement initiatives, clinical efficiency, outcomes analyses, data sharing, and adaptive radiotherapy.

Clinical cancer advances 2007: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

PubMed

Gralow, Julie; Ozols, Robert F; Bajorin, Dean F; Cheson, Bruce D; Sandler, Howard M; Winer, Eric P; Bonner, James; Demetri, George D; Curran, Walter; Ganz, Patricia A; Kramer, Barnett S; Kris, Mark G; Markman, Maurie; Mayer, Robert J; Raghavan, Derek; Ramsey, Scott; Reaman, Gregory H; Sawaya, Raymond; Schuchter, Lynn M; Sweetenham, John W; Vahdat, Linda T; Davidson, Nancy E; Schilsky, Richard L; Lichter, Allen S

2008-01-10

A MESSAGE FROM ASCO'S PRESIDENT: For the third year, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant cancer research presented or published over the past year. ASCO publishes this report to demonstrate the important progress being made on the front lines of clinical cancer research today. The report is intended to give all those with an interest in cancer care-the general public, cancer patients and organizations, policymakers, oncologists, and other medical professionals-an accessible summary of the year's most important cancer research advances. These pages report on the use of magnetic resonance imaging for breast cancer screening, the association between hormone replacement therapy and breast cancer incidence, the link between human papillomavirus and head and neck cancers, and the use of radiation therapy to prevent lung cancer from spreading. They also report on effective new targeted therapies for cancers that have been historically difficult to treat, such as liver cancer and kidney cancer, among many others. A total of 24 advances are featured in this year's report. These advances and many more over the past several years show that the nation's long-term investment in cancer research is paying off. But there are disturbing signs that progress could slow. We are now in the midst of the longest sustained period of flat government funding for cancer research in history. The budgets for the National Institutes of Health and the National Cancer Institute (NCI) have been unchanged for four years. When adjusted for inflation, cancer research funding has actually declined 12% since 2004. These budget constraints limit the NCI's ability to fund promising cancer research. In the past several years the number of grants that the NCI has been able to fund has significantly decreased; this year, in response to just the

Clinical cancer advances 2006: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

PubMed

Ozols, Robert F; Herbst, Roy S; Colson, Yolonda L; Gralow, Julie; Bonner, James; Curran, Walter J; Eisenberg, Burton L; Ganz, Patricia A; Kramer, Barnett S; Kris, Mark G; Markman, Maurie; Mayer, Robert J; Raghavan, Derek; Reaman, Gregory H; Sawaya, Raymond; Schilsky, Richard L; Schuchter, Lynn M; Sweetenham, John W; Vahdat, Linda T; Winn, Rodger J

2007-01-01

A MESSAGE FROM ASCO's PRESIDENT For the second consecutive year, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant cancer research presented or published over the past year. ASCO developed this report to demonstrate the enormous progress being made on the front lines of cancer research today. The report is intended to give all those with an interest in cancer care-the general public, cancer patients and physicians, policymakers, oncologists, and other medical professionals-an accessible summary of the year's most important cancer research advances. These pages report on new targeted therapies that are improving survival and response rates in hard-to-treat cancers such as kidney cancer, HER-2-positive breast cancer, head and neck cancer, and chronic myelogenous leukemia; the FDA's approval of the world's first preventive vaccine for human papillomavirus (HPV), which has the potential to dramatically reduce the global burden of cervical cancer; and advances in the fast-growing field of personalized medicine, including a new lung cancer test that could help physicians better target treatments and predict prognosis. These advances are only part of the landscape. Survival rates are on the rise, the number of cancer deaths in the United States began declining for the first time since 1930, and new research is showing that the rates of certain common cancers, such as those of the breast and colon, have stabilized, and may have even begun to decline. However, cancer research still faces a number of major obstacles. At a time of extraordinary scientific potential, declining federal funding of cancer research threatens to stall or even reverse recent progress. Such funding cuts have already led to fewer clinical trials, fewer talented young physicians entering the field, and a growing bottleneck of basic science discoveries

Clinical benefit of antiangiogenic therapy in advanced and metastatic chondrosarcoma.

PubMed

Jones, Robin L; Katz, Daniela; Loggers, Elizabeth T; Davidson, Darin; Rodler, Eve T; Pollack, Seth M

2017-08-29

Chondrosarcoma is the most common bone sarcoma in adults. Conventional chondrosarcoma, the commonest histological subtype, is largely resistant to anthracycline-based chemotherapy. There have been anecdotal reports of durable clinical benefit with antiangiogenic agents in this disease. A retrospective search of patients treated at three sarcoma referral centers was performed to identify patients with advanced chondrosarcoma treated with antiangiogenic agents. The aim of this study was to evaluate the efficacy and safety of antiangiogenic agents in advanced chondrosarcoma. Ten patients were identified; seven with conventional, one each with clear cell, extraskeletal mesenchymal chondrosarcoma and extraskeletal myxoid chondrosarcoma. The median progression-free survival for patients with conventional and clear cell sarcoma was 22.6 months. Median overall survival has not been met. Antiangiogenic therapy was well tolerated in this series of patients. Our retrospective data suggest that antiangiogenic therapy can provide prolonged clinical benefit in advanced chondrosarcoma patients. Further prospective trials are required to precisely define the role of this class of agent in advanced chondrosarcoma.

Solutions to an advanced functional partial differential equation of the pantograph type

PubMed Central

Zaidi, Ali A.; Van Brunt, B.; Wake, G. C.

2015-01-01

A model for cells structured by size undergoing growth and division leads to an initial boundary value problem that involves a first-order linear partial differential equation with a functional term. Here, size can be interpreted as DNA content or mass. It has been observed experimentally and shown analytically that solutions for arbitrary initial cell distributions are asymptotic as time goes to infinity to a certain solution called the steady size distribution. The full solution to the problem for arbitrary initial distributions, however, is elusive owing to the presence of the functional term and the paucity of solution techniques for such problems. In this paper, we derive a solution to the problem for arbitrary initial cell distributions. The method employed exploits the hyperbolic character of the underlying differential operator, and the advanced nature of the functional argument to reduce the problem to a sequence of simple Cauchy problems. The existence of solutions for arbitrary initial distributions is established along with uniqueness. The asymptotic relationship with the steady size distribution is established, and because the solution is known explicitly, higher-order terms in the asymptotics can be readily obtained. PMID:26345391

Solutions to an advanced functional partial differential equation of the pantograph type.

PubMed

Zaidi, Ali A; Van Brunt, B; Wake, G C

2015-07-08

A model for cells structured by size undergoing growth and division leads to an initial boundary value problem that involves a first-order linear partial differential equation with a functional term. Here, size can be interpreted as DNA content or mass. It has been observed experimentally and shown analytically that solutions for arbitrary initial cell distributions are asymptotic as time goes to infinity to a certain solution called the steady size distribution. The full solution to the problem for arbitrary initial distributions, however, is elusive owing to the presence of the functional term and the paucity of solution techniques for such problems. In this paper, we derive a solution to the problem for arbitrary initial cell distributions. The method employed exploits the hyperbolic character of the underlying differential operator, and the advanced nature of the functional argument to reduce the problem to a sequence of simple Cauchy problems. The existence of solutions for arbitrary initial distributions is established along with uniqueness. The asymptotic relationship with the steady size distribution is established, and because the solution is known explicitly, higher-order terms in the asymptotics can be readily obtained.

A Patient Focused Solution for Enrolling Clinical Trials in Rare and Selective Cancer Indications: A Landscape of Haystacks and Needles

PubMed Central

Lynam, Eric B.; Leaw, Jiin; Wiener, Matthew B.

2013-01-01

Participation of adult cancer patients in US based clinical trials has remained near 3% for decades. Traditional research methodology reaches a small fraction of the target population with a fixed number of predetermined sites. Solutions are needed to ethically increase patient participation and accelerate cancer trial completion. We compared enrollment outcomes of traditional and patient focused research methodologies. A patient prioritized method (Just-In-Time, JIT) was implemented in parallel with traditionally managed sites in three cancer trials. JIT research sites were initiated after candidate patients presented, while traditional sites were initiated in advance. JIT sites enrolled with mean rates no less than, and up to 2.75 fold greater than, traditional sites. Mean patients enrolled per site was comparable (JIT-1.82, traditional-1.78). There were fewer non-enrolling JIT sites (2/28, 7%) compared to traditional sites 19/52, 37%). This retrospective analysis supports JIT as a prospective solution to increase cancer clinical trial enrollment and the efficiency of clinical trial administrative activities. PMID:23990689

[Advanced Parkinson's disease: clinical characteristics and treatment (part 1)].

PubMed

Kulisevsky, J; Luquin, M R; Arbelo, J M; Burguera, J A; Carrillo, F; Castro, A; Chacón, J; García-Ruiz, P J; Lezcano, E; Mir, P; Martinez-Castrillo, J C; Martínez-Torres, I; Puente, V; Sesar, A; Valldeoriola-Serra, F; Yañez, R

2013-10-01

A large percentage of patients with Parkinson's disease (PD) develop motor fluctuations, dyskinesias, and severe non-motor symptoms within 3 to 5 years of starting dopaminergic therapy, and these motor complications are refractory to treatment. Several authors refer to this stage of the disease as advanced Parkinson's disease. To define the clinical manifestations of advanced PD and the risk factors for reaching this stage of the disease. This consensus document has been prepared by using an exhaustive literature search and by discussion of the contents by an expert group on movement disorders of the Sociedad Española de Neurología (Spanish Neurology Society), coordinated by two of the authors (JK and MRL). Severe motor fluctuations and dyskinesias, axial motor symptoms resistant to levodopa, and cognitive decline are the main signs in the clinical phenotype of advanced PD. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

The role of the clinical nurse specialist/neonatal nurse practitioner in a breastfeeding clinic: a model of advanced practice.

PubMed

Gibbins, S A; Green, P E; Scott, P A; MacDonell, J W

2000-03-01

A commitment to quality health care requires the development of innovative models of care. An example of such a model is the Clinical Nurse Specialist/Neonatal Nurse Practitioner in the role as consultant to Lactation Consultants in a large breastfeeding clinic. The role of the Clinical Nurse Specialist/Neonatal Nurse Practitioner in this ambulatory setting encompasses all the dimensions of the advanced practice model including research, leadership, education, and clinical practice. The evolution of this model of care is described. A conceptual framework of this advanced practice model is presented, supported by examples of the role in the clinic.

The Effect of Solution Heat Treatment on an Advanced Nickel-Base Disk Alloy

NASA Technical Reports Server (NTRS)

Gayda, J.; Gabb, T. P.; Kantzos, P. T.

2004-01-01

Five heat treat options for an advanced nickel-base disk alloy, LSHR, have been investigated. These included two conventional solution heat treat cycles, subsolvus/oil quench and supersolvus/fan cool, which yield fine grain and coarse grain microstructure disks respectively, as well as three advanced dual microstructure heat treat (DMHT) options. The DMHT options produce disks with a fine grain bore and a coarse grain rim. Based on an overall evaluation of the mechanical property data, it was evident that the three DMHT options achieved a desirable balance of properties in comparison to the conventional solution heat treatments for the LSHR alloy. However, one of the DMHT options, SUB/DMHT, produced the best set of properties, largely based on dwell crack growth data. Further evaluation of the SUB/DMHT option in spin pit experiments on a generic disk shape demonstrated the advantages and reliability of a dual grain structure at the component level.

Advances in clinical immunology in 2015.

PubMed

Chinen, Javier; Notarangelo, Luigi D; Shearer, William T

2016-12-01

Advances in clinical immunology in the past year included the report of practice parameters for the diagnosis and management of primary immunodeficiencies to guide the clinician in the approach to these relatively uncommon disorders. We have learned of new gene defects causing immunodeficiency and of new phenotypes expanding the spectrum of conditions caused by genetic mutations such as a specific regulator of telomere elongation (RTEL1) mutation causing isolated natural killer cell deficiency and mutations in ras-associated RAB (RAB27) resulting in immunodeficiency without albinism. Advances in diagnosis included the increasing use of whole-exome sequencing to identify gene defects and the measurement of serum free light chains to identify secondary hypogammaglobulinemias. For several primary immunodeficiencies, improved outcomes have been reported after definitive therapy with hematopoietic stem cell transplantation and gene therapy. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Construction of databases: advances and significance in clinical research.

PubMed

Long, Erping; Huang, Bingjie; Wang, Liming; Lin, Xiaoyu; Lin, Haotian

2015-12-01

Widely used in clinical research, the database is a new type of data management automation technology and the most efficient tool for data management. In this article, we first explain some basic concepts, such as the definition, classification, and establishment of databases. Afterward, the workflow for establishing databases, inputting data, verifying data, and managing databases is presented. Meanwhile, by discussing the application of databases in clinical research, we illuminate the important role of databases in clinical research practice. Lastly, we introduce the reanalysis of randomized controlled trials (RCTs) and cloud computing techniques, showing the most recent advancements of databases in clinical research.

Advances in Probes and Methods for Clinical EPR Oximetry

PubMed Central

Hou, Huagang; Khan, Nadeem; Jarvis, Lesley A.; Chen, Eunice Y.; Williams, Benjamin B.; Kuppusamy, Periannan

2015-01-01

EPR oximetry, which enables reliable, accurate, and repeated measurements of the partial pressure of oxygen in tissues, provides a unique opportunity to investigate the role of oxygen in the pathogenesis and treatment of several diseases including cancer, stroke, and heart failure. Building on significant advances in the in vivo application of EPR oximetry for small animal models of disease, we are developing suitable probes and instrumentation required for use in human subjects. Our laboratory has established the feasibility of clinical EPR oximetry in cancer patients using India ink, the only material presently approved for clinical use. We now are developing the next generation of probes, which are both superior in terms of oxygen sensitivity and biocompatibility including an excellent safety profile for use in humans. Further advances include the development of implantable oxygen sensors linked to an external coupling loop for measurements of deep-tissue oxygenations at any depth, overcoming the current limitation of 10 mm. This paper presents an overview of recent developments in our ability to make meaningful measurements of oxygen partial pressures in human subjects under clinical settings. PMID:24729217

Developing and validating advanced divertor solutions on DIII-D for next-step fusion devices

NASA Astrophysics Data System (ADS)

Guo, H. Y.; Hill, D. N.; Leonard, A. W.; Allen, S. L.; Stangeby, P. C.; Thomas, D.; Unterberg, E. A.; Abrams, T.; Boedo, J.; Briesemeister, A. R.; Buchenauer, D.; Bykov, I.; Canik, J. M.; Chrobak, C.; Covele, B.; Ding, R.; Doerner, R.; Donovan, D.; Du, H.; Elder, D.; Eldon, D.; Lasa, A.; Groth, M.; Guterl, J.; Jarvinen, A.; Hinson, E.; Kolemen, E.; Lasnier, C. J.; Lore, J.; Makowski, M. A.; McLean, A.; Meyer, B.; Moser, A. L.; Nygren, R.; Owen, L.; Petrie, T. W.; Porter, G. D.; Rognlien, T. D.; Rudakov, D.; Sang, C. F.; Samuell, C.; Si, H.; Schmitz, O.; Sontag, A.; Soukhanovskii, V.; Wampler, W.; Wang, H.; Watkins, J. G.

2016-12-01

A major challenge facing the design and operation of next-step high-power steady-state fusion devices is to develop a viable divertor solution with order-of-magnitude increases in power handling capability relative to present experience, while having acceptable divertor target plate erosion and being compatible with maintaining good core plasma confinement. A new initiative has been launched on DIII-D to develop the scientific basis for design, installation, and operation of an advanced divertor to evaluate boundary plasma solutions applicable to next step fusion experiments beyond ITER. Developing the scientific basis for fusion reactor divertor solutions must necessarily follow three lines of research, which we plan to pursue in DIII-D: (1) Advance scientific understanding and predictive capability through development and comparison between state-of-the art computational models and enhanced measurements using targeted parametric scans; (2) Develop and validate key divertor design concepts and codes through innovative variations in physical structure and magnetic geometry; (3) Assess candidate materials, determining the implications for core plasma operation and control, and develop mitigation techniques for any deleterious effects, incorporating development of plasma-material interaction models. These efforts will lead to design, installation, and evaluation of an advanced divertor for DIII-D to enable highly dissipative divertor operation at core density (n e/n GW), neutral fueling and impurity influx most compatible with high performance plasma scenarios and reactor relevant plasma facing components (PFCs). This paper highlights the current progress and near-term strategies of boundary/PMI research on DIII-D.

Developing and validating advanced divertor solutions on DIII-D for next-step fusion devices

DOE PAGES

Guo, H. Y.; Hill, D. N.; Leonard, A. W.; ...

2016-09-14

A major challenge facing the design and operation of next-step high-power steady-state fusion devices is to develop a viable divertor solution with order-of-magnitude increases in power handling capability relative to present experience, while having acceptable divertor target plate erosion and being compatible with maintaining good core plasma confinement. A new initiative has been launched on DIII-D to develop the scientific basis for design, installation, and operation of an advanced divertor to evaluate boundary plasma solutions applicable to next step fusion experiments beyond ITER. Developing the scientific basis for fusion reactor divertor solutions must necessarily follow three lines of research, whichmore » we plan to pursue in DIII-D: (1) Advance scientific understanding and predictive capability through development and comparison between state-of-the art computational models and enhanced measurements using targeted parametric scans; (2) Develop and validate key divertor design concepts and codes through innovative variations in physical structure and magnetic geometry; (3) Assess candidate materials, determining the implications for core plasma operation and control, and develop mitigation techniques for any deleterious effects, incorporating development of plasma-material interaction models. These efforts will lead to design, installation, and evaluation of an advanced divertor for DIII-D to enable highly dissipative divertor operation at core density (n e/n GW), neutral fueling and impurity influx most compatible with high performance plasma scenarios and reactor relevant plasma facing components (PFCs). In conclusion, this paper highlights the current progress and near-term strategies of boundary/PMI research on DIII-D.« less

Clinical ethics consultation's dilemma, and a solution.

PubMed

Rasmussen, Lisa M

2011-01-01

Clinical ethics consultation is on the horns of a dilemma. One horn skewers the field for its lack of standards, while the other horn skewers it for proposing arbitrary or deeply contested foundations. I articulate the dilemma by discussing several critiques of the field and the challenge of formulating standards and suggest that the solution lies, at least until a robust consensus emerges, with establishing a list of proscriptive standards to guide the field.

Clinical and radiographic evaluation of maxillary central incisors exposure in patients undergoing maxillary advancement

PubMed Central

Trento, Guilherme dos Santos; Bernabé, Felipe Bueno Rosettti; da Costa, Delson João; Rebellato, Nelson Luis Barbosa; Klüppel, Leandro Eduardo; Scariot, Rafaela

2015-01-01

Abstract Introduction: Patients with dentofacial deformities may undergo orthodontic or orthodontic-surgical treatment. Both modalities can affect esthetics. Objective: This study aims to evaluate clinical and radiographic changes in exposure of maxillary central incisors occurring after orthognathic surgery for maxillary advancement. Methods: A total of 17 patients who underwent orthognathic surgery for maxillary advancement between September, 2010 and July, 2011 were selected. Exposure of maxillary central incisors was evaluated clinically and by lateral cephalograms. Measurements were taken one week before and three months after surgery. Data were paired in terms of sex, age, nasolabial angle, height and thickness of the upper lip, the amount of maxillary advancement, clinical exposure and inclination of maxillary central incisor by statistical tests (CI 95%). Results: After maxillary advancement, incisor clinical exposure had increased even with relaxed lips and under forced smile. Moreover, there was a mean increase of 23.33% revealed by lateral cephalograms. There was an inverse correlation between upper lip thickness and incisors postsurgical exposure revealed by radiographic images (p = 0.002). Conclusions: Significant changes in the exposure of maxillary central incisors occur after maxillary advancement, under the influence of some factors, especially lip thickness. PMID:26691970

Exploring the scope of expanding advanced nursing practice in nurse-led clinics: a multiple-case study.

PubMed

Shiu, Ann T Y; Lee, Diana T F; Chau, Janita P C

2012-08-01

This article is a report on a study to explore the development of expanding advanced nursing practice in nurse-led clinics in Hong Kong. Nurse-led clinics serviced by advanced practice nurses, a common international practice, have been adopted in Hong Kong since 1990s. Evaluations consistently show that this practice has good clinical outcomes and contributes to containing healthcare cost. However, similar to the international literature, it remains unclear as to what the elements of good advanced nursing practice are, and which directions Hong Kong should adopt for further development of such practice. A multiple-case study design was adopted with six nurse-led clinics representing three specialties as six case studies, and including two clinics each from continence, diabetes and wound care. Each case had four embedded units of analysis. They included non-participant observation of nursing activities (9 days), nurse interviews (N = 6), doctor interviews (N = 6) and client interviews (N = 12). The data were collected in 2009. Within- and cross-case analyses were conducted. The cross-case analysis demonstrated six elements of good advanced nursing practice in nurse-led clinics, and showed a great potential to expand the practice by reshaping four categories of current boundaries, including community-hospital, wellness-illness, public-private and professional-practice boundaries. From these findings, we suggest a model to advance the scope of advanced nursing practice in nurse-led clinics. The six elements may be applied as audit criteria for evaluation of advanced nursing practice in nurse-led clinics, and the proposed model provides directions for expanding such practice in Hong Kong and beyond. © 2011 Blackwell Publishing Ltd.

A forward-advancing wave expansion method for numerical solution of large-scale sound propagation problems

NASA Astrophysics Data System (ADS)

Rolla, L. Barrera; Rice, H. J.

2006-09-01

In this paper a "forward-advancing" field discretization method suitable for solving the Helmholtz equation in large-scale problems is proposed. The forward wave expansion method (FWEM) is derived from a highly efficient discretization procedure based on interpolation of wave functions known as the wave expansion method (WEM). The FWEM computes the propagated sound field by means of an exclusively forward advancing solution, neglecting the backscattered field. It is thus analogous to methods such as the (one way) parabolic equation method (PEM) (usually discretized using standard finite difference or finite element methods). These techniques do not require the inversion of large system matrices and thus enable the solution of large-scale acoustic problems where backscatter is not of interest. Calculations using FWEM are presented for two propagation problems and comparisons to data computed with analytical and theoretical solutions and show this forward approximation to be highly accurate. Examples of sound propagation over a screen in upwind and downwind refracting atmospheric conditions at low nodal spacings (0.2 per wavelength in the propagation direction) are also included to demonstrate the flexibility and efficiency of the method.

Recent Advances in Clinical Natural Language Processing in Support of Semantic Analysis.

PubMed

Velupillai, S; Mowery, D; South, B R; Kvist, M; Dalianis, H

2015-08-13

We present a review of recent advances in clinical Natural Language Processing (NLP), with a focus on semantic analysis and key subtasks that support such analysis. We conducted a literature review of clinical NLP research from 2008 to 2014, emphasizing recent publications (2012-2014), based on PubMed and ACL proceedings as well as relevant referenced publications from the included papers. Significant articles published within this time-span were included and are discussed from the perspective of semantic analysis. Three key clinical NLP subtasks that enable such analysis were identified: 1) developing more efficient methods for corpus creation (annotation and de-identification), 2) generating building blocks for extracting meaning (morphological, syntactic, and semantic subtasks), and 3) leveraging NLP for clinical utility (NLP applications and infrastructure for clinical use cases). Finally, we provide a reflection upon most recent developments and potential areas of future NLP development and applications. There has been an increase of advances within key NLP subtasks that support semantic analysis. Performance of NLP semantic analysis is, in many cases, close to that of agreement between humans. The creation and release of corpora annotated with complex semantic information models has greatly supported the development of new tools and approaches. Research on non-English languages is continuously growing. NLP methods have sometimes been successfully employed in real-world clinical tasks. However, there is still a gap between the development of advanced resources and their utilization in clinical settings. A plethora of new clinical use cases are emerging due to established health care initiatives and additional patient-generated sources through the extensive use of social media and other devices.

Recent Advances in Clinical Natural Language Processing in Support of Semantic Analysis

PubMed Central

Mowery, D.; South, B. R.; Kvist, M.; Dalianis, H.

2015-01-01

Summary Objectives We present a review of recent advances in clinical Natural Language Processing (NLP), with a focus on semantic analysis and key subtasks that support such analysis. Methods We conducted a literature review of clinical NLP research from 2008 to 2014, emphasizing recent publications (2012-2014), based on PubMed and ACL proceedings as well as relevant referenced publications from the included papers. Results Significant articles published within this time-span were included and are discussed from the perspective of semantic analysis. Three key clinical NLP subtasks that enable such analysis were identified: 1) developing more efficient methods for corpus creation (annotation and de-identification), 2) generating building blocks for extracting meaning (morphological, syntactic, and semantic subtasks), and 3) leveraging NLP for clinical utility (NLP applications and infrastructure for clinical use cases). Finally, we provide a reflection upon most recent developments and potential areas of future NLP development and applications. Conclusions There has been an increase of advances within key NLP subtasks that support semantic analysis. Performance of NLP semantic analysis is, in many cases, close to that of agreement between humans. The creation and release of corpora annotated with complex semantic information models has greatly supported the development of new tools and approaches. Research on non-English languages is continuously growing. NLP methods have sometimes been successfully employed in real-world clinical tasks. However, there is still a gap between the development of advanced resources and their utilization in clinical settings. A plethora of new clinical use cases are emerging due to established health care initiatives and additional patient-generated sources through the extensive use of social media and other devices. PMID:26293867

Lost in Translation: The Unintended Consequences of Advance Directive Law on Clinical Care

PubMed Central

Castillo, Lesley S.; Williams, Brie A.; Hooper, Sarah M.; Sabatino, Charles P.; Weithorn, Lois A.; Sudore, Rebecca L.

2011-01-01

Background Advance directive law may compromise the clinical effectiveness of advance directives. Purpose To identify unintended legal consequences of advance directive law that may prevent patients from communicating end-of-life preferences. Data Sources Advance directive legal statutes for all 50 U.S. states and the District of Columbia and English-language searches of LexisNexis, Westlaw, and MEDLINE from 1966 to August 2010. Study Selection Two independent reviewers selected 51 advance directive statutes and 20 articles. Three independent legal reviewers selected 105 legal proceedings. Data Extraction Two reviewers independently assessed data sources and used critical content analysis to determine legal barriers to the clinical effectiveness of advance directives. Disagreements were resolved by consensus. Data Synthesis Legal and content-related barriers included poor readability (that is, laws in all states were written above a 12th-grade reading level), health care agent or surrogate restrictions (for example, 40 states did not include same-sex or domestic partners as default surrogates), and execution requirements needed to make forms legally valid (for example, 35 states did not allow oral advance directives, and 48 states required witness signatures, a notary public, or both). Vulnerable populations most likely to be affected by these barriers included patients with limited literacy, limited English proficiency, or both who cannot read or execute advance directives; same-sex or domestic partners who may be without legally valid and trusted surrogates; and unbefriended, institutionalized, or homeless patients who may be without witnesses and suitable surrogates. Limitation Only appellate-level legal cases were available, which may have excluded relevant cases. Conclusion Unintended negative consequences of advance directive legal restrictions may prevent all patients, and particularly vulnerable patients, from making and communicating their end

Clinical translation of handheld optical coherence tomography: practical considerations and recent advancements

NASA Astrophysics Data System (ADS)

Monroy, Guillermo L.; Won, Jungeun; Spillman, Darold R.; Dsouza, Roshan; Boppart, Stephen A.

2017-12-01

Since the inception of optical coherence tomography (OCT), advancements in imaging system design and handheld probes have allowed for numerous advancements in disease diagnostics and characterization of the structural and optical properties of tissue. OCT system developers continue to reduce form factor and cost, while improving imaging performance (speed, resolution, etc.) and flexibility for applicability in a broad range of fields, and nearly every clinical specialty. An extensive array of components to construct customized systems has also become available, with a range of commercial entities that produce high-quality products, from single components to full systems, for clinical and research use. Many advancements in the development of these miniaturized and portable systems can be linked back to a specific challenge in academic research, or a clinical need in medicine or surgery. Handheld OCT systems are discussed and explored for various applications. Handheld systems are discussed in terms of their relative level of portability and form factor, with mention of the supporting technologies and surrounding ecosystem that bolstered their development. Additional insight from our efforts to implement systems in several clinical environments is provided. The trend toward well-designed, efficient, and compact handheld systems paves the way for more widespread adoption of OCT into point-of-care or point-of-procedure applications in both clinical and commercial settings.

Advanced clinical insights & practice: ischemic heart disease.

PubMed

Benner, Randall W; Zavarella, Matthew S

2008-03-01

This issue sees the debut of a new series of continuing education articles. The series, Advanced Clinical Insights & Practice, is designed to provide continuing education to an ever-expanding realm of paramedicine that needs more of it: the critical care transport paramedic. Secondly, and equally important, are the benefits that can be reaped by other certification levels reading this feature. For EMT-Basics and Intermediates, it will provide a great enhancement to your core knowledge, although most of the interventions discussed will be beyond your traditional scope. For paramedics, it will augment both your pathophysiological understanding and clinical assessment/management skills of diseases and injuries discussed. Ultimately though, it is hoped that anyone who reads these articles will become a better clinician. The next article will appear in the July issue.

Major clinical research advances in gynecologic cancer in 2013.

PubMed

Suh, Dong Hoon; Kim, Jae-Weon; Kang, Sokbom; Kim, Hak Jae; Lee, Kyung-Hun

2014-07-01

In 2013, 10 topics were selected for major clinical research advances in gynecologic oncology; these included three topics regarding cervical cancer, three regarding ovarian cancer, two regarding endometrial cancer, and one each regarding breast cancer and radiation oncology. For cervical cancer, bevacizumab was first demonstrated to exhibit outstanding clinical efficacy in a recurrent, metastatic setting. Regarding cervical cancer screening, visual inspections with acetic acid in low-resource settings, p16/Ki-67 double staining, and the follow-up results of four randomized controlled trials of human papillomavirus-based screening methods were reviewed. Laparoscopic para-aortic lymphadenectomy before chemoradiation for locally advanced cervical cancer was the final topic for cervical cancer. Regarding front-line ovarian cancer therapies, dose-dense paclitaxel and carboplatin, intraperitoneal chemotherapy, and other targeted agents administered according to combination or maintenance schedules were discussed. Regarding recurrent ovarian cancer treatment, cediranib, olaparib, and farletuzumab were discussed for platinum-sensitive disease. The final overall survival data associated with a combination of bevacizumab and chemotherapy for platinum-resistant disease were briefly summarized. For endometrial cancer, the potential clinical efficacy of metformin, an antidiabetic drug, in obese patients was followed by integrated genomic analyses from the Cancer Genome Atlas Research Network. For breast cancer, three remarkable advances were reviewed: the long-term effects of continued adjuvant tamoxifen for 10 years, the effects of 2-year versus 1-year adjuvant trastuzumab for human epidermal growth factor receptor 2-positive disease, and the approval of pertuzumab in a neoadjuvant setting with a pathologic complete response as the surrogate endpoint. Finally, the recent large studies of intensity-modulated radiotherapy for gynecologic cancer were briefly summarized.

Management of advanced pancreatic cancer in daily clinical practice.

PubMed

Giuliani, Jacopo; Piacentini, Paolo; Bonetti, Andrea

2016-01-01

The aim of this outcome study was to evaluate the management of advanced pancreatic cancer in a real-world clinical practice; few such experiences have been reported in the literature. A retrospective analysis was performed of all consecutive patients with advanced pancreatic ductal adenocarcinoma followed at our medical oncology unit between January 2003 and December 2013. We evaluated 78 patients, mostly with metastatic disease (64.1%). Median follow-up was 10.77 months, by which time 74 patients (94.9%) had died. Median overall survival was 8.29 months. Median age was 67 years. In univariate analysis, pain at onset (p = 0.020), ECOG performance status (p<0.001), stage (p = 0.047), first-line chemotherapy (p<0.001), second-line chemotherapy (p<0.001) and weight loss at diagnosis (p = 0.029) were factors that had an impact on overall survival. In multivariate analysis, the presence of pain at onset (p = 0.043), stage (p = 0.003) and second-line chemotherapy (p = 0.004) were confirmed as independent prognostic factors. Our data, derived from daily clinical practice, confirmed advanced pancreatic cancer as an aggressive malignant disease with a very short expected survival. Second-line treatment seems to provide an advantage in terms of overall survival in patients who showed a partial response as their best response to first-line treatment.

Evidence-based use of electronic clinical tracking systems in advanced practice registered nurse education: an integrative review.

PubMed

Branstetter, M Laurie; Smith, Lynette S; Brooks, Andrea F

2014-07-01

Over the past decade, the federal government has mandated healthcare providers to incorporate electronic health records into practice by 2015. This technological update in healthcare documentation has generated a need for advanced practice RN programs to incorporate information technology into education. The National Organization of Nurse Practitioner Faculties created core competencies to guide program standards for advanced practice RN education. One core competency is Technology and Information Literacy. Educational programs are moving toward the utilization of electronic clinical tracking systems to capture students' clinical encounter data. The purpose of this integrative review was to evaluate current research on advanced practice RN students' documentation of clinical encounters utilizing electronic clinical tracking systems to meet advanced practice RN curriculum outcome goals in information technology as defined by the National Organization of Nurse Practitioner Faculties. The state of the science depicts student' and faculty attitudes, preferences, opinions, and data collections of students' clinical encounters. Although electronic clinical tracking systems were utilized to track students' clinical encounters, these systems have not been evaluated for meeting information technology core competency standards. Educational programs are utilizing electronic clinical tracking systems with limited evidence-based literature evaluating the ability of these systems to meet the core competencies in advanced practice RN programs.

CRC Clinical Trials Management System (CTMS): An Integrated Information Management Solution for Collaborative Clinical Research

PubMed Central

Payne, Philip R.O.; Greaves, Andrew W.; Kipps, Thomas J.

2003-01-01

The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) consists of 9 geographically distributed sites conducting a program of research including both basic science and clinical components. To enable the CRC’s clinical research efforts, a system providing for real-time collaboration was required. CTMS provides such functionality, and demonstrates that the use of novel data modeling, web-application platforms, and management strategies provides for the deployment of an extensible, cost effective solution in such an environment. PMID:14728471

Recent Advances in Characterization of Lignin Polymer by Solution-State Nuclear Magnetic Resonance (NMR) Methodology

PubMed Central

Wen, Jia-Long; Sun, Shao-Long; Xue, Bai-Liang; Sun, Run-Cang

2013-01-01

The demand for efficient utilization of biomass induces a detailed analysis of the fundamental chemical structures of biomass, especially the complex structures of lignin polymers, which have long been recognized for their negative impact on biorefinery. Traditionally, it has been attempted to reveal the complicated and heterogeneous structure of lignin by a series of chemical analyses, such as thioacidolysis (TA), nitrobenzene oxidation (NBO), and derivatization followed by reductive cleavage (DFRC). Recent advances in nuclear magnetic resonance (NMR) technology undoubtedly have made solution-state NMR become the most widely used technique in structural characterization of lignin due to its versatility in illustrating structural features and structural transformations of lignin polymers. As one of the most promising diagnostic tools, NMR provides unambiguous evidence for specific structures as well as quantitative structural information. The recent advances in two-dimensional solution-state NMR techniques for structural analysis of lignin in isolated and whole cell wall states (in situ), as well as their applications are reviewed. PMID:28809313

Impact of advanced monitoring variables on intraoperative clinical decision-making: an international survey.

PubMed

Joosten, Alexandre; Desebbe, Olivier; Suehiro, Koichi; Essiet, Mfonobong; Alexander, Brenton; Ricks, Cameron; Rinehart, Joseph; Faraoni, David; Cecconi, Maurizio; Van der Linden, Philippe; Cannesson, Maxime

2017-02-01

To assess the relationship between the addition of advanced monitoring variables and changes in clinical decision-making. A 15-questions survey was anonymously emailed to international experts and physician members of five anesthesia societies which focused on assessing treatment decisions of clinicians during three realistic clinical scenarios measured at two distinct time points. The first is when typical case information and basic monitoring (T1) were provided, and then once again after the addition of advanced monitoring variables (T2). We hypothesized that the addition of advanced variables would increase the incidence of an optimal therapeutic decision (a priori defined as the answer with the highest percentage of expert agreement) and decrease the variability among the physician's suggested treatments. The survey was completed by 18 experts and 839 physicians. Overall, adding advanced monitoring did not significantly increase physician response accuracy, with the least substantial changes noted on questions related to volume expansion or vasopressor administration. Moreover, advanced monitoring data did not significantly decrease the high level of initial practice variability in physician suggested treatments (P = 0.13), in contrast to the low variability observed within the expert group (P = 0.039). Additionally, 5-10 years of practice (P < 0.0001) and a cardiovascular subspecialty (P = 0.048) were both physician characteristics associated with a higher rate of optimal therapeutic decisions. The addition of advanced variables was of limited benefit for most physicians, further indicating the need for more in depth education on the clinical value and technical understanding of such variables.

Liquid biopsy and its role in an advanced clinical trial for lung cancer.

PubMed

Johann, Donald J; Steliga, Mathew; Shin, Ik J; Yoon, Donghoon; Arnaoutakis, Konstantinos; Hutchins, Laura; Liu, Meeiyueh; Liem, Jason; Walker, Karl; Pereira, Andy; Yang, Mary; Jeffus, Susanne K; Peterson, Erich; Xu, Joshua

2018-02-01

Liquid biopsy methodologies, for the purpose of plasma genotyping of cell-free DNA (cfDNA) of solid tumors, are a new class of novel molecular assays. Such assays are rapidly entering the clinical sphere of research-based monitoring in translational oncology, especially for thoracic malignancies. Potential applications for these blood-based cfDNA assays include: (i) initial diagnosis, (ii) response to therapy and follow-up, (iii) tumor evolution, and (iv) minimal residual disease evaluation. Precision medicine will benefit from cutting-edge molecular diagnostics, especially regarding treatment decisions in the adjuvant setting, where avoiding over-treatment and unnecessary toxicity are paramount. The use of innovative genetic analysis techniques on individual patient tumor samples is being pursued in several advanced clinical trials. Rather than using a categorical treatment plan, the next critical step of therapeutic decision making is providing the "right" cancer therapy for an individual patient, including correct dose and timeframe based on the molecular analysis of the tumor in question. Per the 21st Century Cures Act, innovative clinical trials are integral for biomarker and drug development. This will include advanced clinical trials utilizing: (i) innovative assays, (ii) molecular profiling with cutting-edge bioinformatics, and (iii) clinically relevant animal or tissue models. In this paper, a mini-review addresses state-of-the-art liquid biopsy approaches. Additionally, an on-going advanced clinical trial for lung cancer with novelty through synergizing liquid biopsies, co-clinical trials, and advanced bioinformatics is also presented. Impact statement Liquid biopsy technology is providing a new source for cancer biomarkers, and adds new dimensions in advanced clinical trials. Utilizing a non-invasive routine blood draw, the liquid biopsy provides abilities to address perplexing issues of tumor tissue heterogeneity by identifying mutations in both primary

Clinical leadership development and education for nurses: prospects and opportunities

PubMed Central

Joseph, M Lindell; Huber, Diane L

2015-01-01

With the implementation of the Affordable Care Act, elevated roles for nurses of care coordinator, clinical nurse leader, and advanced practice registered nurse have come to the forefront. Because change occurs so fast, matching development and education to job requirements is a challenging forecasting endeavor. The purpose of this article is to envision clinical leadership development and education opportunities for three emerging roles. The adoption of a common framework for intentional leadership development is proposed for clinical leadership development across the continuum of care. Solutions of innovation and interdependency are framed as core concepts that serve as an opportunity to better inform clinical leadership development and education. Additionally, strategies are proposed to advance knowledge, skills, and abilities for crucial implementation of improvements and new solutions at the point of care. PMID:29355179

Collaborative communication: learning from advanced clinical practice patient consultations.

PubMed

Barratt, Julian

2018-04-28

Advanced nurse practitioners, and nurses aspiring to this role, are required to understand how to communicate effectively and on a collaborative basis with patients and carers during consultations, with the aim of enhancing patient outcomes such as improved patient satisfaction, ability to self-manage healthcare needs and adherence to care plans. This article explores collaborative communication in consultations and how best to achieve this, using the author's doctoral observational research based on the findings of a mixed methods observational study of communication in advanced clinical practice patient consultations. ©2018 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

Developing an advanced practice nurse-led liver clinic.

PubMed

McAfee, Jean L

2012-01-01

End-stage liver disease (ESLD) is a leading cause of digestive disease deaths in the United States and continues to increase exponentially every year. Best practice does not currently recognize or utilize a clinic practice model for ESLD management. Advanced practice registered nurses (APRNs) can impact ESLD disease management by implementing an outpatient clinic care model to focus on treatment compliance, patient education, improvement of patient outcomes, and reduction in hospital admission rates for ESLD patients. A review of 15 research articles was completed to determine the impact APRNs can make on chronic care of ESLD patients. Results from the review support APRN analysis, assessment, diagnosis, treatment, intervention, and evaluation of ESLD patients. The literature reviewed also demonstrates that ESLD patients have improved symptom management when maintained in an outpatient setting, allowing for decreased hospital and insurance expenditures. Following evaluation of the evidence, it was concluded that an APRN-led ESLD clinic merits further study.

Mobility disorders and pain, interrelations that need new research concepts and advanced clinical commitments

PubMed Central

Sajer, Sascha

2017-01-01

This Perspective will discuss topics recently suggested by Prof. Helmut Kern, Vienna, Austria, to advance the research activities of his team, that is: Topic A, 10 years post RISE; Topic B, New research for new solutions on old research questions; Topic C, Working groups on nerve regeneration, training-parameters of seniors in different ages, muscle adaptation; and studies of connective tissue and cartilage. This Perspective summarizes some of the basic concepts and of the evidence-based tools for developing further translational research activities. Clinically relevant results will ask for continuous interests of Basic and Applied Myologists and for the support during the next five to ten years of public and private granting agencies. All together, they will end in protocols, devices and multidisciplinary managements for persons suffering with muscle denervation, neuromuscular-related or non-related pain and for the increasing population of old, older and oldest senior citizens in Europe and beyond. PMID:29299226

Student and Preceptor Advancement in a Dedicated Education Site: Innovation in Clinical Education for Advanced Practice Nurses.

PubMed

Hall, Katherine C; Diffenderfer, Sandy K; Stidham, April; Mullins, Christine M

2018-04-19

In the 1990s, dedicated education units transformed undergraduate preceptorships, but graduate preceptorships remain static. The dyadic nurse practitioner preceptorship model supports an environment where faculty, students, and preceptors may overlook nuances that affect the teaching-learning process. This article describes an innovative clinical education model, Student and Preceptor Advancement in a Dedicated Education Site, designed to improve preceptorships for advanced practice nurses. The focus is on adaptations made to facilitate use in advanced practice nursing programs.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Advancing the educational and career pathway for clinical trials nurses.

PubMed

Scott, Kathleen; White, Kathryn; Roydhouse, Jessica K

2013-04-01

Clinical trials nurses play a pivotal role in the conduct of clinical research, but the educational and career pathway for these nurses remains unclear. This article reports findings from a survey of nurses working in cancer clinical trials research in Australia. Most participants held postgraduate qualifications (42 of 61); however, clinical trials education was primarily attained through short professional development courses. Interest in pursuing trial-specific postgraduate education was high, but barriers were identified, including cost, time, and unclear benefit for career advancement. Job titles varied substantially, which is indicative of an unclear employment pathway. These findings suggest that initiatives to improve the educational and career pathway for clinical trials nurses are needed and should include the following: formal educational preparation, greater consistency in employment status, and clearer career progression. These strategies should be underpinned by broad professional recognition of the clinical trials nurse as a specialized nursing role. Copyright 2013, SLACK Incorporated.

Clinically advancing and promising polymer-based therapeutics.

PubMed

Souery, Whitney N; Bishop, Corey J

2018-02-01

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

Clinical Trial Results Vary Widely, But Always Advance Research | NIH MedlinePlus the Magazine

MedlinePlus

... turn Javascript on. Feature: Clinical Trials Clinical Trial Results Vary Widely, But Always Advance Research Past Issues / ... members met with his surgeon to learn the results: 'When we first met, I told you it ...

Introducing Advanced Clinical Reasoning to an Adult Learning Disability Service

ERIC Educational Resources Information Center

Stansfield, Jois; Matthews, Alison

2014-01-01

The advanced clinical reasoning approach is widely adopted in speech and language therapy practice. This article reports on the introduction of the approach across a multidisciplinary adult learning disability service and staff reports on the impact of this initiative. Staff and team managers reported that the training had a positive impact on…

mHealth Clinic Appointment PC Tablet: Implementation, Challenges and Solutions

PubMed Central

Smith, Carol E.; Spaulding, Ryan; Piamjariyakul, Ubolrat; Werkowitch, Marilyn; Yadrich, Donna Macan; Hooper, Dedrick; Moore, Tyson; Gilroy, Richard

2015-01-01

Background Patients requiring daily intravenous (IV) home parenteral nutrition (HPN) would benefit from in-home professional observation to improve self-care, to assess, detect and prevent serious complications. Aims The study aims are to assess the viability and utility of conducting mobile healthcare (mHealth) videoconference assessments with patients managing lifelong daily 12-hour IV nutrition infusions in their homes. The challenges and solutions to implementing mobile personal computer (PC) tablet based clinic appointments are described. Methods A wireless Apple iPad Mini™ mobile touch-screen tablet computer with 5 mega-pixel camera was loaned to patients. Each tablet had Polycom RealPresence software and a fourth generation (4G) mobile telecommunications data plan. These supported audio-visual mobile videoconferencing encrypted connections between health professionals in their offices and HPN patients and their family members in their homes. Patients’ and professionals’ evaluations of their mHealth clinic experiences are collected. Results Patients (mean age = 41.9, SD = 2.8 years) had been prescribed 12-hour home parenteral nutrition (HPN) infusions daily due short bowel disorders. Patients had been on HPN from 1 to 10 years (M=4, SD=3.6). Evaluation of clinic appointments revealed that 100% of the patients (n=45) and the professionals (n=6) indicated that they can clearly hear and easily see one another. The mHealth audio-visual interactions were highly rated by patients and family members. Professionals highly rated their ability to obtain a medical history and visual inspection of patients. Several challenges were identified and recommendations for resolutions are described. Discussion All patients and professionals highly rated the iPad mHealth clinic appointments for convenience and ease of communicating between homes and offices. An important challenge for all mHealth visits is the clinical professional’s ability to make clinically accurate

Technological advances in perioperative monitoring: Current concepts and clinical perspectives

PubMed Central

Chilkoti, Geetanjali; Wadhwa, Rachna; Saxena, Ashok Kumar

2015-01-01

Minimal mandatory monitoring in the perioperative period recommended by Association of Anesthetists of Great Britain and Ireland and American Society of Anesthesiologists are universally acknowledged and has become an integral part of the anesthesia practice. The technologies in perioperative monitoring have advanced, and the availability and clinical applications have multiplied exponentially. Newer monitoring techniques include depth of anesthesia monitoring, goal-directed fluid therapy, transesophageal echocardiography, advanced neurological monitoring, improved alarm system and technological advancement in objective pain assessment. Various factors that need to be considered with the use of improved monitoring techniques are their validation data, patient outcome, safety profile, cost-effectiveness, awareness of the possible adverse events, knowledge of technical principle and ability of the convenient routine handling. In this review, we will discuss the new monitoring techniques in anesthesia, their advantages, deficiencies, limitations, their comparison to the conventional methods and their effect on patient outcome, if any. PMID:25788767

Technological advances in perioperative monitoring: Current concepts and clinical perspectives.

PubMed

Chilkoti, Geetanjali; Wadhwa, Rachna; Saxena, Ashok Kumar

2015-01-01

Minimal mandatory monitoring in the perioperative period recommended by Association of Anesthetists of Great Britain and Ireland and American Society of Anesthesiologists are universally acknowledged and has become an integral part of the anesthesia practice. The technologies in perioperative monitoring have advanced, and the availability and clinical applications have multiplied exponentially. Newer monitoring techniques include depth of anesthesia monitoring, goal-directed fluid therapy, transesophageal echocardiography, advanced neurological monitoring, improved alarm system and technological advancement in objective pain assessment. Various factors that need to be considered with the use of improved monitoring techniques are their validation data, patient outcome, safety profile, cost-effectiveness, awareness of the possible adverse events, knowledge of technical principle and ability of the convenient routine handling. In this review, we will discuss the new monitoring techniques in anesthesia, their advantages, deficiencies, limitations, their comparison to the conventional methods and their effect on patient outcome, if any.

Clinical Cancer Advances 2013: Annual Report on Progress Against Cancer from the American Society of Clinical Oncology.

PubMed

Patel, Jyoti D; Krilov, Lada; Adams, Sylvia; Aghajanian, Carol; Basch, Ethan; Brose, Marcia S; Carroll, William L; de Lima, Marcos; Gilbert, Mark R; Kris, Mark G; Marshall, John L; Masters, Gregory A; O'Day, Steven J; Polite, Blasé; Schwartz, Gary K; Sharma, Sunil; Thompson, Ian; Vogelzang, Nicholas J; Roth, Bruce J

2014-01-10

Since its founding in 1964, the American Society of Clinical Oncology (ASCO) has been committed to improving cancer outcomes through research and the delivery of quality care. Research is the bedrock of discovering better treatments--providing hope to the millions of individuals who face a cancer diagnosis each year. The studies featured in "Clinical Cancer Advances 2013: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology" represent the invaluable contributions of thousands of patients who participate in clinical trials and the scientists who conduct basic and clinical research. The insights described in this report, such as how cancers hide from the immune system and why cancers may become resistant to targeted drugs, enable us to envision a future in which cancer will be even more controllable and preventable. The scientific process is thoughtful, deliberate, and sometimes slow, but each advance, while helping patients, now also points toward new research questions and unexplored opportunities. Both dramatic and subtle breakthroughs occur so that progress against cancer typically builds over many years. Success requires vision, persistence, and a long-term commitment to supporting cancer research and training. Our nation's longstanding investment in federally funded cancer research has contributed significantly to a growing array of effective new treatments and a much deeper understanding of the drivers of cancer. But despite this progress, our position as a world leader in advancing medical knowledge and our ability to attract the most promising and talented investigators are now threatened by an acute problem: Federal funding for cancer research has steadily eroded over the past decade, and only 15% of the ever-shrinking budget is actually spent on clinical trials. This dismal reality threatens the pace of progress against cancer and undermines our ability to address the continuing needs of our patients. Despite this

Systematic genomic identification of colorectal cancer genes delineating advanced from early clinical stage and metastasis

PubMed Central

2013-01-01

Background Colorectal cancer is the third leading cause of cancer deaths in the United States. The initial assessment of colorectal cancer involves clinical staging that takes into account the extent of primary tumor invasion, determining the number of lymph nodes with metastatic cancer and the identification of metastatic sites in other organs. Advanced clinical stage indicates metastatic cancer, either in regional lymph nodes or in distant organs. While the genomic and genetic basis of colorectal cancer has been elucidated to some degree, less is known about the identity of specific cancer genes that are associated with advanced clinical stage and metastasis. Methods We compiled multiple genomic data types (mutations, copy number alterations, gene expression and methylation status) as well as clinical meta-data from The Cancer Genome Atlas (TCGA). We used an elastic-net regularized regression method on the combined genomic data to identify genetic aberrations and their associated cancer genes that are indicators of clinical stage. We ranked candidate genes by their regression coefficient and level of support from multiple assay modalities. Results A fit of the elastic-net regularized regression to 197 samples and integrated analysis of four genomic platforms identified the set of top gene predictors of advanced clinical stage, including: WRN, SYK, DDX5 and ADRA2C. These genetic features were identified robustly in bootstrap resampling analysis. Conclusions We conducted an analysis integrating multiple genomic features including mutations, copy number alterations, gene expression and methylation. This integrated approach in which one considers all of these genomic features performs better than any individual genomic assay. We identified multiple genes that robustly delineate advanced clinical stage, suggesting their possible role in colorectal cancer metastatic progression. PMID:24308539

Advance directives: the clinical nurse specialist as a change agent.

PubMed

Meehan, Karen Anne

2009-01-01

The purpose of this article is to describe the impact the clinical nurse specialist (CNS) has on the advance directive process within the cardiac surgery patient population. As a change agent, the CNS needs to be able to increase the number of advance directives obtained and increase the provision of dignified, self-directed, quality patient care. With requirements from The Joint Commission and the Patient Self-determination Act, the change in process must take place to ensure that healthcare professionals are doing all they can do to carry out a patient's wishes. The 6-Source Influencer Model is applied to a case study to illustrate the role of the CNS as a change agent. Following this model, the CNS can facilitate lasting institutional change in the advance directive process. Based on the example, it is possible that a CNS can act as a change agent for other patient populations within the healthcare setting.

FOCIS goes south: advances in translational and clinical immunology.

PubMed

Kalergis, Alexis M; Anegon, Ignacio; González, Pablo A

2017-09-01

FOCIS goes South: Advances in Translational and Clinical Immunology was the first Federation of Clinical Immunology Societies (FOCIS) ( www.focisnet.org ) meeting held in Latin America (May 15-17, 2017, Santiago de Chile, Chile). The meeting was organized as a 3-day workshop and was fostered by the Millennium Institute on Immunology and Immunotherapy, a recently nominated FOCIS Center of Excellence. The workshop brought together FOCIS associates, such as members of the FOCIS Board of Directors, Directors of different Centers of Excellence, regional speakers and 350 attendees. The Meeting covered aspects of immune regulation and modulation, as well as immunotherapy in areas of autoimmunity, transplantation, cancer and infectious diseases, among others. The activity also had a full-day immunology course and a day-long flow cytometry course.

Legal Briefing: Medicare Coverage of Advance Care Planning.

PubMed

Pope, Thaddeus Mason

2015-01-01

This issue's "Legal Briefing" column covers the recent decision by the Centers for Medicare and Medicaid Services (CMS) to expand Medicare coverage of advance care planning, beginning 1 January 2016. Since 2009, most "Legal Briefings" in this journal have covered a wide gamut of judicial, legislative, and regulatory developments concerning a particular topic in clinical ethics. In contrast, this "Legal Briefing" is more narrowly focused on one single legal development. This concentration on Medicare coverage of advance care planning seems warranted. Advance care planning is a frequent subject of articles in JCE. After all, it has long been seen as an important, albeit only partial, solution to a significant range of big problems in clinical ethics. These problems range from medical futility disputes to decision making for incapacitated patients who have no available legally authorized surrogate. Consequently, expanded Medicare coverage of advance care planning is a potentially seismic development. It may materially reduce both the frequency and severity of key problems in clinical ethics. Since the sociological, medical, and ethical literature on advance care planning is voluminous, I will not even summarize it here. Instead, I focus on Medicare coverage. I proceed, chronologically, in six stages: 1. Prior Medicare Coverage of Advance Care Planning 2. Proposed Expanded Medicare Coverage in 2015 3. Proposed Expanded Medicare Coverage in 2016 4. The Final Rule Expanding Medicare Coverage in 2016 5. Remaining Issues for CMS to Address in 2017 6. Pending Federal Legislation. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

Implications of utility and deontology for the clinical nurse specialist.

PubMed

Ayres, L

1989-01-01

Faced with prospective payment plans and personnel shortages nurses in advanced clinical practice are under pressure to find practical solutions. These solutions may reflect the institutional philosophy of utility rather than the traditional nursing ethic of deontology, illustrating the need to examine the differences between utilitarian and deontological principles as they affect nursing practice. This paper discusses deontology and utility as they apply to nursing practice, considers how these different philosophical positions may affect advanced practitioners, and describes the current status of ethics in nursing.

Advances in the delivery of RNA therapeutics: from concept to clinical reality.

PubMed

Kaczmarek, James C; Kowalski, Piotr S; Anderson, Daniel G

2017-06-27

The rapid expansion of the available genomic data continues to greatly impact biomedical science and medicine. Fulfilling the clinical potential of genetic discoveries requires the development of therapeutics that can specifically modulate the expression of disease-relevant genes. RNA-based drugs, including short interfering RNAs and antisense oligonucleotides, are particularly promising examples of this newer class of biologics. For over two decades, researchers have been trying to overcome major challenges for utilizing such RNAs in a therapeutic context, including intracellular delivery, stability, and immune response activation. This research is finally beginning to bear fruit as the first RNA drugs gain FDA approval and more advance to the final phases of clinical trials. Furthermore, the recent advent of CRISPR, an RNA-guided gene-editing technology, as well as new strides in the delivery of messenger RNA transcribed in vitro, have triggered a major expansion of the RNA-therapeutics field. In this review, we discuss the challenges for clinical translation of RNA-based therapeutics, with an emphasis on recent advances in delivery technologies, and present an overview of the applications of RNA-based drugs for modulation of gene/protein expression and genome editing that are currently being investigated both in the laboratory as well as in the clinic.

Nanotechnology Strategies To Advance Outcomes in Clinical Cancer Care.

PubMed

Hartshorn, Christopher M; Bradbury, Michelle S; Lanza, Gregory M; Nel, Andre E; Rao, Jianghong; Wang, Andrew Z; Wiesner, Ulrich B; Yang, Lily; Grodzinski, Piotr

2018-01-23

Ongoing research into the application of nanotechnology for cancer treatment and diagnosis has demonstrated its advantages within contemporary oncology as well as its intrinsic limitations. The National Cancer Institute publishes the Cancer Nanotechnology Plan every 5 years since 2005. The most recent iteration helped codify the ongoing basic and translational efforts of the field and displayed its breadth with several evolving areas. From merely a technological perspective, this field has seen tremendous growth and success. However, an incomplete understanding of human cancer biology persists relative to the application of nanoscale materials within contemporary oncology. As such, this review presents several evolving areas in cancer nanotechnology in order to identify key clinical and biological challenges that need to be addressed to improve patient outcomes. From this clinical perspective, a sampling of the nano-enabled solutions attempting to overcome barriers faced by traditional therapeutics and diagnostics in the clinical setting are discussed. Finally, a strategic outlook of the future is discussed to highlight the need for next-generation cancer nanotechnology tools designed to address critical gaps in clinical cancer care.

Handwashing with soap or alcoholic solutions? A randomized clinical trial of its effectiveness.

PubMed

Zaragoza, M; Sallés, M; Gomez, J; Bayas, J M; Trilla, A

1999-06-01

The effectiveness of an alcoholic solution compared with the standard hygienic handwashing procedure during regular work in clinical wards and intensive care units of a large public university hospital in Barcelona was assessed. A prospective, randomized clinical trial with crossover design, paired data, and blind evaluation was done. Eligible health care workers (HCWs) included permanent and temporary HCWs of wards and intensive care units. From each category, a random sample of persons was selected. HCWs were randomly assigned to regular handwashing (liquid soap and water) or handwashing with the alcoholic solution by using a crossover design. The number of colony-forming units on agar plates from hands printing in 3 different samples was counted. A total of 47 HCWs were included. The average reduction in the number of colony-forming units from samples before handwashing to samples after handwashing was 49.6% for soap and water and 88.2% for the alcoholic solution. When both methods were compared, the average number of colony-forming units recovered after the procedure showed a statistically significant difference in favor of the alcoholic solution (P <.001). The alcoholic solution was well tolerated by HCWs. Overall acceptance rate was classified as "good" by 72% of HCWs after 2 weeks use. Of all HCWs included, 9.3% stated that the use of the alcoholic solution worsened minor pre-existing skin conditions. Although the regular use of hygienic soap and water handwashing procedures is the gold standard, the use of alcoholic solutions is effective and safe and deserves more attention, especially in situations in which the handwashing compliance rate is hampered by architectural problems (lack of sinks) or nursing work overload.

Clinical Cancer Advances 2018: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.

PubMed

Heymach, John; Krilov, Lada; Alberg, Anthony; Baxter, Nancy; Chang, Susan Marina; Corcoran, Ryan; Dale, William; DeMichele, Angela; Magid Diefenbach, Catherine S; Dreicer, Robert; Epstein, Andrew S; Gillison, Maura L; Graham, David L; Jones, Joshua; Ko, Andrew H; Lopez, Ana Maria; Maki, Robert G; Rodriguez-Galindo, Carlos; Schilsky, Richard L; Sznol, Mario; Westin, Shannon Neville; Burstein, Harold

2018-04-01

A MESSAGE FROM ASCO'S PRESIDENT I remember when ASCO first conceived of publishing an annual report on the most transformative research occurring in cancer care. Thirteen reports later, the progress we have chronicled is remarkable, and this year is no different. The research featured in ASCO's Clinical Cancer Advances 2018 report underscores the impressive gains in our understanding of cancer and in our ability to tailor treatments to tumors' genetic makeup. The ASCO 2018 Advance of the Year, adoptive cell immunotherapy, allows clinicians to genetically reprogram patients' own immune cells to find and attack cancer cells throughout the body. Chimeric antigen receptor (CAR) T-cell therapy-a type of adoptive cell immunotherapy-has led to remarkable results in young patients with acute lymphoblastic leukemia (ALL) and in adults with lymphoma and multiple myeloma. Researchers are also exploring this approach in other types of cancer. This advance would not be possible without robust federal investment in cancer research. The first clinical trial of CAR T-cell therapy in children with ALL was funded, in part, by grants from the National Cancer Institute (NCI), and researchers at the NCI Center for Cancer Research were the first to report on possible CAR T-cell therapy for multiple myeloma. These discoveries follow decades of prior research on immunology and cancer biology, much of which was supported by federal dollars. In fact, many advances that are highlighted in the 2018 Clinical Cancer Advances report were made possible thanks to our nation's support for biomedical research. Funding from the US National Institutes of Health and the NCI helps researchers pursue critical patient care questions and addresses vital, unmet needs that private industry has little incentive to take on. Federally supported cancer research generates the biomedical innovations that fuel the development and availability of new and improved treatments for patients. We need sustained federal

Barriers and strategies for the clinical translation of advanced orthopaedic tissue engineering protocols.

PubMed

Madry, H; Alini, M; Stoddart, M J; Evans, C; Miclau, T; Steiner, S

2014-05-06

Research in orthopaedic tissue engineering has intensified over the last decade and new protocols continue to emerge. The clinical translation of these new applications, however, remains associated with a number of obstacles. This report highlights the major issues that impede the clinical translation of advanced tissue engineering concepts, discusses strategies to overcome these barriers, and examines the need to increase incentives for translational strategies. The statements are based on presentations and discussions held at the AO Foundation-sponsored symposium "Where Science meets Clinics 2013" held at the Congress Center in Davos, Switzerland, in September, 2013. The event organisers convened a diverse group of over one hundred stakeholders involved in clinical translation of orthopaedic tissue engineering, including scientists, clinicians, healthcare industry professionals and regulatory agency representatives. A major point that emerged from the discussions was that there continues to be a critical need for early trans-disciplinary communication and collaboration in the development and execution of research approaches. Equally importantly was the need to address the shortage of sustained funding programs for multidisciplinary teams conducting translational research. Such detailed discussions between experts contribute towards the development of a roadmap to more successfully advance the clinical translation of novel tissue engineering concepts and ultimately improve patient care in orthopaedic and trauma surgery.

Advances in clinical studies of cardiopulmonary resuscitation

PubMed Central

Chen, Shou-quan

2015-01-01

BACKGROUND: The survival rate of patients after cardiac arrest (CA) remains lower since 2010 International Consensus on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) was published. In clinical trials, the methods and techniques for CPR have been overly described. This article gives an overview of the progress in methods and techniques for CPR in the past years. DATA SOURCES: Original articles about cardiac arrest and CPR from MEDLINE (PubMed) and relevant journals were searched, and most of them were clinical randomized controlled trials (RCTs). RESULTS: Forty-two articles on methods and techniques of CPR were reviewed, including chest compression and conventional CPR, chest compression depth and speed, defibrillation strategies and priority, mechanical and manual chest compression, advanced airway management, impedance threshold device (ITD) and active compression-decompression (ACD) CPR, epinephrine use, and therapeutic hypothermia. The results of studies and related issues described in the international guidelines had been testified. CONCLUSIONS: Although large multicenter studies on CPR are still difficult to carry out, progress has been made in the past 4 years in the methods and techniques of CPR. The results of this review provide evidences for updating the 2015 international guidelines. PMID:26056537

Advanced abdominal pregnancy: an increasingly challenging clinical concern for obstetricians

PubMed Central

Huang, Ke; Song, Lei; Wang, Longxia; Gao, Zhiying; Meng, Yuanguang; Lu, Yanping

2014-01-01

Advanced abdominal pregnancy is rare. The low incidence, high misdiagnosis rate, and lack of specific clinical signs and symptoms explain the fact that there are no standard diagnostic and treatment options available for advanced abdominal pregnancy. We managed a case of abdominal pregnancy in a woman who was pregnant for the first time. This case was further complicated by a concurrent singleton intrauterine pregnancy; the twin pregnancy was not detected until 20 weeks of pregnancy. The case was confirmed at 26 weeks gestational age using MRI to be an abdominal combined with intrauterine pregnancy. The pregnancy was terminated by cesarean section at 33 + 5 weeks gestation. We collected the relevant data of the case while reviewing the advanced abdominal pregnancy-related English literature in the Pubmed, Proquest, and OVID databases. We compared and analyzed the pregnancy history, gestational age when the diagnosis was confirmed, the placental colonization position, the course of treatment and surgical processes, related concurrency rate, post-operative drug treatment programs, and follow-up results with the expectation to provide guidance for other physicians who might encounter similar cases. PMID:25337188

Recent Advances towards the Clinical Application of Stem Cells for Retinal Regeneration

PubMed Central

Becker, Silke; Jayaram, Hari; Limb, G. Astrid

2012-01-01

Retinal degenerative diseases constitute a major cause of irreversible blindness in the world. Stem cell-based therapies offer hope for these patients at risk of or suffering from blindness due to the deterioration of the neural retina. Various sources of stem cells are currently being investigated, ranging from human embryonic stem cells to adult-derived induced pluripotent stem cells as well as human Müller stem cells, with the first clinical trials to investigate the safety and tolerability of human embryonic stem cell-derived retinal pigment epithelium cells having recently commenced. This review aims to summarize the latest advances in the development of stem cell strategies for the replacement of retinal neurons and their supportive cells, the retinal pigment epithelium (RPE) affected by retinal degenerative conditions. Particular emphasis will be given to the advances in stem cell transplantation and the challenges associated with their translation into clinical practice. PMID:24710533

First Brazilian Consensus of Advanced Prostate Cancer: Recommendations for Clinical Practice.

PubMed

Sasse, Andre Deeke; Wiermann, Evanius Garcia; Herchenhorn, Daniel; Bastos, Diogo Assed; Schutz, Fabio A; Maluf, Fernando Cotait; Coura, George; Morbeck, Igor Alexandre Protzner; Cerci, Juliano J; Smaletz, Oren; Lima, Volney Soares; Adamy, Ari; Campos, Franz Santos de; Carvalhal, Gustavo Franco; Cezar, Leandro Casemiro; Dall'Oglio, Marcos Francisco; Sadi, Marcus Vinicius; Reis, Rodolfo Borges Dos; Nogueira, Lucas

2017-01-01

Prostate cancer still represents a major cause of morbidity, and still about 20% of men with the disease are diagnosed or will progress to the advanced stage without the possibility of curative treatment. Despite the recent advances in scientific and technological knowledge and the availability of new therapies, there is still considerable heterogeneity in the therapeutic approaches for metastatic prostate cancer. This article presents a summary of the I Brazilian Consensus on Advanced Prostate Cancer, conducted by the Brazilian Society of Urology and Brazilian Society of Clinical Oncology. Experts were selected by the medical societies involved. Forty issues regarding controversial issues in advanced disease were previously elaborated. The panel met for consensus, with a threshold established for 2/3 of the participants. The treatment of advanced prostate cancer is complex, due to the existence of a large number of therapies, with different response profiles and toxicities. The panel addressed recommendations on preferred choice of therapies, indicators that would justify their change, and indicated some strategies for better sequencing of treatment in order to maximize the potential for disease control with the available therapeutic arsenal. The lack of consensus on some topics clearly indicates the absence of strong evidence for some decisions. Copyright® by the International Brazilian Journal of Urology.

The clinical impact of recent advances in LC-MS for cancer biomarker discovery and verification

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

Wang, Hui; Shi, Tujin; Qian, Wei-Jun

2015-12-04

Mass spectrometry-based proteomics has become an indispensable tool in biomedical research with broad applications ranging from fundamental biology, systems biology, and biomarker discovery. Recent advances in LC-MS have made it become a major technology in clinical applications, especially in cancer biomarker discovery and verification. To overcome the challenges associated with the analysis of clinical samples, such as extremely wide dynamic range of protein concentrations in biofluids and the need to perform high throughput and accurate quantification, significant efforts have been devoted to improve the overall performance of LC-MS bases clinical proteomics. In this review, we summarize the recent advances inmore » LC-MS in the aspect of cancer biomarker discovery and quantification, and discuss its potentials, limitations, and future perspectives.« less

The clinical impact of recent advances in LC-MS for cancer biomarker discovery and verification.

PubMed

Wang, Hui; Shi, Tujin; Qian, Wei-Jun; Liu, Tao; Kagan, Jacob; Srivastava, Sudhir; Smith, Richard D; Rodland, Karin D; Camp, David G

2016-01-01

Mass spectrometry (MS) -based proteomics has become an indispensable tool with broad applications in systems biology and biomedical research. With recent advances in liquid chromatography (LC) and MS instrumentation, LC-MS is making increasingly significant contributions to clinical applications, especially in the area of cancer biomarker discovery and verification. To overcome challenges associated with analyses of clinical samples (for example, a wide dynamic range of protein concentrations in bodily fluids and the need to perform high throughput and accurate quantification of candidate biomarker proteins), significant efforts have been devoted to improve the overall performance of LC-MS-based clinical proteomics platforms. Reviewed here are the recent advances in LC-MS and its applications in cancer biomarker discovery and quantification, along with the potentials, limitations and future perspectives.

Improving quality and patient satisfaction in a pediatric resident continuity clinic through advanced access scheduling.

PubMed

Tuli, Sanjeev Y; Thompson, Lindsay A; Ryan, Kathleen A; Srinivas, Ganga L; Fillipps, Donald J; Young, Christopher M; Tuli, Sonal S

2010-06-01

To evaluate the impact of advanced access scheduling in a pediatric residency clinic on resident and patient satisfaction, medical education, practice quality, and efficiency. Residents were assigned to either the advanced access template (10 appointments available to patients and 2 physician overbooks) or the prior template (5 available and 8 overbooks). Outcomes included resident and patient satisfaction, appointment availability, and continuity of care and clinic costs. Patient satisfaction improved in 7 areas (P < .001). Residents in either template did not report an impact on medical education experiences. Significant increases were realized with appointment availability and the number of patients seen. Continuity also increased as the overflow/acute visits decreased (P < .001). Overall costs per visit decreased 22%. Because of the significant improvements in access, continuity, and efficiency, all residents were switched to the advanced access template after completion of the study. Improvement in access to the primary physician has a significant impact on patient satisfaction with health care delivery. This model optimizes the limited time that residents have in continuity clinic, and it has implications for health care delivery quality improvement.

Advancing description and explanation in clinical linguistics: a legacy of Martin J. Ball.

PubMed

Damico, Jack S; Damico, Holly L; Nelson, Ryan L

2011-11-01

This article asserts the importance of explication of order and disorder in language as a privileged objective of clinical linguistics and service delivery and reviews the contributions of Martin Ball in advancing this agenda.

Management of advanced pancreatic cancer with gemcitabine plus erlotinib: efficacy and safety results in clinical practice.

PubMed

Diaz Beveridge, Robert; Alcolea, Vicent; Aparicio, Jorge; Segura, Ángel; García, Jose; Corbellas, Miguel; Fonfría, María; Giménez, Alejandra; Montalar, Joaquin

2014-01-10

The combination of gemcitabine and erlotinib is a standard first-line treatment for unresectable, locally advanced or metastatic pancreatic cancer. We reviewed our single centre experience to assess its efficacy and toxicity in clinical practice. Clinical records of patients with unresectable, locally advanced or metastatic pancreatic cancer who were treated with the combination of gemcitabine and erlotinib were reviewed. Univariate survival analysis and multivariate analysis were carried out to indentify independent predictors factors of overall survival. Our series included 55 patients. Overall disease control rate was 47%: 5% of patients presented complete response, 20% partial response and 22% stable disease. Median overall survival was 8.3 months). Cox regression analysis indicated that performance status and locally advanced versus metastatic disease were independent factors of overall survival. Patients who developed acne-like rash toxicity, related to erlotinib administration, presented a higher survival than those patients who did not develop this toxicity. Gemcitabine plus erlotinib doublet is active in our series of patients with advanced pancreatic cancer. This study provides efficacy and safety results similar to those of the pivotal phase III clinical trial that tested the same combination.

Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers.

PubMed

Borad, Mitesh J; Egan, Jan B; Condjella, Rachel M; Liang, Winnie S; Fonseca, Rafael; Ritacca, Nicole R; McCullough, Ann E; Barrett, Michael T; Hunt, Katherine S; Champion, Mia D; Patel, Maitray D; Young, Scott W; Silva, Alvin C; Ho, Thai H; Halfdanarson, Thorvardur R; McWilliams, Robert R; Lazaridis, Konstantinos N; Ramanathan, Ramesh K; Baker, Angela; Aldrich, Jessica; Kurdoglu, Ahmet; Izatt, Tyler; Christoforides, Alexis; Cherni, Irene; Nasser, Sara; Reiman, Rebecca; Cuyugan, Lori; McDonald, Jacquelyn; Adkins, Jonathan; Mastrian, Stephen D; Valdez, Riccardo; Jaroszewski, Dawn E; Von Hoff, Daniel D; Craig, David W; Stewart, A Keith; Carpten, John D; Bryce, Alan H

2016-12-23

DNA focused panel sequencing has been rapidly adopted to assess therapeutic targets in advanced/refractory cancer. Integrated Genomic Profiling (IGP) utilising DNA/RNA with tumour/normal comparisons in a Clinical Laboratory Improvement Amendments (CLIA) compliant setting enables a single assay to provide: therapeutic target prioritisation, novel target discovery/application and comprehensive germline assessment. A prospective study in 35 advanced/refractory cancer patients was conducted using CLIA-compliant IGP. Feasibility was assessed by estimating time to results (TTR), prioritising/assigning putative therapeutic targets, assessing drug access, ascertaining germline alterations, and assessing patient preferences/perspectives on data use/reporting. Therapeutic targets were identified using biointelligence/pathway analyses and interpreted by a Genomic Tumour Board. Seventy-five percent of cases harboured 1-3 therapeutically targetable mutations/case (median 79 mutations of potential functional significance/case). Median time to CLIA-validated results was 116 days with CLIA-validation of targets achieved in 21/22 patients. IGP directed treatment was instituted in 13 patients utilising on/off label FDA approved drugs (n = 9), clinical trials (n = 3) and single patient IND (n = 1). Preliminary clinical efficacy was noted in five patients (two partial response, three stable disease). Although barriers to broader application exist, including the need for wider availability of therapies, IGP in a CLIA-framework is feasible and valuable in selection/prioritisation of anti-cancer therapeutic targets.

Developing clinical leaders: the impact of an action learning mentoring programme for advanced practice nurses.

PubMed

Leggat, Sandra G; Balding, Cathy; Schiftan, Dan

2015-06-01

To determine whether a formal mentoring programme assists nurse practitioner candidates to develop competence in the clinical leadership competencies required in their advanced practice roles. Nurse practitioner candidates are required to show evidence of defined clinical leadership competencies when they apply for endorsement within the Australian health care system. Aiming to assist the candidates with the development or enhancement of these leadership skills, 18 nurse practitioner candidates participated in a mentoring programme that matched them with senior nurse mentors. A pre-postlongitudinal intervention study. Eighteen nurse practitioner candidates and 17 senior nurses participated in a voluntary mentoring programme that incorporated coaching and action learning over 18 months in 2012 and 2013. Participants completed a pen and paper questionnaire to document baseline measures of self-reported leadership practices prior to commencement of the programme and again at the end of the programme. The mentors and the nurse practitioner candidates qualitatively evaluated the programme as successful and quantitative data illustrated significant improvement in self-reported leadership practices among the nurse practitioner candidates. In particular, the nurse practitioner candidates reported greater competence in the transformational aspects of leadership, which is directly related to the nurse practitioner candidate clinical leadership standard. A formal, structured mentoring programme based on principles of action learning was successful in assisting Australian advanced practice nurses enhance their clinical leadership skills in preparation for formal endorsement as a nurse practitioner and for success in their advanced practice role. Mentoring can assist nurses to transition to new roles and develop knowledge and skills in clinical leadership essential for advanced practice roles. Nurse managers should make greater use of mentoring programmes to support nurses in

An American and Dutch partnership for psychiatric mental health advance nursing practice: nurturing a relationship across the ocean.

PubMed

Maas, Lillian; Ezeobele, I Ezebuiro; Tetteroo, Marieke

2012-07-01

The purpose of this article is to discuss the challenges and rewards of developing and nurturing an international clinical psychiatric mental health advanced nursing practice exchange between the Netherlands and the United States. Since 1997, Rotterdam University of Applied Sciences in the Netherlands has been participating in international clinical experiences for their psychiatric mental health (PMH) advanced practice nursing students. The international experience is mandatory prior to graduation and is the first of its kind in Europe to mandate such a unique experience. This study sample included eight Dutch PMH advanced practice nursing students enrolled in a full-time master's in advanced nursing practice program. The descriptive study included reflective reports and one-on-one discussions over a 3-year period. With proper planning, an international nursing experience provides a unique opportunity for nurses to think beyond their own culture and healthcare system. Solving problems together through different perspectives creates opportunities for creative solutions. International partnerships within PMH advanced practice nursing promotes sharing of knowledge and solutions as patients and diseases have no border. © 2011 Wiley Periodicals, Inc.

Coronary Stents: The Impact of Technological Advances on Clinical Outcomes.

PubMed

Mennuni, Marco G; Pagnotta, Paolo A; Stefanini, Giulio G

2016-02-01

Percutaneous coronary interventions (PCI) were proposed in the late 1970s as an alternative to surgical coronary artery bypass grafting for the treatment of coronary artery disease. Important technological progress has been made since. Balloon angioplasty was replaced by bare metal stents, which allowed to permanently scaffold the coronary vessel avoiding acute recoil and abrupt occlusion. Thereafter, the introduction of early generation drug-eluting stents (DES) has significantly improved clinical outcomes, primarily by markedly reducing the risk of restenosis. New generation DES with thinner stent struts, novel durable or biodegradable polymer coatings, and new limus antiproliferative agents, have further improved upon the safety and efficacy profile of early generation DES. The present article aims to review the impact of technological advances on clinical outcomes in the field of PCI with coronary stents, and to provide a brief overview on clinical margins of improvement and unmet needs of available DES.

[Advance directives in clinical practice : Living will, healthcare power of attorney and care directive].

PubMed

Hack, J; Buecking, B; Lopez, C L; Ruchholtz, S; Kühne, C A

2017-06-01

In clinical practice, situations continuously occur in which medical professionals and family members are confronted with decisions on whether to extend or limit treatment for severely ill patients in end of life treatment decisions. In these situations, advance directives are helpful tools in decision making according to the wishes of the patient; however, not every patient has made an advance directive and in our experience medical staff as well as patients are often not familiar with these documents. The purpose of this article is therefore to explain the currently available documents (e.g. living will, healthcare power of attorney and care directive) and the possible (legal) applications and limitations in the routine clinical practice.

[Advance directives in clinical practice : Living will, healthcare power of attorney and care directive].

PubMed

Hack, J; Buecking, B; Lopez, C L; Ruchholtz, S; Kühne, C A

2017-02-01

In clinical practice, situations continuously occur in which medical professionals and family members are confronted with decisions on whether to extend or limit treatment for severely ill patients in end of life treatment decisions. In these situations, advance directives are helpful tools in decision making according to the wishes of the patient; however, not every patient has made an advance directive and in our experience medical staff as well as patients are often not familiar with these documents. The purpose of this article is therefore to explain the currently available documents (e.g. living will, healthcare power of attorney and care directive) and the possible (legal) applications and limitations in the routine clinical practice.

[Advance directives in clinical practice : Living will, healthcare power of attorney and care directive].

PubMed

Hack, J; Buecking, B; Lopez, C L; Ruchholtz, S; Kühne, C A

2017-12-01

In clinical practice, situations continuously occur in which medical professionals and family members are confronted with decisions on whether to extend or limit treatment for severely ill patients in end of life treatment decisions. In these situations, advance directives are helpful tools in decision making according to the wishes of the patient; however, not every patient has made an advance directive and in our experience medical staff as well as patients are often not familiar with these documents. The purpose of this article is therefore to explain the currently available documents (e.g. living will, healthcare power of attorney and care directive) and the possible (legal) applications and limitations in the routine clinical practice.

[Advance directives in clinical practice : Living will, healthcare power of attorney and care directive].

PubMed

Hack, J; Buecking, B; Lopez, C L; Ruchholtz, S; Kühne, C A

2017-04-01

In clinical practice, situations continuously occur in which medical professionals and family members are confronted with decisions on whether to extend or limit treatment for severely ill patients in end of life treatment decisions. In these situations, advance directives are helpful tools in decision making according to the wishes of the patient; however, not every patient has made an advance directive and in our experience medical staff as well as patients are often not familiar with these documents. The purpose of this article is therefore to explain the currently available documents (e.g. living will, healthcare power of attorney and care directive) and the possible (legal) applications and limitations in the routine clinical practice.

Clinical Research Environment in India: Challenges and Proposed Solutions

PubMed Central

Burt, Tal; Sharma, Pooja; Dhillon, Savita; Manchanda, Mukul; Mittal, Sanjay; Trehan, Naresh

2015-01-01

India has compelling need and keen aspirations for indigenous clinical research. Notwithstanding this need and previously reported growth the expected expansion of Indian clinical research has not materialized. We reviewed the scientific literature, lay press reports, and ClinicalTrials.gov data for information and commentary on projections, progress, and impediments associated with clinical trials in India. We also propose targeted solutions to identified challenges. The Indian clinical trial sector grew by (+) 20.3% CAGR (compound annual growth rate) between 2005 and 2010 and contracted by (-) 14.6% CAGR between 2010 and 2013. Phase-1 trials grew by (+) 43.5% CAGR from 2005–2013, phase-2 trials grew by (+) 19.8% CAGR from 2005–2009 and contracted by (-) 12.6% CAGR from 2009–2013, and phase-3 trials grew by (+) 13.0% CAGR from 2005–2010 and contracted by (-) 28.8% CAGR from 2010–2013. This was associated with a slowing of the regulatory approval process, increased media coverage and activist engagement, and accelerated development of regulatory guidelines and recuperative initiatives. We propose the following as potential targets for restorative interventions: Regulatory overhaul (leadership and enforcement of regulations, resolution of ambiguity in regulations, staffing, training, guidelines, and ethical principles [e.g., compensation]).Education and training of research professionals, clinicians, and regulators.Public awareness and empowerment. After a peak in 2009-2010, the clinical research sector in India appears to be experiencing a contraction. There are indications of challenges in regulatory enforcement of guidelines; training of clinical research professionals; and awareness, participation, partnership, and the general image amongst the non-professional media and public. Preventative and corrective principles and interventions are outlined with the goal of realizing the clinical research potential in India. PMID:25590017

Exploring the role of advanced nurse practitioners in leadership.

PubMed

Anderson, Claire

2018-05-02

There have been several changes to healthcare services in the UK over recent years, with rising NHS costs and increasing demands on healthcare professionals to deliver high-quality care. Simultaneously, public inquiries have identified suboptimal leadership throughout the NHS, which has been linked to a lack of clear leadership across the healthcare professions. In nursing, the role of the advanced nurse practitioner is regarded as a solution to this leadership challenge. This article examines the background to the development of the advanced nurse practitioner role. It also explores the various factors that may affect nurse leadership and the role of the advanced nurse practitioner, including professional identity, gender, nursing's strategic influence, clinical outcomes, and recruitment and retention. The article concludes that while advanced nurse practitioners can positively influence clinical outcomes and cost efficiency, they must also be adequately prepared to undertake a leadership role. © 2018 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

The integration of traditional and advanced design in the formation of sustainable New Rural Housing solutions.

NASA Astrophysics Data System (ADS)

Khai Tran, Van

2018-04-01

Socio-economic growth in Vietnam greatly depends on the new rural development process in this country; the work is considered a strategic position in national development. Thus, the study of the principles of the architectural design of new rural housing solutions in accordance with the New Rural Environment as required by the Vietnam Ministry of Construction has become urgent. Climate change has become a global concern, so the creation of significant impacts by architectural designs to respond to climate change and make the living environment of rural people better is a major demand. Experience has shown that the dogmatic application of current urban-type housing does not reach the requirements of New Rural Housing. This research intends to show that the solutions of the traditional Vietnamese rural house, which retains the advantages of traditional architecture with excellent characteristics that have been challenged over thousands of years, when combined with advanced design methodologies and technologies, will be the appropriate solution for ‘New Rural Housing’.

Quo vadis radiotherapy? Technological advances and the rising problems in cancer management.

PubMed

Allen, Barry J; Bezak, Eva; Marcu, Loredana G

2013-01-01

Despite the latest technological advances in radiotherapy, cancer control is still challenging for several tumour sites. The survival rates for the most deadly cancers, such as ovarian and pancreatic, have not changed over the last decades. The solution to the problem lies in the change of focus: from local treatment to systemic therapy. The aim of this paper is to present the current status as well as the gaps in radiotherapy and, at the same time, to look into potential solutions to improve cancer control and survival. The currently available advanced radiotherapy treatment techniques have been analysed and their cost-effectiveness discussed. The problem of systemic disease management was specifically targeted. Clinical studies show limited benefit in cancer control from hadron therapy. However, targeted therapies together with molecular imaging could improve treatment outcome for several tumour sites while controlling the systemic disease. The advances in photon therapy continue to be competitive with the much more expensive hadron therapy. To justify the cost effectiveness of proton/heavy ion therapy, there is a need for phase III randomised clinical trials. Furthermore, the success of systemic disease management lies in the fusion between radiation oncology technology and microbiology.

Decolorization and degradation of reactive yellow HF aqueous solutions by electrochemical advanced oxidation processes.

PubMed

Bedolla-Guzman, A; Feria-Reyes, R; Gutierrez-Granados, S; Peralta-Hernández, Juan M

2017-05-01

Textile manufacturing is the one responsible for water bodies' contamination through the discharge of colored wastes. This work presents the study of reactive yellow HF (RYHF) dye degradation under two different electrochemical advanced oxidation processes (EAOP), namely anodic oxidation (AO) and electro-Fenton (EF)/boron-doped diamond (BDD) process. For the AO, 100 and 300 mg/L solutions using Pt and BDD as anodes in a 100 mL stirred tank cell were used, with a supporting electrolyte of 0.05 mol/L of Na 2 SO 4 at pH 3 under 30 and 50 mA/cm 2 current density. The EF/BDD process was carried out in a flow reactor at 4 and 7 L/min to degrade 100, 200, and 300 mg/L RYHF solutions under 50 and 80 mA/cm 2 . UV-Vis determinations were used for decolorization evaluation, while high-performance liquid chromatography (HPLC) method provided information on dye degradation rate.

7th Annual Symposium on Clinical and Pharmaceutical Solutions through Analysis.

PubMed

Zhang, Tianyi Tee; Wang, Li; Weng, Naidong; Dong, Kelly; Valaskovic, Gary; Lee, Mike

2016-10-01

7th Annual Symposium on Clinical & Pharmaceutical Solutions through Analysis, Renaissance Shanghai Pudong Hotel, Shanghai, China, 20-23 April 2016 The 7th Annual Shanghai Symposium on Innovative Approaches to Reduce Attrition and Predict Clinical Outcomes (CPSA Shanghai 2016) was held on 20-23 April 2016 in Renaissance Shanghai Pudong Hotel, Shanghai, China. The meeting was featured with highly interactive events including diversified symposia, round table discussions, workshops, poster sessions and conference awards. There were over 220 participants from more than ten countries, with 61 oral presentations and 29 posters presented. In addition, the meeting included one preconference workshop and three joint sessions held with bioanalytical experts from local communities.

[Application of clinical nursing path in standard management of advanced schistosomiasis patients with splenomegaly].

PubMed

Yang, Liu; Liu, Juan-Juan

2013-04-01

To study the feasibility and effect of clinical nursing path in the standard management of advanced schistosomiasis patients with splenomegaly. A total of 64 advanced schistosomiasis patients with splenomegaly were randomly divided into a routine nursing group (control group) and a clinical nursing pathway group (CNP group), and the postoperative situation, average hospitalization days, cost of hospitalization and the satisfaction of the patients of the 2 groups were compared. The complications, average hospitalization days, costs of hospitalization in the CNP group were significantly decreased compared with those in the control group, and satisfaction rate of the patients in the CNP group increased from 81.25% to 100%. The implementation of CNP effectively reduces the length of hospitalization, costs and complications, and improves the satisfaction of the patients.

Clinical Implementation of Novel Targeted Therapeutics in Advanced Breast Cancer.

PubMed

Chamberlin, Mary D; Bernhardt, Erica B; Miller, Todd W

2016-11-01

The majority of advanced breast cancers have genetic alterations that are potentially targetable with drugs. Through initiatives such as The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), data can be mined to provide context for next-generation sequencing (NGS) results in the landscape of advanced breast cancer. Therapies for targets other than estrogen receptor alpha (ER) and HER2, such as cyclin-dependent kinases CDK4 and CDK6, were recently approved based on efficacy in patient subpopulations, but no predictive biomarkers have been found, leaving clinicians to continue a trial-and-error approach with each patient. Next-generation sequencing identifies potentially actionable alterations in genes thought to be drivers in the cancerous process including phosphatidylinositol 3-kinase (PI3K), AKT, fibroblast growth factor receptors (FGFRs), and mutant HER2. Epigenetically directed and immunologic therapies have also shown promise for the treatment of breast cancer via histone deacetylases (HDAC) 1 and 3, programmed T cell death 1 (PD-1), and programmed T cell death ligand 1 (PD-L1). Identifying biomarkers to predict primary resistance in breast cancer will ultimately affect clinical decisions regarding adjuvant therapy in the first-line setting. However, the bulk of medical decision-making is currently made in the secondary resistance setting. Herein, we review the clinical potential of PI3K, AKT, FGFRs, mutant HER2, HDAC1/3, PD-1, and PD-L1 as therapeutic targets in breast cancer, focusing on the rationale for therapeutic development and the status of clinical testing. J. Cell. Biochem. 117: 2454-2463, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Major clinical research advances in gynecologic cancer in 2014.

PubMed

Suh, Dong Hoon; Lee, Kyung Hun; Kim, Kidong; Kang, Sokbom; Kim, Jae Weon

2015-04-01

In 2014, 9 topics were selected as major advances in clinical research for gynecologic oncology: 2 each in cervical and corpus cancer, 4 in ovarian cancer, and 1 in breast cancer. For cervical cancer, several therapeutic agents showed viable antitumor clinical response in recurrent and metastatic disease: bevacizumab, cediranib, and immunotherapies including human papillomavirus (HPV)-tumor infiltrating lymphocytes and Z-100. The HPV test received FDA approval as the primary screening tool of cervical cancer in women aged 25 and older, based on the results of the ATHENA trial, which suggested that the HPV test was a more sensitive and efficient strategy for cervical cancer screening than methods based solely on cytology. For corpus cancers, results of a phase III Gynecologic Oncology Group (GOG) 249 study of early-stage endometrial cancer with high-intermediate risk factors are followed by the controversial topic of uterine power morcellation in minimally invasive gynecologic surgery. Promising results of phase II studies regarding the effectiveness of olaparib in various ovarian cancer settings are summarized. After a brief review of results from a phase III study on pazopanib maintenance therapy in advanced ovarian cancer, 2 outstanding 2014 ASCO presentations cover the topic of using molecular subtypes in predicting response to bevacizumab. A review of the use of opportunistic bilateral salpingectomy as an ovarian cancer preventive strategy in the general population is presented. Two remarkable studies that discussed the effectiveness of adjuvant ovarian suppression in premenopausal early breast cancer have been selected as the last topics covered in this review.

Clinical cancer advances 2011: Annual Report on Progress Against Cancer from the American Society of Clinical Oncology.

PubMed

Vogelzang, Nicholas J; Benowitz, Steven I; Adams, Sylvia; Aghajanian, Carol; Chang, Susan Marina; Dreyer, Zoann Eckert; Janne, Pasi A; Ko, Andrew H; Masters, Greg A; Odenike, Olatoyosi; Patel, Jyoti D; Roth, Bruce J; Samlowski, Wolfram E; Seidman, Andrew D; Tap, William D; Temel, Jennifer S; Von Roenn, Jamie H; Kris, Mark G

2012-01-01

A message from ASCO'S President. It has been forty years since President Richard Nixon signed the National Cancer Act of 1971, which many view as the nation's declaration of the "War on Cancer." The bill has led to major investments in cancer research and significant increases in cancer survival. Today, two-thirds of patients survive at least five years after being diagnosed with cancer compared with just half of all diagnosed patients surviving five years after diagnosis in 1975. The research advances detailed in this year's Clinical Cancer Advances demonstrate that improvements in cancer screening, treatment, and prevention save and improve lives. But although much progress has been made, cancer remains one of the world's most serious health problems. In the United States, the disease is expected to become the nation's leading cause of death in the years ahead as our population ages. I believe we can accelerate the pace of progress, provided that everyone involved in cancer care works together to achieve this goal. It is this viewpoint that has shaped the theme for my presidential term: Collaborating to Conquer Cancer. In practice, this means that physicians and researchers must learn from every patient's experience, ensure greater collaboration between members of a patient's medical team, and involve more patients in the search for cures through clinical trials. Cancer advocates, insurers, and government agencies also have important roles to play. Today, we have an incredible opportunity to improve the quality of cancer care by drawing lessons from the real-world experiences of patients. The American Society of Clinical Oncology (ASCO) is taking the lead in this area, in part through innovative use of health information technology. In addition to our existing quality initiatives, ASCO is working with partners to develop a comprehensive rapid-learning system for cancer care. When complete, this system will provide physicians with personalized, real

BRAF Mutations in Advanced Cancers: Clinical Characteristics and Outcomes

PubMed Central

El-Osta, Hazem; Falchook, Gerald; Tsimberidou, Apostolia; Hong, David; Naing, Aung; Kim, Kevin; Wen, Sijin; Janku, Filip; Kurzrock, Razelle

2011-01-01

Background Oncogenic BRAF mutations have been found in diverse malignancies and activate RAF/MEK/ERK signaling, a critical pathway of tumorigenesis. We examined the clinical characteristics and outcomes of patients with mutant (mut) BRAF advanced cancer referred to phase 1 clinic. Methods We reviewed the records of 80 consecutive patients with mutBRAF advanced malignancies and 149 with wild-type (wt) BRAF (matched by tumor type) referred to the Clinical Center for Targeted Therapy and analyzed their outcome. Results Of 80 patients with mutBRAF advanced cancer, 56 had melanoma, 10 colorectal, 11 papillary thyroid, 2 ovarian and 1 esophageal cancer. Mutations in codon 600 were found in 77 patients (62, V600E; 13, V600K; 1, V600R; 1, unreported). Multivariate analysis showed less soft tissue (Odds ratio (OR) = 0.39, 95%CI: 0.20–0.77, P = 0.007), lung (OR = 0.38, 95%CI: 0.19–0.73, p = 0.004) and retroperitoneal metastases (OR = 0.34, 95%CI: 0.13–0.86, p = 0.024) and more brain metastases (OR = 2.05, 95%CI: 1.02–4.11, P = 0.043) in patients with mutBRAF versus wtBRAF. Comparing to the corresponding wtBRAF, mutBRAF melanoma patients had insignificant trend to longer median survival from diagnosis (131 vs. 78 months, p = 0.14), while mutBRAF colorectal cancer patients had an insignificant trend to shorter median survival from diagnosis (48 vs. 53 months, p = 0.22). In melanoma, V600K mutations in comparison to other BRAF mutations were associated with more frequent brain (75% vs. 36.3%, p = 0.02) and lung metastases (91.6% vs. 47.7%, p = 0.007), and shorter time from diagnosis to metastasis and to death (19 vs. 53 months, p = 0.046 and 78 vs. 322 months, p = 0.024 respectively). Treatment with RAF/MEK targeting agents (Hazard ratio (HR) = 0.16, 95%CI: 0.03–0.89, p = 0.037) and any decrease in tumor size after referral (HR = 0.07, 95%CI: 0.015–0.35, p = 0.001) correlated with longer

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

[Application of clinical nursing path integrated with holistic nursing in advanced schistosomiasis patients with ascites].

PubMed

Mei-Zhi, Yuan; Jing-Ru, Sun; Tao, Chen; Xiao-Yu, Zhang; Liang-Cai, He; Jia-Song, Wang

2016-05-12

To evaluate the effect of the clinical nursing path integrated with the holistic nursing on advanced schistosomiasis patients with ascites. A total of 226 advanced schistosomiasis patients with ascites were randomly divided into a control group and an experimental group (113 cases each group). The subjects in the experimental group were nursed by the clinical nursing path integrated with the holistic nursing, while those in the control group were nursed only by the holistic nursing. Then the clinical relevant indexes of the two groups were observed, and the quality of life of the patients before and after hospital discharge was assessed. The improvement rate, satisfaction degree, and awareness rate of health knowledge of the patients in the experiment group were 93.8%, 100% and 97.4%, respectively, which were significantly higher than those of the control group (all P < 0.05). The mortality rate and the complication rate of the patients in the experimental group were 0 and 2.7%, respectively, which were significantly lower than those of the control group (both P < 0.05). In addition, the average hospitalization days and the hospitalization cost of the experiment group were (12.2 ± 0.7) d and (4 725.0 ± 310.1) Yuan respectively, which were less than those of the control group (both P < 0.01). When 6 months after the discharge from hospital, the quality of life of the patients in the experimental group in various fields was significantly better than that of the control group (all P < 0.05). The clinical nursing pathway integrated with holistic nursing can effectively improve the improvement rate and decrease the mortality of the advanced schistosomiasis patients with ascites; meanwhile, it can shorten the hospitalization time and save the hospitalization cost. Therefore, this nursing model is suitable for popularization and application in the treatment and nursing work of the advanced schistosomiasis assistance.

Influence of formulation and processing variables on properties of itraconazole nanoparticles made by advanced evaporative precipitation into aqueous solution.

PubMed

Bosselmann, Stephanie; Nagao, Masao; Chow, Keat T; Williams, Robert O

2012-09-01

Nanoparticles, of the poorly water-soluble drug, itraconazole (ITZ), were produced by the Advanced Evaporative Precipitation into Aqueous Solution process (Advanced EPAS). This process combines emulsion templating and EPAS processing to provide improved control over the size distribution of precipitated particles. Specifically, oil-in-water emulsions containing the drug and suitable stabilizers are sprayed into a heated aqueous solution to induce precipitation of the drug in form of nanoparticles. The influence of processing parameters (temperature and volume of the heated aqueous solution; type of nozzle) and formulation aspects (stabilizer concentrations; total solid concentrations) on the size of suspended ITZ particles, as determined by laser diffraction, was investigated. Furthermore, freeze-dried ITZ nanoparticles were evaluated regarding their morphology, crystallinity, redispersibility, and dissolution behavior. Results indicate that a robust precipitation process was developed such that size distribution of dispersed nanoparticles was shown to be largely independent across the different processing and formulation parameters. Freeze-drying of colloidal dispersions resulted in micron-sized agglomerates composed of spherical, sub-300-nm particles characterized by reduced crystallinity and high ITZ potencies of up to 94% (w/w). The use of sucrose prevented particle agglomeration and resulted in powders that were readily reconstituted and reached high and sustained supersaturation levels upon dissolution in aqueous media.

Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care

Cancer.gov

Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care, a 2010 workshop sponsored by the Epidemiology and Genomics Research Program.

Ten years of iPSC: clinical potential and advances in vitro hematopoietic differentiation.

PubMed

Paes, Bárbara Cristina Martins Fernandes; Moço, Pablo Diego; Pereira, Cristiano Gonçalves; Porto, Geciane Silveira; de Sousa Russo, Elisa Maria; Reis, Luiza Cunha Junqueira; Covas, Dimas Tadeu; Picanço-Castro, Virginia

2017-06-01

Ten years have passed since the first publication announcing the generation of induced pluripotent stem cells (iPSCs). Issues related to ethics, immune rejection, and cell availability seemed to be solved following this breakthrough. The development of iPSC technology allows advances in in vitro cell differentiation for cell therapy purpose and other clinical applications. This review provides a perspective on the iPSC potential for cell therapies, particularly for hematological applications. We discuss the advances in in vitro hematopoietic differentiation, the possibilities to employ iPSC in hematology studies, and their potential clinical application in hematologic diseases. The generation of red blood cells and functional T cells and the genome editing technology applied to mutation correction are also covered. We highlight some of the requirements and obstacles to be overcome before translating these cells from research to the clinic, for instance, iPSC variability, genotoxicity, the differentiation process, and engraftment. Also, we evaluate the patent landscape and compile the clinical trials in the field of pluripotent stem cells. Currently, we know much more about iPSC than in 2006, but there are still challenges that must be solved. A greater understanding of molecular mechanisms underlying the generation of hematopoietic stem cells is necessary to produce suitable and transplantable hematopoietic stem progenitor cells from iPSC.

Technical solutions for mitigating security threats caused by health professionals in clinical settings.

PubMed

Fernandez-Aleman, Jose Luis; Belen Sanchez Garcia, Ana; Garcia-Mateos, Gines; Toval, Ambrosio

2015-08-01

The objective of this paper is to present a brief description of technical solutions for health information system security threats caused by inadequate security and privacy practices in healthcare professionals. A literature search was carried out in ScienceDirect, ACM Digital Library and IEEE Digital Library to find papers reporting technical solutions for certain security problems in information systems used in clinical settings. A total of 17 technical solutions were identified: measures for password security, the secure use of e-mail, the Internet, portable storage devices, printers and screens. Although technical safeguards are essential to the security of healthcare organization's information systems, good training, awareness programs and adopting a proper information security policy are particularly important to prevent insiders from causing security incidents.

World Workshop on Oral Medicine VI: an international validation study of clinical competencies for advanced training in oral medicine.

PubMed

Steele, John C; Clark, Hadleigh J; Hong, Catherine H L; Jurge, Sabine; Muthukrishnan, Arvind; Kerr, A Ross; Wray, David; Prescott-Clements, Linda; Felix, David H; Sollecito, Thomas P

2015-08-01

To explore international consensus for the validation of clinical competencies for advanced training in Oral Medicine. An electronic survey of clinical competencies was designed. The survey was sent to and completed by identified international stakeholders during a 10-week period. To be validated, an individual competency had to achieve 90% or greater consensus to keep it in its current format. Stakeholders from 31 countries responded. High consensus agreement was achieved with 93 of 101 (92%) competencies exceeding the benchmark for agreement. Only 8 warranted further attention and were reviewed by a focus group. No additional competencies were suggested. This is the first international validated study of clinical competencies for advanced training in Oral Medicine. These validated clinical competencies could provide a model for countries developing an advanced training curriculum for Oral Medicine and also inform review of existing curricula. Copyright © 2015 Elsevier Inc. All rights reserved.

The development of leadership outcome-indicators evaluating the contribution of clinical specialists and advanced practitioners to health care: a secondary analysis.

PubMed

Elliott, Naomi; Begley, Cecily; Kleinpell, Ruth; Higgins, Agnes

2014-05-01

To report a secondary analysis of data collected from the case study phase of a national study of advanced practitioners and to develop leadership outcome-indicators appropriate for advanced practitioners. In many countries, advanced practitioners in nursing and midwifery have responsibility as leaders for health care development, but without having leadership outcome measures available they are unable to demonstrate the results of their activities. In Ireland, a sequential mixed method research study was used to develop a validated tool for the evaluation of clinical specialists and advanced practitioners. Despite strong evidence of leadership activities, few leadership-specific outcomes were generated from the primary analysis. Secondary analysis of a multiple case study data set. Data set comprised 23 case studies of advanced practitioner/clinical specialists from 13 sites across each region in Ireland from all divisions of the Nursing Board Register. Data were collected 2008-2010. Data sources included non-participant observation (n = 92 hours) of advanced practitioners in practice, interviews with clinicians (n = 21), patients (n = 20) and directors of nursing/midwifery (n = 13) and documents. Analysis focused on leadership outcome-indicator development in line with the National Health Service's Good Indicators Guide. The four categories of leadership outcomes for advanced practitioner developed were as follows: (i) capacity and capability building of multidisciplinary team; (ii) measure of esteem; (iii) new initiatives for clinical practice and healthcare delivery; and (iv) clinical practice based on evidence. The proposed set of leadership outcome-indicators derived from a secondary analysis captures the complexity of leadership in practice. They add to existing clinical outcomes measuring advanced practice. © 2013 John Wiley & Sons Ltd.

Clinical predictors of advanced sellar masses.

PubMed

Rambaldini, Gloria M; Butalia, Sonia; Ezzat, Shereen; Kucharczyk, Walter; Sawka, Anna M

2007-10-01

To identify clinical variables associated with the presence of a structurally advanced sellar mass (ASM). We performed a retrospective study of patients referred for evaluation of suspected new pituitary disease or sellar mass to the Endocrine Oncology Unit of Mount Sinai Hospital in Toronto, Ontario, Canada. By multivariate analysis, we examined predictors of a structurally ASM (a sellar lesion with any of the following characteristics: diameter of >or=1 cm on magnetic resonance imaging [MRI], optic chiasmal compression on MRI, or clinical or biochemical evidence of hypopituitarism). Data from 152 patients were analyzed. Of the 152 sellar masses, 142 (93%) were pituitary adenomas. An ASM was noted in 85 of the 152 patients (56%). In the final multivariate model, male sex (odds ratio [OR], 6.23; 95% confidence interval [CI], 2.84 to 13.56; P<0.001) and self-reported visual field defect (OR, 3.62; 95% CI, 1.07 to 12.25; P = 0.039) were significantly independently associated with the presence of an ASM. The presence of new or changed headaches also tended to be associated with an ASM (OR, 2.11; 95% CI, 0.96 to 4.64; P = 0.063). Age and self-reported galactorrhea were not independently associated with the presence of an ASM and were conditionally removed from the final model. In patients with suspected sellar or pituitary disease, male sex and self-reported visual field defects independently predict the presence of an ASM. New or changed headaches also tend to be related to the presence of an ASM. The presence of predictors of an ASM should prompt expedited sellar MRI and biochemical evaluation.

Innovation at the Intersection of Clinical Trials and Real-World Data Science to Advance Patient Care.

PubMed

Swift, Brandon; Jain, Lokesh; White, Craig; Chandrasekaran, Vasu; Bhandari, Aman; Hughes, Dyfrig A; Jadhav, Pravin R

2018-05-16

While efficacy and safety data collected from randomized clinical trials are the evidentiary standard for determining market authorization, this alone may no longer be sufficient to address the needs of key stakeholders (regulators, providers, and payers) and guarantee long-term success of pharmaceutical products. There is a heightened interest from stakeholders on understanding the use of real-world evidence (RWE) to substantiate benefit-risk assessment and support the value of a new drug. This review provides an overview of real-world data (RWD) and related advances in the regulatory framework, and discusses their impact on clinical research and development. A framework for linking drug development decisions with the value proposition of the drug, utilizing pharmacokinetic-pharmacodynamic-pharmacoeconomic models, is introduced. The summary presented here is based on the presentations and discussion at the symposium entitled Innovation at the Intersection of Clinical Trials and Real-World Data to Advance Patient Care at the American Society for Clinical Pharmacology and Therapeutics (ASCPT) 2017 Annual Meeting. © 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

The efficacy of self-directed modules for clinical learning: advanced competencies in entry-level physical therapy education.

PubMed

Peck, Kirk; Paschal, Karen; Black, Lisa; Nelson, Kelly

2014-01-01

Prior to graduation, students often express an interest to advance clinical and professional skills in teaching, research, administration, and various niche practice areas. The acquisition of advanced education in selected areas of practice is believed to improve employment opportunities, accelerate career advancement including eligibility for professional certifications, and contribute to personal satisfaction in the profession. The purpose of this paper is to (1) describe an innovative model of education, the Directed Practice Experience (DPE) elective, that incorporates a student-initiated learning process designed to achieve student-identified professional goals, and (2) report the outcomes for graduates who have completed the DPE in an entry-level program in physical therapy education. Students who met select criteria were eligible to complete a DPE. Applicants designed a 4- to 6-week clinical education experience consisting of stated rationale for personal and professional growth, examples of leadership and service, and self-directed objectives that are beyond entry-level expectations as measured by the revised Physical Therapist Clinical Performance Instrument, version 2006. Twenty-six students have completed DPEs since 2005. Fifty percent resulted in new academic partnerships. At least 25% of graduates now serve as clinical instructors for the entry-level program. Those who participated in DPEs have also completed post-graduate residencies, attained ABPTS Board certifications, authored peer-reviewed publications, and taught in both PT and residency programs. The DPE model allows qualified students to acquire advanced personal skills and knowledge prior to graduation in areas of professional practice that exceed entry-level expectations. The model is applicable to all CAPTE accredited physical therapy education programs and is especially beneficial for academic programs desiring to form new community partnerships for student clinical education.

Clinical Application Of Advanced Infrared Thermography (IRT) In Locomotor Diseases

NASA Astrophysics Data System (ADS)

Engel, Joachim-Michael

1983-11-01

Locomotor diseases is a wide range of about 450 different illnesses with all different pathologies, clinical and prognostic features and response to treatment. No single method will be able to cover the whole spectrum of local and systemic signs and symptoms. Nevertheless there is a need for objective measurements at the site of disease: clinical examination is often enough depending from subjective estimations and personal experiance of the clinician. Laboratory tests only show the systemic effect of the disease, like inflammation. X-rays are restricted to the detection of structural changes appearing late during the pathological process, even when using different techniques. Here IRT offers several advantages to the clinician as well as to the patient. As a non invasive method it monitors the course of disease at the anatomic site of pathology. Quantitative figures calculated from the thermogram,either taken at steady-state or during dynamic tests, are essential for differential diagnosis and follow-up. Advanced IRT camera systems fulfill all requirements set up for medical thermography recently by the National Bureau of Standards. Although, the user should check his system daily with regard to precision of absolute temperature measurements. Standardisation of recording technique is essential as well,to get reliable results. Ambient conditions must be adapted to the locomotor disease pathology under study. Advanced IRT systems , e.g. ZEISS-IKOTHERM, together with image processing capability and special software, e.g. THERMOTOM package, are valuable tools to the rheumatologist for diagnosing and monitoring locomotor diseases.

Clinical Advancements in the Targeted Therapies against Liver Fibrosis

PubMed Central

Nagórniewicz, Beata; Prakash, Jai

2016-01-01

Hepatic fibrosis, characterized by excessive accumulation of extracellular matrix (ECM) proteins leading to liver dysfunction, is a growing cause of mortality worldwide. Hepatocellular damage owing to liver injury leads to the release of profibrotic factors from infiltrating inflammatory cells that results in the activation of hepatic stellate cells (HSCs). Upon activation, HSCs undergo characteristic morphological and functional changes and are transformed into proliferative and contractile ECM-producing myofibroblasts. Over recent years, a number of therapeutic strategies have been developed to inhibit hepatocyte apoptosis, inflammatory responses, and HSCs proliferation and activation. Preclinical studies have yielded numerous targets for the development of antifibrotic therapies, some of which have entered clinical trials and showed improved therapeutic efficacy and desirable safety profiles. Furthermore, advancements have been made in the development of noninvasive markers and techniques for the accurate disease assessment and therapy responses. Here, we focus on the clinical developments attained in the field of targeted antifibrotics for the treatment of liver fibrosis, for example, small molecule drugs, antibodies, and targeted drug conjugate. We further briefly highlight different noninvasive diagnostic technologies and will provide an overview about different therapeutic targets, clinical trials, endpoints, and translational efforts that have been made to halt or reverse the progression of liver fibrosis. PMID:27999454

Implementing clinical governance in Isfahan hospitals: Barriers and solutions, 2014.

PubMed

Ferdosi, Masoud; Ziyari, Farhad Bahman; Ollahi, Mehran Nemat; Salmani, Amaneh Rahim; Niknam, Noureddin

2016-01-01

In the new approach, all health care providers have been obligated to maintain and improve the quality and have been accountable for it. One of the ways is the implementation of clinical governance (CG). More accurate understanding of its challenges can help to improve its performance. In this study, barriers of CG implementation are investigated from the perspective of the hospitals involved. Besides, some solutions are suggested based on stakeholders' opinions. This study used combined method (qualitative content analysis and questionnaire) in hospitals affiliated to Isfahan University of Medical Sciences in 2014. First, experts, and stakeholders talked about CG implementation obstacles in a semi-structured interview. Interviews were confirmed by the interviewee (double check). After analyzing the interviews using reduction coding the questionnaire was drawn up. The questionnaire "validity was confirmed by Cronbach's alpha (0/891)" and its reliability was obtained using experts confirmation. Data analyzing was performed using SPSS (18) software. According to results staffing and management factors were the main obstacles. After them, were factors related to organizational culture, infrastructure elements, information, sociocultural and then process factors. The learning barriers were in final rank. Thirty-four solutions was proposed by experts and divided into subset of eight major barriers. Most solutions were offered on modifying processes and minimal solutions about modifying of organizational culture, sociocultural, and educational factors. Removing the obstacles, especially management and human resource factors can be effective by facilitating and accelerating CG. Furthermore, use of experts and stakeholders opinions can help to remove CG barriers.

Dementia and Robotics: People with Advancing Dementia and Their Carers Driving an Exploration into an Engineering Solution to Maintaining Safe Exercise Regimes.

PubMed

Cooper, Carol; Penders, Jacques; Procter, Paula M

2016-01-01

The merging of the human world and the information technology world is advancing at a pace, even for those with dementia there are many useful smart 'phone applications including reminders, family pictures display, GPS functions and video communications. This paper will report upon initial collaborative work developing a robotic solution to engaging individuals with advancing dementia in safe exercise regimes. The research team has been driven by the needs of people with advancing dementia and their carers through a focus group methodology, the format, discussions and outcomes of these groups will be reported. The plans for the next stage of the research will be outlined including the continuing collaboration with advancing dementia and their carers.

Advances in basic and clinical immunology in 2016.

PubMed

Chinen, Javier; Badran, Yousef R; Geha, Raif S; Chou, Janet S; Fried, Ari J

2017-10-01

Advances in basic immunology in 2016 included studies that further characterized the role of different proteins in the differentiation of effector T and B cells, including cytokines and proteins involved in the actin cytoskeleton. Regulation of granule formation and secretion in cytotoxic cells was also further described by examining patients with familial hemophagocytic lymphohistiocytosis. The role of prenylation in patients with mevalonate kinase deficiency leading to inflammation has been established. We reviewed advances in clinical immunology, as well as new approaches of whole-genome sequencing and genes newly reported to be associated with immunodeficiency, such as linker of activation of T cells (LAT); B-cell CLL/lymphoma 11B (BCL11B); RGD, leucine-rich repeat, tropomodulin domain, and proline-rich domain-containing protein (RLTPR); moesin; and Janus kinase 1 (JAK1). Trials of hematopoietic stem cell transplantation and gene therapy for primary immunodeficiency have had relative success; the use of autologous virus-specific cytotoxic T cells has proved effective as well. New medications are being explored, such as pioglitazone, which is under study for its role in enhancing the oxidative burst in patients with chronic granulomatous disease. Development of vaccines for HIV infection continues to provide insight into the immune response against a virus with an extraordinary mutation rate. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Comparative Clinical Efficacy between Electrodesiccation with Curettage and Application of 80% Phenol Solution in Treatment of Common Warts

PubMed Central

Dalimunthe, Dina Arwina; Siregar, Remenda; Tanjung, Chairiyah

2018-01-01

BACKGROUND: Common warts are skin diseases caused by human papillomavirus. Several treatment modalities available for common warts, two of them are electrodesiccation with curettage and application of 80% phenol solution. AIM: This study aims to compare clinical efficacy between these two modalities. MATERIAL AND METHODS: Open clinical trial was conducted at Dr Pirngadi General Hospital Medan and H. Adam Malik General Hospital Medan from February to June 2013 on 17 patients with multiple common warts. Both treatments began and applied simultaneously on the same day on each patient. RESULTS: Cure rate was higher in electrodesiccation with curettage (76.5%, 100%) compared to the application of 80% phenol solution (11.8%, 64.7%) on three weeks and six weeks of follow up. Statistical analysis showed a significant difference of common warts cure rate between electrodesiccation with curettage and application of 80% phenol solution after three weeks (p < 0.001) and six weeks (p = 0.018) of treatment. CONCLUSION: As a conclusion, electrodesiccation with curettage has higher cure rate than the application of 80% phenol solution on the treatment of common warts. Further study is needed to find out the best concentration and time interval for application of phenol solution to improve its clinical efficacy as an alternative treatment of choice for common warts. PMID:29531597

Clinically relevant advances in on-chip affinity-based electrophoresis and electrochromatography.

PubMed

Hou, Chenlu; Herr, Amy E

2008-08-01

Clinical and point-of-care disease diagnostics promise to play an important role in personalized medicine, new approaches to global health, and health monitoring. Emerging instrument platforms based on lab-on-a-chip technology can confer performance advantages successfully exploited in electrophoresis and electrochromatography to affinity-based electrokinetic separations. This review surveys lab-on-a-chip diagnostic developments in affinity-based electrokinetic separations for quantitation of proteins, integration of preparatory functions needed for subsequent analysis of diverse biological samples, and initial forays into multiplexed analyses. The technologies detailed here underpin new clinical and point-of-care diagnostic strategies. The techniques and devices promise to advance translation of until now laboratory-based sample preparation and analytical assays to near-patient settings.

Echocardiography and risk prediction in advanced heart failure: incremental value over clinical markers.

PubMed

Agha, Syed A; Kalogeropoulos, Andreas P; Shih, Jeffrey; Georgiopoulou, Vasiliki V; Giamouzis, Grigorios; Anarado, Perry; Mangalat, Deepa; Hussain, Imad; Book, Wendy; Laskar, Sonjoy; Smith, Andrew L; Martin, Randolph; Butler, Javed

2009-09-01

Incremental value of echocardiography over clinical parameters for outcome prediction in advanced heart failure (HF) is not well established. We evaluated 223 patients with advanced HF receiving optimal therapy (91.9% angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, 92.8% beta-blockers, 71.8% biventricular pacemaker, and/or defibrillator use). The Seattle Heart Failure Model (SHFM) was used as the reference clinical risk prediction scheme. The incremental value of echocardiographic parameters for event prediction (death or urgent heart transplantation) was measured by the improvement in fit and discrimination achieved by addition of standard echocardiographic parameters to the SHFM. After a median follow-up of 2.4 years, there were 38 (17.0%) events (35 deaths; 3 urgent transplants). The SHFM had likelihood ratio (LR) chi(2) 32.0 and C statistic 0.756 for event prediction. Left ventricular end-systolic volume, stroke volume, and severe tricuspid regurgitation were independent echocardiographic predictors of events. The addition of these parameters to SHFM improved LR chi(2) to 72.0 and C statistic to 0.866 (P < .001 and P=.019, respectively). Reclassifying the SHFM-predicted risk with use of the echocardiography-added model resulted in improved prognostic separation. Addition of standard echocardiographic variables to the SHFM results in significant improvement in risk prediction for patients with advanced HF.

Geometric analysis of the V-Y advancement flap and its clinical applications.

PubMed

Andrades, Patricio R; Calderon, Wilfredo; Leniz, Patricio; Bartel, German; Danilla, Stefan; Benitez, Susana

2005-05-01

Geometry is fundamental in the comprehension of local flap design. The purpose of this study was to discuss the differences between the V-Y advancement flap and other local flaps, understand its geometry, and analyze its clinical applications. The analysis was based on qualitative measurements of an injury, taking into consideration the following dimensions: largest diameter, shortest diameter, and depth. Standardization of the flap design consisted of directing its advancement over the shortest diameter and making the V base match the size of the largest diameter. The flap was analyzed in two planes: the horizontal plane includes the V-Y design and the vertical plane includes the flap pedicle. The height of the flap can be obtained by simple trigonometry, taking into consideration the largest diameter and alpha angle in the horizontal plane. In the vertical plane, where the pedicle and pivot plane are positioned, for known shortest diameter and depth, the final depth of the pivot plane can be calculated using Pythagoras' principles. This analysis was applied to 25 patients with adequate skin coverage at follow-up. A correction factor was added to reduce the overdeepening of the vertical plane calculations. The final concepts for clinical application in the classic deep pedicle V-Y flap design are to calculate the length of the V by modifying the alpha angle and to move the pivot plane deeper to accomplish optimal flap movement. Using these principles, tension-free closure of the Y and appropriate advancement of the flap are obtained.

Developing a clinical trial unit to advance research in an academic institution.

PubMed

Croghan, Ivana T; Viker, Steven D; Limper, Andrew H; Evans, Tamara K; Cornell, Alissa R; Ebbert, Jon O; Gertz, Morie A

2015-11-01

Research, clinical care, and education are the three cornerstones of academic health centers in the United States. The research climate has always been riddled with ebbs and flows, depending on funding availability. During a time of reduced funding, the number and scope of research studies have been reduced, and in some instances, a field of study has been eliminated. Recent reductions in the research funding landscape have led institutions to explore new ways to continue supporting research. Mayo Clinic in Rochester, MN has developed a clinical trial unit within the Department of Medicine, which provides shared resources for many researchers and serves as a solution for training and mentoring new investigators and study teams. By building on existing infrastructure and providing supplemental resources to existing research, the Department of Medicine clinical trial unit has evolved into an effective mechanism for conducting research. This article discusses the creation of a central unit to provide research support in clinical trials and presents the advantages, disadvantages, and required building blocks for such a unit. Copyright © 2015 Mayo Clinic. Published by Elsevier Inc. All rights reserved.

Advances in quantitative UV-visible spectroscopy for clinical and pre-clinical application in cancer.

PubMed

Brown, J Quincy; Vishwanath, Karthik; Palmer, Gregory M; Ramanujam, Nirmala

2009-02-01

Methods of optical spectroscopy that provide quantitative, physically or physiologically meaningful measures of tissue properties are an attractive tool for the study, diagnosis, prognosis, and treatment of various cancers. Recent development of methodologies to convert measured reflectance and fluorescence spectra from tissue to cancer-relevant parameters such as vascular volume, oxygenation, extracellular matrix extent, metabolic redox states, and cellular proliferation have significantly advanced the field of tissue optical spectroscopy. The number of publications reporting quantitative tissue spectroscopy results in the UV-visible wavelength range has increased sharply in the past three years, and includes new and emerging studies that correlate optically measured parameters with independent measures such as immunohistochemistry, which should aid in increased clinical acceptance of these technologies.

Professional excellence and career advancement in nursing: a conceptual framework for clinical leadership development.

PubMed

Adeniran, Rita Kudirat; Bhattacharya, Anand; Adeniran, Anthony A

2012-01-01

Increasingly, stakeholders in the health care community are recognizing nursing as key to solving the nation's health care issues. This acknowledgment provides a unique opportunity for nursing to demonstrate leadership by developing clinical nurse leaders to collaborate with the multidisciplinary care team in driving evidence-based, safe quality, cost-effective health care services. One approach for nursing success is standardizing the entry-level education for nurses and developing a uniform professional development and career advancement trajectory with appropriate incentives to encourage participation. A framework to guide and provide scientific evidence of how frontline nurses can be engaged will be paramount. The model for professional excellence and career advancement provides a framework that offers a clear path for researchers to examine variables influencing nurses' professional development and career advancement in a systematic manner. Professional Excellence and Career Advancement in Nursing underscores professional preparedness of a registered nurse as central to leadership development. It also describes the elements that influence nurses' participation in professional development and career advancement under 4 main categories emphasizing mentorship and self-efficacy as essential variables.

[Clinical effects for patients with recurrent advanced non-small cell lung cancer treated with icotinib hydrochloride].

PubMed

Nong, Jingying; Qin, Na; Wang, Jinghui; Yang, Xinjie; Zhang, Hui; Wu, Yuhua; Lv, Jialin; Zhang, Quan; Zhang, Shucai

2013-05-01

Icotinib hydrochloride is the third single target EGFR-TKI used in clinical treatment of advanced non-small cell lung cancer (NSCLC). Clinical research reports on its efficacy and survival in patients with Recurrent Advanced NSCLC are still little.The aim of this study is to evaluate the efficacy and survival of Icotinib hydrochloride for patients with advanced non-small cell lung cancer who failed to previous chemotherapy and explore the association of clinical features with the efficacy and survival. The clinical data of 60 NSCLC patients referred to the Beijing Chest Hospital, Capital Medical University from March 2009 to July 2012 were retrospectively analyzed. The overall response rate (ORR) was 45.0% and the disease control rate (DCR) was 80.0%. The median progression-free survival (PFS) time was 6.7 months. RR and PFS in female were superior to male (P=0.014, 0.013, respectively). RR, DCR in 2nd-line subgroup were superior to ≥3rd-line subgroup (P=0.020, 0.024, respectively). RR, DCR and PFS in EGFR mutation carriers were significantly superior to wild-type patients (P=0.006, <0.001, 0.002, respectively). There was no statistical difference in RR and PFS between those age<65 and ≥65 or PS<2 and PS≥2. There was no statistical difference in RR and DCR between exon 19 deletion and exon 21 mutations, while the former had much longer PFS (P=0.020). EGFR mutation and exon 19 deletion are the independent prognostic factors to significantly improve the PFS (P=0.009, 0.012, respectively). The side effects were generally mild and consisted of rash and diarrhea. Icotinib hydrochloride is effective especially in EGFR mutation carriers and well tolerated in patients with recurrent advanced non-small-cell lung cancer.

Translational Radiomics: Defining the Strategy Pipeline and Considerations for Application-Part 2: From Clinical Implementation to Enterprise.

PubMed

Shaikh, Faiq; Franc, Benjamin; Allen, Erastus; Sala, Evis; Awan, Omer; Hendrata, Kenneth; Halabi, Safwan; Mohiuddin, Sohaib; Malik, Sana; Hadley, Dexter; Shrestha, Rasu

2018-03-01

Enterprise imaging has channeled various technological innovations to the field of clinical radiology, ranging from advanced imaging equipment and postacquisition iterative reconstruction tools to image analysis and computer-aided detection tools. More recently, the advancement in the field of quantitative image analysis coupled with machine learning-based data analytics, classification, and integration has ushered in the era of radiomics, a paradigm shift that holds tremendous potential in clinical decision support as well as drug discovery. However, there are important issues to consider to incorporate radiomics into a clinically applicable system and a commercially viable solution. In this two-part series, we offer insights into the development of the translational pipeline for radiomics from methodology to clinical implementation (Part 1) and from that point to enterprise development (Part 2). In Part 2 of this two-part series, we study the components of the strategy pipeline, from clinical implementation to building enterprise solutions. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Advance provision of emergency contraception to young men: An exploratory study in a clinic setting.

PubMed

Garbers, Samantha; Bell, D L; Ogaye, K; Marcell, A V; Westhoff, C L; Rosenthal, S L

2018-04-17

To explore the acceptability of advance provision of emergency contraceptive pills (ECPs) to young men seeking health care. For this exploratory study in a clinic setting, we approached young men aged 16-35 to participate in a survey eliciting socio-demographics, sexual and contraceptive history, and knowledge about ECPs. We offered young men advance provision of ECPs and compared characteristics of 126 young men who did and did not accept the ECPs. Most (76%) of the participants accepted advance provision and left with an ECP pack, with even higher proportions among males whose sexual histories were suggestive of increased risk of involvement in an unintended pregnancy. This study holds promise to inform scale up of advance provision of ECPs among young men. Copyright © 2018 Elsevier Inc. All rights reserved.

Translational genetics: advancing fronts for craniofacial health.

PubMed

D'Souza, R N; Dunnwald, M; Dunnvald, M; Frazier-Bowers, S; Polverini, P J; Wright, J T; de Rouen, T; Vieira, A R

2013-12-01

Scientific opportunities have never been better than today! The completion of the Human Genome project has sparked hope and optimism that cures for debilitating conditions can be achieved and tailored to individuals and communities. The availability of reference genome sequences and genetic variations as well as more precise correlations between genotype and phenotype have facilitated the progress made in finding solutions to clinical problems. While certain craniofacial and oral diseases previously deemed too difficult to tackle have benefited from basic science and technological advances over the past decade, there remains a critical need to translate the fruits of several decades' worth of basic and clinical research into tangible therapies that can benefit patients. The fifth Annual Fall Focused Symposium, "Translational Genetics - Advancing Fronts for Craniofacial Health", was created by the American Association for Dental Research (AADR) to foster its mission to advance interdisciplinary research that is directed toward improving oral health. The symposium showcased progress made in identifying molecular targets that are potential therapeutics for common and rare dental diseases and craniofacial disorders. Speakers focused on translational and clinical applications of their research and, where applicable, on strategies for new technologies and therapeutics. The critical needs to transfer new knowledge to the classroom and for further investment in the field were also emphasized. The symposium underscored the importance of basic research, chairside clinical observations, and population-based studies in driving the new translational connections needed for the development of cures for the most common and devastating diseases involving the craniofacial complex.

Contact lens disinfecting solutions antibacterial efficacy: comparison between clinical isolates and the standard ISO ATCC strains of Pseudomonas aeruginosa and Staphylococcus aureus.

PubMed

Mohammadinia, M; Rahmani, S; Eslami, G; Ghassemi-Broumand, M; Aghazadh Amiri, M; Aghaie, Gh; Tabatabaee, S M; Taheri, S; Behgozin, A

2012-02-01

To evaluate the disinfectant properties of the three multipurpose contact lens disinfecting solutions available in Iran, against clinical isolates and the standard ISO ATCC strains of Pseudomonas aeruginosa and Staphylococcus aureus, based on the international organization for standardization (ISO) 14729 guidelines. Three multipurpose solutions that were tested were ReNu Multiplus, Solo Care Aqua and All-Clean Soft. The test solutions were challenged with clinical isolates and the standard strains of P. aeruginosa(ATCC 9027) and S. aureus(ATCC 6538), based on the ISO Stand-alone procedure for disinfecting products. Solutions were sampled for surviving microorganisms at manufacturer's minimum recommended disinfection time. The number of viable organisms was determined and log reductions calculated. All of the three test solutions in this study provided a reduction greater than the required mean 3.0 logarithmic reduction against the recommended standard ATCC strains of P. aeruginosa and S. aureus. Antibacterial effectiveness of Solo Care Aqua and All-Clean Soft against clinical isolates of P. aeruginosa and S. aureus were acceptable based on ISO 14729 Stand-alone test. ReNu MultiPlus showed a minimum acceptable efficacy against the clinical isolate of S. aureus, but did not reduce the clinical isolate by the same amount. Although the contact lens disinfecting solutions meet/exceed the ISO 14729 Stand-alone primary acceptance criteria for standard strains of P. aeruginosa and S. aureus, their efficacy may be insufficient against clinical isolates of these organisms.

Contact lens disinfecting solutions antibacterial efficacy: comparison between clinical isolates and the standard ISO ATCC strains of Pseudomonas aeruginosa and Staphylococcus aureus

PubMed Central

Mohammadinia, M; Rahmani, S; Eslami, G; Ghassemi-Broumand, M; Aghazadh Amiri, M; Aghaie, Gh; Tabatabaee, S M; Taheri, S; Behgozin, A

2012-01-01

Purpose To evaluate the disinfectant properties of the three multipurpose contact lens disinfecting solutions available in Iran, against clinical isolates and the standard ISO ATCC strains of Pseudomonas aeruginosaand Staphylococcus aureus, based on the international organization for standardization (ISO) 14729 guidelines. Methods Three multipurpose solutions that were tested were ReNu Multiplus, Solo Care Aqua and All-Clean Soft. The test solutions were challenged with clinical isolates and the standard strains of P. aeruginosa(ATCC 9027) and S. aureus(ATCC 6538), based on the ISO Stand-alone procedure for disinfecting products. Solutions were sampled for surviving microorganisms at manufacturer's minimum recommended disinfection time. The number of viable organisms was determined and log reductions calculated. Results All of the three test solutions in this study provided a reduction greater than the required mean 3.0 logarithmic reduction against the recommended standard ATCC strains of P. aeruginosaand S. aureus. Antibacterial effectiveness of Solo Care Aqua and All-Clean Soft against clinical isolates of P. aeruginosaand S. aureuswere acceptable based on ISO 14729 Stand-alone test. ReNu MultiPlus showed a minimum acceptable efficacy against the clinical isolate of S. aureus, but did not reduce the clinical isolate by the same amount. Conclusions Although the contact lens disinfecting solutions meet/exceed the ISO 14729 Stand-alone primary acceptance criteria for standard strains of P. aeruginosaand S. aureus, their efficacy may be insufficient against clinical isolates of these organisms. PMID:22094301

Engineering and clinical-oriented solution to cost-effective PACS for developing areas in China

NASA Astrophysics Data System (ADS)

Hu, Dake; Zhang, Hong; Zhou, Shengmin; Shao, Lin

1997-05-01

Although PACS has been studied in industrial countries for more than sixteen years, few effort has been made so far to apply PACS technology to such developing areas as most rural regions in CHina. Engineering and clinical problems raised from installing PACS in undeveloped areas has brought many challenges to our system design. In this study, we try to analyze the clinical need of the Chinese hospitals and find out a solution to meet most hospitals' requirements from engineering and clinical points of view, such as system cost, ease of deployment, user interface, maintenance difficulty, etc., thus provide patients with better medical serve at affordable cost. First of all, we analyzed data collected from Zhejiang Cancer Hospital (ZCH) and take hospitals' financial situation into consideration. then according to the analysis, we made our choices for hardware and software platform, digitizer and storage device. The development of mini PACS is interacted by clinicians and radiologists from ZCH. They showed great interest in the downsizing PACS that does not risk much of the system performance. It is promising that our solution will be accepted in developing areas.

Solution-based circuits enable rapid and multiplexed pathogen detection.

PubMed

Lam, Brian; Das, Jagotamoy; Holmes, Richard D; Live, Ludovic; Sage, Andrew; Sargent, Edward H; Kelley, Shana O

2013-01-01

Electronic readout of markers of disease provides compelling simplicity, sensitivity and specificity in the detection of small panels of biomarkers in clinical samples; however, the most important emerging tests for disease, such as infectious disease speciation and antibiotic-resistance profiling, will need to interrogate samples for many dozens of biomarkers. Electronic readout of large panels of markers has been hampered by the difficulty of addressing large arrays of electrode-based sensors on inexpensive platforms. Here we report a new concept--solution-based circuits formed on chip--that makes highly multiplexed electrochemical sensing feasible on passive chips. The solution-based circuits switch the information-carrying signal readout channels and eliminate all measurable crosstalk from adjacent, biomolecule-specific microsensors. We build chips that feature this advance and prove that they analyse unpurified samples successfully, and accurately classify pathogens at clinically relevant concentrations. We also show that signature molecules can be accurately read 2  minutes after sample introduction.

New clinical trial explores precision treatment for advanced pancreatic cancer | Center for Cancer Research

Cancer.gov

A new phase II clinical trial to assess the safety and efficacy of a drug called selumetinib for treating patients with advanced pancreatic cancer whose tumors harbor a specific genetic marker has opened at the Center for Cancer Research and is currently recruiting participants. Read more...

Advanced ensemble modelling of flexible macromolecules using X-ray solution scattering.

PubMed

Tria, Giancarlo; Mertens, Haydyn D T; Kachala, Michael; Svergun, Dmitri I

2015-03-01

Dynamic ensembles of macromolecules mediate essential processes in biology. Understanding the mechanisms driving the function and molecular interactions of 'unstructured' and flexible molecules requires alternative approaches to those traditionally employed in structural biology. Small-angle X-ray scattering (SAXS) is an established method for structural characterization of biological macromolecules in solution, and is directly applicable to the study of flexible systems such as intrinsically disordered proteins and multi-domain proteins with unstructured regions. The Ensemble Optimization Method (EOM) [Bernadó et al. (2007 ▶). J. Am. Chem. Soc. 129, 5656-5664] was the first approach introducing the concept of ensemble fitting of the SAXS data from flexible systems. In this approach, a large pool of macromolecules covering the available conformational space is generated and a sub-ensemble of conformers coexisting in solution is selected guided by the fit to the experimental SAXS data. This paper presents a series of new developments and advancements to the method, including significantly enhanced functionality and also quantitative metrics for the characterization of the results. Building on the original concept of ensemble optimization, the algorithms for pool generation have been redesigned to allow for the construction of partially or completely symmetric oligomeric models, and the selection procedure was improved to refine the size of the ensemble. Quantitative measures of the flexibility of the system studied, based on the characteristic integral parameters of the selected ensemble, are introduced. These improvements are implemented in the new EOM version 2.0, and the capabilities as well as inherent limitations of the ensemble approach in SAXS, and of EOM 2.0 in particular, are discussed.

From Unmet Clinical Need to Entrepreneurship: Taking Your Informatics Solution to Market

PubMed Central

Bowles, Kathryn H.; Heil, Eric

2015-01-01

This paper will describe the process for taking a decision support solution to market as a start-up business. The nurse inventor and Co-Founder of RightCare Solutions, Inc. will share the steps from answering a clinical question, to registering an invention, creating a business plan and company, obtaining venture funding, and launching a commercial product. We will share positives about the experience such as how to get start-up funds, gaining national exposure and access to an excellent team, disseminating your work broadly, further enhancing the product, and obtaining equity, and financial rewards. We will discuss cons such as losing control, dilution of ownership, and conflict of interest. This paper will encourage nurse informaticians to think differently and learn about the steps in the process from an experienced team. PMID:24943561

From unmet clinical need to entrepreneurship: taking your informatics solution to market.

PubMed

Bowles, Kathryn H; Heil, Eric

2014-01-01

This paper will describe the process for taking a decision support solution to market as a start-up business. The nurse inventor and Co-Founder of RightCare Solutions, Inc. will share the steps from answering a clinical question, to registering an invention, creating a business plan and company, obtaining venture funding, and launching a commercial product. We will share positives about the experience such as how to get start-up funds, gaining national exposure and access to an excellent team, disseminating your work broadly, further enhancing the product, and obtaining equity, and financial rewards. We will discuss cons such as losing control, dilution of ownership, and conflict of interest. This paper will encourage nurse informaticians to think differently and learn about the steps in the process from an experienced team.

Biology of advanced uveal melanoma and next steps for clinical therapeutics.

PubMed

Luke, Jason J; Triozzi, Pierre L; McKenna, Kyle C; Van Meir, Erwin G; Gershenwald, Jeffrey E; Bastian, Boris C; Gutkind, J Silvio; Bowcock, Anne M; Streicher, Howard Z; Patel, Poulam M; Sato, Takami; Sossman, Jeffery A; Sznol, Mario; Welch, Jack; Thurin, Magdalena; Selig, Sara; Flaherty, Keith T; Carvajal, Richard D

2015-03-01

Uveal melanoma is the most common intraocular malignancy although it is a rare subset of all melanomas. Uveal melanoma has distinct biology relative to cutaneous melanoma, with widely divergent patient outcomes. Patients diagnosed with a primary uveal melanoma can be stratified for risk of metastasis by cytogenetics or gene expression profiling, with approximately half of patients developing metastatic disease, predominately hepatic in location, over a 15-yr period. Historically, no systemic therapy has been associated with a clear clinical benefit for patients with advanced disease, and median survival remains poor. Here, as a joint effort between the Melanoma Research Foundation's ocular melanoma initiative, CURE OM and the National Cancer Institute, the current understanding of the molecular and immunobiology of uveal melanoma is reviewed, and on-going laboratory research into the disease is highlighted. Finally, recent investigations relevant to clinical management via targeted and immunotherapies are reviewed, and next steps in the development of clinical therapeutics are discussed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Photography in Dermatologic Surgery: Selection of an Appropriate Lighting Solution for a Particular Clinical Application.

PubMed

Chen, Brian R; Poon, Emily; Alam, Murad

2018-01-01

Lighting is an important component of consistent, high-quality dermatologic photography. There are different types of lighting solutions available. To evaluate currently available lighting equipment and methods suitable for procedural dermatology. Overhead lighting, built-in camera flashes, external flash units, studio strobes, and light-emitting diode (LED) light panels were evaluated with regard to their utility for dermatologic surgeons. A set of ideal lighting characteristics was used to examine the capabilities and limitations of each type of lighting solution. Recommendations regarding lighting solutions and optimal usage configurations were made in terms of the context of the clinical environment and the purpose of the image. Overhead lighting may be a convenient option for general documentation. An on-camera lighting solution using a built-in camera flash or a camera-mounted external flash unit provides portability and consistent lighting with minimal training. An off-camera lighting solution with studio strobes, external flash units, or LED light panels provides versatility and even lighting with minimal shadows and glare. The selection of an optimal lighting solution is contingent on practical considerations and the purpose of the image.

Clinical cancer advances 2008: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

PubMed

Winer, Eric; Gralow, Julie; Diller, Lisa; Karlan, Beth; Loehrer, Patrick; Pierce, Lori; Demetri, George; Ganz, Patricia; Kramer, Barnett; Kris, Mark; Markman, Maurie; Mayer, Robert; Pfister, David; Raghavan, Derek; Ramsey, Scott; Reaman, Gregory; Sandler, Howard; Sawaya, Raymond; Schuchter, Lynn; Sweetenham, John; Vahdat, Linda; Schilsky, Richard L

2009-02-10

significant clinical research is conducted increasingly overseas. In addition, talented young physicians in the United States, seeing less opportunity in the field of oncology, are choosing other specialties instead. Although greater investment in research is critical, the need for new therapies is only part of the challenge. Far too many people in the United States lack access to the treatments that already exist, leading to unnecessary suffering and death. Uninsured cancer patients are significantly more likely to die than those with insurance, racial disparities in cancer incidence and mortality remain stark, and even insured patients struggle to keep up with the rapidly rising cost of cancer therapies. As this annual American Society of Clinical Oncology report of the major cancer research advances during the last year demonstrates, we are making important progress against cancer. But sound public policies are essential to accelerate that progress. In 2009, we have an opportunity to reinvest in cancer research, and to support policies that will help ensure that every individual in the United States receives potentially life-saving cancer prevention, early detection, and treatment. Sincerely, Richard L. Schilsky, MD President American Society of Clinical Oncology.

Advance Care Planning: Understanding Clinical Routines and Experiences of Interprofessional Team Members in Diverse Health Care Settings.

PubMed

Arnett, Kelly; Sudore, Rebecca L; Nowels, David; Feng, Cindy X; Levy, Cari R; Lum, Hillary D

2017-12-01

Interprofessional health care team members consider advance care planning (ACP) to be important, yet gaps remain in systematic clinical routines to support ACP. A clearer understanding of the interprofessional team members' perspectives on ACP clinical routines in diverse settings is needed. One hundred eighteen health care team members from community-based clinics, long-term care facilities, academic clinics, federally qualified health centers, and hospitals participated in a 35-question, cross-sectional online survey to assess clinical routines, workflow processes, and policies relating to ACP. Respondents were 53% physicians, 18% advanced practice nurses, 11% nurses, and 18% other interprofessional team members including administrators, chaplains, social workers, and others. Regarding clinical routines, respondents reported that several interprofessional team members play a role in facilitating ACP (ie, physician, social worker, nurse, others). Most (62%) settings did not have, or did not know of, policies related to ACP documentation. Only 14% of settings had a patient education program. Two-thirds of the respondents said that addressing ACP is a high priority and 85% felt that nonphysicians could have ACP conversations with appropriate training. The clinical resources needed to improve clinical routines included training for providers and staff, dedicated staff to facilitate ACP, and availability of patient/family educational materials. Although interprofessional health care team members consider ACP a priority and several team members may be involved, clinical settings lack systematic clinical routines to support ACP. Patient educational materials, interprofessional team training, and policies to support ACP clinical workflows that do not rely solely on physicians could improve ACP across diverse clinical settings.

Recent theoretical, neural, and clinical advances in sustained attention research.

PubMed

Fortenbaugh, Francesca C; DeGutis, Joseph; Esterman, Michael

2017-05-01

Models of attention often distinguish among attention subtypes, with classic models separating orienting, switching, and sustaining functions. Compared with other forms of attention, the neurophysiological basis of sustaining attention has received far less notice, yet it is known that momentary failures of sustained attention can have far-ranging negative effects in healthy individuals, and lasting sustained attention deficits are pervasive in clinical populations. In recent years, however, there has been increased interest in characterizing moment-to-moment fluctuations in sustained attention, in addition to the overall vigilance decrement, and understanding how these neurocognitive systems change over the life span and across various clinical populations. The use of novel neuroimaging paradigms and statistical approaches has allowed for better characterization of the neural networks supporting sustained attention and has highlighted dynamic interactions within and across multiple distributed networks that predict behavioral performance. These advances have also provided potential biomarkers to identify individuals with sustained attention deficits. These findings have led to new theoretical models explaining why sustaining focused attention is a challenge for individuals and form the basis for the next generation of sustained attention research, which seeks to accurately diagnose and develop theoretically driven treatments for sustained attention deficits that affect a variety of clinical populations. © 2017 New York Academy of Sciences.

Recent theoretical, neural, and clinical advances in sustained attention research

PubMed Central

Fortenbaugh, Francesca C.; DeGutis, Joseph; Esterman, Michael

2017-01-01

Models of attention often distinguish between attention subtypes, with classic models separating orienting, switching, and sustaining functions. Compared to other forms of attention, the neurophysiological basis of sustaining attention has received far less attention yet it is known that momentary failures of sustained attention can have far ranging negative impacts in healthy individuals and lasting sustained attention deficits are pervasive in clinical populations. In recent years, however, there has been increased interest in characterizing moment-to-moment fluctuations in sustained attention in addition to the overall vigilance decrement and understanding how these neurocognitive systems change over the lifespan and across various clinical populations. The use of novel neuroimaging paradigms and statistical approaches has allowed for better characterization of the neural networks supporting sustained attention, and highlighted dynamic interactions within and across multiple distributed networks that predict behavioral performance. These advances have also provided potential biomarkers to identify individuals with sustained attention deficits. These findings have led to new theoretical models of why sustaining focused attention is a challenge for individuals and form the basis for the next generation of sustained attention research, which seeks to accurately diagnose and develop theoretically-driven treatments for sustained attention deficits that affect a variety of clinical populations. PMID:28260249

Major clinical research advances in gynecologic cancer in 2017.

PubMed

Suh, Dong Hoon; Kim, Miseon; Lee, Kyung Hun; Eom, Keun Yong; Kjeldsen, Maj Kamille; Mirza, Mansoor Raza; Kim, Jae Weon

2018-03-01

In 2017, 10 topics were selected as major clinical research advances in gynecologic oncology. For cervical cancer, efficacy and safety analysis results of a 9-valent human papillomavirus (HPV) vaccine and long-term impact of reduced dose of quadrivalent vaccine were updated. Brief introduction of KEYNOTE trials of pembrolizumab, a monoclonal antibody that blocks the interaction between programmed death (PD)-1 and its ligands, PD-L1 and PD-L2, followed. Tailored surveillance programs for gynecologic cancer related with Lynch syndrome and update on sentinel lymph node mapping were reviewed for uterine corpus cancer. For ovarian cancer, 5 topics were selected including poly(ADP-ribose) polymerases inhibitors and immunotherapy. The other potential practice changers covered in this review were lymphadenectomy in advanced disease, secondary cytoreductive surgery in recurrent disease, weekly dose-dense regimen for first-line chemotherapy, incorporation of bevacizumab maintenance in platinum-sensitive recurrent disease, and effect of platinum-free interval prolongation. Conflicting opinions of academic societies on periodic pelvic examination were introduced in conjunction with relevant literature review. For the field of radiation oncology, results of 2 big trials, The Postoperative Radiation Therapy in Endometrial Carcinoma-3 and Gynecologic Oncology Group-258, for endometrial cancer and recent advance in high-dose-rate brachytherapy for cervical cancer were reported. Topics for breast cancer covered adjuvant capecitabine after preoperative chemotherapy, adjuvant pertuzumab and trastuzumab in early human epidermal growth factor receptor 2-positive disease, olaparib for metastatic cancer in patients with a germline BRCA mutation, 20-year risks of recurrence after stopping endocrine therapy at 5 years, and contemporary hormonal contraception and the risk of breast cancer. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

Fostering clinical reasoning in physiotherapy: comparing the effects of concept map study and concept map completion after example study in novice and advanced learners.

PubMed

Montpetit-Tourangeau, Katherine; Dyer, Joseph-Omer; Hudon, Anne; Windsor, Monica; Charlin, Bernard; Mamede, Sílvia; van Gog, Tamara

2017-12-01

Health profession learners can foster clinical reasoning by studying worked examples presenting fully worked out solutions to a clinical problem. It is possible to improve the learning effect of these worked examples by combining them with other learning activities based on concept maps. This study investigated which combinaison of activities, worked examples study with concept map completion or worked examples study with concept map study, fosters more meaningful learning of intervention knowledge in physiotherapy students. Moreover, this study compared the learning effects of these learning activity combinations between novice and advanced learners. Sixty-one second-year physiotherapy students participated in the study which included a pre-test phase, a 130-min guided-learning phase and a four-week self-study phase. During the guided and self-study learning sessions, participants had to study three written worked examples presenting the clinical reasoning for selecting electrotherapeutic currents to treat patients with motor deficits. After each example, participants engaged in either concept map completion or concept map study depending on which learning condition they were randomly allocated to. Students participated in an immediate post-test at the end of the guided-learning phase and a delayed post-test at the end of the self-study phase. Post-tests assessed the understanding of principles governing the domain of knowledge to be learned (conceptual knowledge) and the ability to solve new problems that have similar (i.e., near transfer) or different (i.e., far transfer) solution rationales as problems previously studied in the examples. Learners engaged in concept map completion outperformed those engaged in concept map study on near transfer (p = .010) and far transfer (p < .001) performance. There was a significant interaction effect of learners' prior ability and learning condition on conceptual knowledge but not on near and far transfer performance

Advances in mass spectrometry-based cancer research and analysis: from cancer proteomics to clinical diagnostics.

PubMed

Timms, John F; Hale, Oliver J; Cramer, Rainer

2016-06-01

The last 20 years have seen significant improvements in the analytical capabilities of biological mass spectrometry (MS). Studies using advanced MS have resulted in new insights into cell biology and the etiology of diseases as well as its use in clinical applications. This review discusses recent developments in MS-based technologies and their cancer-related applications with a focus on proteomics. It also discusses the issues around translating the research findings to the clinic and provides an outline of where the field is moving. Expert commentary: Proteomics has been problematic to adapt for the clinical setting. However, MS-based techniques continue to demonstrate potential in novel clinical uses beyond classical cancer proteomics.

How health-related quality of life assessment should be used in advanced colorectal cancer clinical trials.

PubMed

Bonnetain, F; Borg, C; Adams, R R; Ajani, J A; Benson, A; Bleiberg, H; Chibaudel, B; Diaz-Rubio, E; Douillard, J Y; Fuchs, C S; Giantonio, B J; Goldberg, R; Heinemann, V; Koopman, M; Labianca, R; Larsen, A K; Maughan, T; Mitchell, E; Peeters, M; Punt, C J A; Schmoll, H J; Tournigand, C; de Gramont, A

2017-09-01

Traditionally, the efficacy of cancer treatment in patients with advance or metastatic disease in clinical studies has been studied using overall survival and more recently tumor-based end points such as progression-free survival, measurements of response to treatment. However, these seem not to be the relevant clinical end points in current situation if such end points were no validated as surrogate of overall survival to demonstrate the clinical efficacy. Appropriate, meaningful, primary patient-oriented and patient-reported end points that adequately measure the effects of new therapeutic interventions are then crucial for the advancement of clinical research in metastatic colorectal cancer to complement the results of tumor-based end points. Health-related quality of life (HRQoL) is effectively an evaluation of quality of life and its relationship with health over time. HRQoL includes the patient report at least of the way a disease or its treatment affects its physical, emotional and social well-being. Over the past few years, several phase III trials in a variety of solid cancers have assessed the incremental value of HRQoL in addition to the traditional end points of tumor response and survival results. HRQoL could provide not only complementary clinical data to the primary outcomes, but also more precise predictive and prognostic value. This end point is useful for both clinicians and patients in order to achieve the dogma of precision medicine. The present article examines the use of HRQoL in phase III metastatic colorectal cancer clinical trials, outlines the importance of HRQoL assessment methods, analysis, and results presentation. Moreover, it discusses the relevance of including HRQoL as a primary/co-primary end point to support the progression-free survival results and to assess efficacy of treatment in the advanced disease setting. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All

Clinical benefit, price and approval characteristics of FDA-approved new drugs for treating advanced solid cancer, 2000-2015.

PubMed

Vivot, A; Jacot, J; Zeitoun, J-D; Ravaud, P; Crequit, P; Porcher, R

2017-05-01

Prices of anti-cancer drugs are skyrocking. We aimed to assess the clinical benefit of new drugs for treating advanced solid tumors at the time of their approval by the US Food and Drug Administration (FDA) and to search for a relation between price and clinical benefit of drugs. We included all new molecular entities and new biologics for treating advanced solid cancer that were approved by the FDA between 2000 and 2015. The clinical benefit of drugs was graded based on FDA medical review of pivotal clinical trials using the 2016-updated of the American Society of Clinical Oncology Value Framework (ASCO-VF) and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Characteristics of drugs and approvals were obtained from publicly available FDA documents and price was evaluated according to US Medicare, US Veterans Health Administration and United Kingdom market systems. The FDA approved 51 new drugs for advanced solid cancer from 2000 to 2015; we could evaluate the value of 37 drugs (73%). By the ESMO-MCBS, five drugs (14%) were grade one (the lowest), nine (24%) grade two, 10 (27%) grade three, 11 (30%) grade four and two (5%) grade five (the highest). Thus, 13 drugs (35%) showed a meaningful clinical benefit (scale levels 4 and 5). By the ASCO-VF which had a range of 3.4-67, the median drug value was 37 (interquartile range 20-52). We found no relationship between clinical benefit and drug price (P = 0.9). No characteristic of drugs and of approval was significantly associated with clinical benefit. Many recently FDA-approved new cancer drugs did not have high clinical benefit as measured by current scales. We found no relation between the price of drugs and benefit to society and patients. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Evaluating the impact of a pre-rotation workshop on student preparation for clinical advanced pharmacy practice experiences.

PubMed

Medina, Melissa S; Stark, Jennifer E; Vesta, Kimi S; Lockhart, Staci M

2008-10-01

This pilot study was designed to evaluate the impact of a pre-rotation workshop (PRW) on pharmacy students' clinical skills and preparation for clinical Advanced Pharmacy Practice Experiences (APPE) involving direct patient care. Randomized controlled trial of an educational intervention with Institutional Review Board approval. PRW activities designed to simulate rotation activities around five competencies, patient charts, medication histories, SOAP notes, patient presentations, and professionalism. Endpoints were evaluated using clinical rotation preceptors' evaluation of performance and students' performance on objective structured clinical exams (OSCE). Eight fourth-year students and eight GPA matched controls (20% of the total class) were selected to voluntarily participate. The PRW demonstrated a positive impact on students' clinical skills and preparation for rotations by improving OSCE performance. However, no significant differences were found between groups when comparing preceptor evaluations of skills on rotations. These results are limited by the small sample size, potential OSCE "test-wiseness" effects, lack of OSCE evaluator blinding to study groups, potential case specificity effects due to the limited number of cases used on the OSCE and possible lack of sensitivity of the rotation evaluation tool to capture true differences among the experimental and control group participants. The PRW was successful at advancing students' clinical skills and preparation for rotations and may be considered as a tool to help bridge didactic to clinical experiences in the Pharm.D. curriculum.

[Image guided and robotic treatment--the advance of cybernetics in clinical medicine].

PubMed

Fosse, E; Elle, O J; Samset, E; Johansen, M; Røtnes, J S; Tønnessen, T I; Edwin, B

2000-01-10

The introduction of advanced technology in hospitals has changed the treatment practice towards more image guided and minimal invasive procedures. Modern computer and communication technology opens up for robot aided and pre-programmed intervention. Several robotic systems are in clinical use today both in microsurgery and in major cardiac and orthopedic operations. As this trend develops, professions which are new in this context such as physicists, mathematicians and cybernetic engineers will be increasingly important in the treatment of patients.

Clinical response to apatinib monotherapy in advanced non-small cell lung cancer.

PubMed

Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

2018-06-01

Apatinib, an oral tyrosine kinase inhibitor mainly targeting VEGFR-2, exerts both antiangiogenesis and antiproliferation effects. Apatinib shows clinical benefit in advanced non-small cell lung cancer (NSCLC) at an initial dose of 750 mg qd. We further assessed the efficacy and safety of apatinib at a more frequently used dose of 500 mg qd. The preliminary clinical outcome of apatinib in patients with brain metastases was also reported. We retrospectively reviewed the clinical data of 25 patients who received apatinib between August 2015 and May 2016. Progression-free survival (PFS) was calculated by using the Kaplan-Meier method. The objective response rate and disease control rate were 8.0% and 68.0%, respectively. The median PFS was 5.17 (95% confidence interval [CI]: 0.76-9.57) months. In the second-line setting (n = 13), the median PFS was 7.37 (95% CI: 0.01-14.72) months, whereas the median PFS for the 12 patients treated with apatinib as third line or beyond therapy was 5.17 (95% CI: 1.78-8.55) months. Of the seven patients with brain metastases, four patients had stable disease. All patients were well tolerant to apatinib without any grade 3 or 4 adverse events. The most common grade 1 or 2 adverse events included hypertension (72.0%), hand-foot-skin reaction (24.0%), fatigue (24.0%) and abnormal liver function (20.0%). Apatinib is effective and well tolerated in patients with advanced NSCLC, even at a dosage of 500 mg qd, and might offer a new option for the treatment of such patients with brain metastases. © 2017 John Wiley & Sons Australia, Ltd.

Advanced control concepts. [trim solution for space shuttle

NASA Technical Reports Server (NTRS)

Hutton, M. F.; Friedland, B.

1973-01-01

The selection of a trim solution that provides the space shuttle with the highest level of performance and dynamic control in the presense of wind disturbances and bias torques due to misalignment of rocket engines is described. It was determined that engine gimballing is insufficient to provide control to trim the vehicle for headwind and sidewind disturbances, and that it is necessary to use aerodynamic surfaces in conjunction with engine gimballing to achieve trim. The algebraic equations for computing the trim solution were derived from the differential equations describing the motion of the vehicle by substituting the desired trim conditions. The general problem of showing how the trim equations are derived from the equations of motion and the mathematical forms of the performance criterion is discussed in detail, along with the general equations for studying the dynamic response of the trim solution.

Clinical Perspectives on Lupus Genetics: Advances and Opportunities

PubMed Central

James, Judith A.

2014-01-01

Synopsis In recent years, genome wide association studies have led to an explosion in the identification of regions containing confirmed genetic risk variants within complex human diseases, for example in systemic lupus erythematosus (SLE). Many of these strongest SLE genetic associations can be divided into groups based upon their potential roles in different processes implicated in lupus pathogenesis, including ubiquitination (a process of marking proteins for degradation), DNA degradation, innate immunity, cellular immunity (B cell, T cell, neutrophil, monocytes), lymphocyte development, and antigen presentation. Recent advances have also demonstrated several genetic associations with SLE subphenotypes and subcriteria, such as autoantibody production, lupus nephritis, serositis, and arthritis. Despite the broad range of lupus genetic studies to date, many areas for further exploration remain to move lupus genetic studies toward clinically informative endpoints, such as identifying individuals at the greatest risk of end-organ damage, early mortality or poor response to a specific therapeutic regimen. PMID:25034154

Advances in asthma, allergy and immunology series 2004: basic and clinical immunology.

PubMed

Chinen, Javier; Shearer, William T

2004-08-01

This review highlights some of the most significant advances in basic and clinical immunology that were published from August 2002 to December 2003, focusing on manuscripts that appeared in the Journal. Articles selected were those considered most relevant to Journal readers. With regard to basic immunology, this report includes articles describing FcepsilonRI expression in mucosal Langerhans cells and type II dendritic cells, mechanisms of TH1 and TH2 regulation, the role of Foxp3 in the development of CD4+CD25+ regulatory T cells, and the increasing importance of Toll receptors in immunity. Articles related to clinical immunology that were selected include the first report of lymphocyte subsets values from a large cohort of normal children; the description of new genetic defects in primary immunodeficiencies; a description of the complications of gene therapy for X-linked severe combined immunodeficiency; a report of 79 patients with hyper-IgM syndrome; a report of the mechanism of action and complications of intravenous immunoglobulin; a report of new approaches for immunotherapy; and an article on advances in HIV infection and management, including a report of defensins, small molecules with anti-HIV properties. Also summarized is an article that studied the immune system during a prolonged stay in the Antarctic, a model for human studies on the effect of environmental conditions similar to space expeditions.

New clinical advances in immunotherapy for the treatment of solid tumours

PubMed Central

Zavala, Valentina A; Kalergis, Alexis M

2015-01-01

Advances in understanding the mechanisms of cancer cells for evading the immune system surveillance, including how the immune system modulates the phenotype of tumours, have allowed the development of new therapies that benefit from this complex cellular network to specifically target and destroy cancer cells. Immunotherapy researchers have mainly focused on the discovery of tumour antigens that could confer specificity to immune cells to detect and destroy cancer cells, as well as on the mechanisms leading to an improved activation of effector immune cells. The Food and Drug Administration approval in 2010 of ipilumumab for melanoma treatment and of pembrolizumab in 2014, monoclonal antibodies against T-lymphocyte-associated antigen 4 and programmed cell death 1, respectively, are encouraging examples of how research in this area can successfully translate into clinical use with promising results. Currently, several ongoing clinical trials are in progress testing new anti-cancer therapies based on the enhancement of immune cell activity against tumour antigens. Here we discuss the general concepts related to immunotherapy and the recent application to the treatment of cancer with positive results that support their consideration of clinical application to patients. PMID:25826229

Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: part III - convergence toward clinical trials.

PubMed

Bested, Alison C; Logan, Alan C; Selhub, Eva M

2013-03-16

Rapid scientific and technological advances have allowed for a more detailed understanding of the relevance of intestinal microbiota, and the entire body-wide microbiome, to human health and well-being. Rodent studies have provided suggestive evidence that probiotics (e.g. lactobacillus and bifidobacteria) can influence behavior. More importantly, emerging clinical studies indicate that the administration of beneficial microbes, via supplementation and/or fecal microbial transplant (FMT), can influence end-points related to mood state (glycemic control, oxidative status, uremic toxins), brain function (functional magnetic resonance imaging fMRI), and mental outlook (depression, anxiety). However, despite the advances in the area of gastro-biological psychiatry, it becomes clear that there remains an urgent need to explore the value of beneficial microbes in controlled clinical investigations. With the history explored in this series, it is fair to ask if we are now on the cusp of major clinical breakthroughs, or are we merely in the quicksand of Autointoxication II?

Microplates in liquid chromatography--new solution in clinical research? A review.

PubMed

Krcmova, Lenka; Solichova, Dagmar; Solich, Petr

2013-10-15

Microplates are routinely used in Radio- or Immuno-assays. Recently, microplates have found use not only in analytical but also in the pre-analytical phase in bioanalyses (sample storage, sample preparation). New connection of this technology to liquid chromatography could be economical, fast and simple solution for many routine laboratories handling large sequences of biological samples. This review summarises the application of microplates in bioanalytical laboratories. Different types of sorbents, materials and shapes of microplates are discussed, and the main advantages and disadvantages of microplates used in clinical research are presented. Copyright © 2013 Elsevier B.V. All rights reserved.

Extended cooperation in clinical studies through exchange of CDISC metadata between different study software solutions.

PubMed

Kuchinke, W; Wiegelmann, S; Verplancke, P; Ohmann, C

2006-01-01

Our objectives were to analyze the possibility of an exchange of an entire clinical study between two different and independent study software solutions. The question addressed was whether a software-independent transfer of study metadata can be performed without programming efforts and with software routinely used for clinical research. Study metadata was transferred with ODM standard (CDISC). Study software systems employed were MACRO (InferMed) and XTrial (XClinical). For the Proof of Concept, a test study was created with MACRO and exported as ODM. For modification and validation of the ODM export file XML-Spy (Altova) and ODM-Checker (XML4Pharma) were used. Through exchange of a complete clinical study between two different study software solutions, a Proof of Concept of the technical feasibility of a system-independent metadata exchange was conducted successfully. The interchange of study metadata between two different systems at different centers was performed with minimal expenditure. A small number of mistakes had to be corrected in order to generate a syntactically correct ODM file and a "vendor extension" had to be inserted. After these modifications, XTrial exhibited the study, including all data fields, correctly. However, the optical appearance of both CRFs (case report forms) was different. ODM can be used as an exchange format for clinical studies between different study software. Thus, new forms of cooperation through exchange of metadata seem possible, for example the joint creation of electronic study protocols or CRFs at different research centers. Although the ODM standard represents a clinical study completely, it contains no information about the representation of data fields in CRFs.

Improved resident physician confidence with advance care planning after an ambulatory clinic intervention.

PubMed

Tung, Ericka E; Wieland, Mark L; Verdoorn, Brandon P; Mauck, Karen F; Post, Jason A; Thomas, Matthew R; Bundrick, John B; Jaeger, Thomas M; Cha, Stephen S; Thomas, Kris G

2014-05-01

Many primary care providers feel uncomfortable discussing end-of-life care. The aim of this intervention was to assess internal medicine residents' advance care planning (ACP) practices and improve residents' ACP confidence. Residents participated in a facilitated ACP quality improvement workshop, which included an interactive presentation and chart audit of their own patients. Pre- and postintervention surveys assessed resident ACP-related confidence. Only 24% of the audited patients had an advance directive (AD), and 28% of the ACP-documentation was of no clinical utility. Terminally ill patients (odds ratio 2.8, P < .001) were more likely to have an AD. Patients requiring an interpreter were less likely to have participated in ACP. Residents reported significantly improved confidence with ACP and identified important training gaps. Future studies examining the impact on ACP quality are needed.

WE-DE-207A-00: Advances in Image-Guided Neurointerventions-Clinical Pull and Technology Push

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

NONE

for the audience. Learning Objectives: To understand the clinical need of one-stop-shop stroke imaging workflow To understand to technical challenges in cone beam CT perfusion To understand the potential technical solutions to enable one-stop-shop imaging workflow Recent advances in devices used in neuro--interventions Mattew Gounis - Over the past two decades, there has been explosive development of medical devices that have revolutionized the endovascular treatment of cerebrovascular diseases. There is now Level 1, Class A evidence that intra-arterial, mechanical thrombectomy in acute ischemic stroke is superior to medical management; and similarly that minimally invasive, endovascular repair of ruptured brain aneurysms is superior to surgical treatment. Stent-retrievers are now standard of care for emergent large vessel occlusions causing a stroke, with a number of patients need to treat for good clinical outcomes as low as 4. Recent technologies such as flow diverters and disrupters, intracranial self-expanding stents, flexible large bore catheters that can reach vessels beyond the circle of Willis, stent-retrievers, and super-compliant balloons are the result of successful miniaturization of design features and novel manufacturing technologies capable of building these devices. This is a rapidly evolving field, and the device technology enabling such advancements will be reviewed. Importantly, image-guidance technology has not kept pace in neurointervention and the ability to adequately characterize these devices in vivo remains a significant opportunity. Learning Objectives: A survey of devices used in neurointerventions, their materials and essential design characteristics Funding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; G. Chen, Funding received from NIH; funding received from DOD; funding received from GE Healthcare; funding received

A Systematic Review of Wearable Patient Monitoring Systems - Current Challenges and Opportunities for Clinical Adoption.

PubMed

Baig, Mirza Mansoor; GholamHosseini, Hamid; Moqeem, Aasia A; Mirza, Farhaan; Lindén, Maria

2017-07-01

The aim of this review is to investigate barriers and challenges of wearable patient monitoring (WPM) solutions adopted by clinicians in acute, as well as in community, care settings. Currently, healthcare providers are coping with ever-growing healthcare challenges including an ageing population, chronic diseases, the cost of hospitalization, and the risk of medical errors. WPM systems are a potential solution for addressing some of these challenges by enabling advanced sensors, wearable technology, and secure and effective communication platforms between the clinicians and patients. A total of 791 articles were screened and 20 were selected for this review. The most common publication venue was conference proceedings (13, 54%). This review only considered recent studies published between 2015 and 2017. The identified studies involved chronic conditions (6, 30%), rehabilitation (7, 35%), cardiovascular diseases (4, 20%), falls (2, 10%) and mental health (1, 5%). Most studies focussed on the system aspects of WPM solutions including advanced sensors, wireless data collection, communication platform and clinical usability based on a specific area or disease. The current studies are progressing with localized sensor-software integration to solve a specific use-case/health area using non-scalable and 'silo' solutions. There is further work required regarding interoperability and clinical acceptance challenges. The advancement of wearable technology and possibilities of using machine learning and artificial intelligence in healthcare is a concept that has been investigated by many studies. We believe future patient monitoring and medical treatments will build upon efficient and affordable solutions of wearable technology.

Parental consanguineous marriages and clinical response to chemotherapy in locally advanced breast cancer patients.

PubMed

Saadat, Mostafa; Khalili, Maryam; Omidvari, Shahpour; Ansari-Lari, Maryam

2011-03-28

The main aim of the present study was investigating the association between parental consanguinity and clinical response to chemotherapy in females affected with locally advanced breast cancer. A consecutive series of 92 patients were prospectively included in this study. Clinical assessment of treatment was accomplished by comparing initial tumor size with preoperative tumor size using revised RECIST guideline (version 1.1). Clinical response defined as complete response, partial response and no response. The Kaplan-Meier survival analysis were used to evaluate the association of parental marriages (first cousin vs unrelated marriages) and clinical response to chemotherapy (complete and partial response vs no response). Number of courses of chemotherapy was considered as time, in the analysis. Kaplan-Meier analysis revealed that offspring of unrelated marriages had poorer response to chemotherapy (log rank statistic=5.10, df=1, P=0.023). Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

[Implementation of bedside training and advanced objective structured clinical examination (OSCE) trial to learn and confirm about pharmacy clinical skills].

PubMed

Tokunaga, Jin; Takamura, Norito; Ogata, Kenji; Setoguchi, Nao; Sato, Keizo

2013-01-01

Bedside training for fourth-year students, as well as seminars in hospital pharmacy (vital sign seminars) for fifth-year students at the Department of Pharmacy of Kyushu University of Health and Welfare have been implemented using patient training models and various patient simulators. The introduction of simulation-based pharmaceutical education, where no patients are present, promotes visually, aurally, and tactilely simulated learning regarding the evaluation of vital signs and implementation of physical assessment when disease symptoms are present or adverse effects occur. A patient simulator also promotes the creation of training programs for emergency and critical care, with which basic as well as advanced life support can be practiced. In addition, an advanced objective structured clinical examination (OSCE) trial has been implemented to evaluate skills regarding vital signs and physical assessments. Pharmacists are required to examine vital signs and conduct physical assessment from a pharmaceutical point of view. The introduction of these pharmacy clinical skills will improve the efficacy of drugs, work for the prevention or early detection of adverse effects, and promote the appropriate use of drugs. It is considered that simulation-based pharmaceutical education is essential to understand physical assessment, and such education will ideally be applied and developed according to on-site practices.

Advances in Neuroprosthetic Learning and Control

PubMed Central

Carmena, Jose M.

2013-01-01

Significant progress has occurred in the field of brain–machine interfaces (BMI) since the first demonstrations with rodents, monkeys, and humans controlling different prosthetic devices directly with neural activity. This technology holds great potential to aid large numbers of people with neurological disorders. However, despite this initial enthusiasm and the plethora of available robotic technologies, existing neural interfaces cannot as yet master the control of prosthetic, paralyzed, or otherwise disabled limbs. Here I briefly discuss recent advances from our laboratory into the neural basis of BMIs that should lead to better prosthetic control and clinically viable solutions, as well as new insights into the neurobiology of action. PMID:23700383

Advances in neuroprosthetic learning and control.

PubMed

Carmena, Jose M

2013-01-01

Significant progress has occurred in the field of brain-machine interfaces (BMI) since the first demonstrations with rodents, monkeys, and humans controlling different prosthetic devices directly with neural activity. This technology holds great potential to aid large numbers of people with neurological disorders. However, despite this initial enthusiasm and the plethora of available robotic technologies, existing neural interfaces cannot as yet master the control of prosthetic, paralyzed, or otherwise disabled limbs. Here I briefly discuss recent advances from our laboratory into the neural basis of BMIs that should lead to better prosthetic control and clinically viable solutions, as well as new insights into the neurobiology of action.

Studying physician-adolescent patient communication in community-based practices: recruitment challenges and solutions.

PubMed

Bodner, Michael E; Bilheimer, Alicia; Gao, Xiaomei; Lyna, Pauline; Alexander, Stewart C; Dolor, Rowena J; Østbye, Truls; Bravender, Terrill; Tulsky, James A; Graves, Sidney; Irons, Alexis; Pollak, Kathryn I

2015-11-13

Practice-based studies are needed to assess how physicians communicate health messages about weight to overweight/obese adolescent patients, but successful recruitment to such studies is challenging. This paper describes challenges, solutions, and lessons learned to recruit physicians and adolescents to the Teen Communicating Health Analyzing Talk (CHAT) study, a randomized controlled trial of a communication skills intervention for primary care physicians to enhance communication about weight with overweight/obese adolescents. A "peer-to-peer" approach was used to recruit physicians, including the use of "clinic champions" who liaised between study leaders and physicians. Consistent rapport and cooperative working relationships with physicians and clinic staff were developed and maintained. Adolescent clinic files were reviewed (HIPAA waiver) to assess eligibility. Parents could elect to opt-out for their children. To encourage enrollment, confidentiality of audio recordings was emphasized, and financial incentives were offered to all participants. We recruited 49 physicians and audio-recorded 391 of their overweight/obese adolescents' visits. Recruitment challenges included 1) physician reticence to participate; 2) variability in clinic operating procedures; 3) variability in adolescent accrual rates; 4) clinic open access scheduling; and 5) establishing communication with parents and adolescents. Key solutions included the use of a "clinic champion" to help recruit physicians, pro-active, consistent communication with clinic staff, and adapting calling times to reach parents and adolescents. Recruiting physicians and adolescents to audio-recorded, practice-based health communication studies can be successful. Anticipated challenges to recruiting can be met with advanced planning; however, optimal solutions to challenges evolve as recruitment progresses.

Advanced in Visualization of 3D Time-Dependent CFD Solutions

NASA Technical Reports Server (NTRS)

Lane, David A.; Lasinski, T. A. (Technical Monitor)

1995-01-01

Numerical simulations of complex 3D time-dependent (unsteady) flows are becoming increasingly feasible because of the progress in computing systems. Unfortunately, many existing flow visualization systems were developed for time-independent (steady) solutions and do not adequately depict solutions from unsteady flow simulations. Furthermore, most systems only handle one time step of the solutions individually and do not consider the time-dependent nature of the solutions. For example, instantaneous streamlines are computed by tracking the particles using one time step of the solution. However, for streaklines and timelines, particles need to be tracked through all time steps. Streaklines can reveal quite different information about the flow than those revealed by instantaneous streamlines. Comparisons of instantaneous streamlines with dynamic streaklines are shown. For a complex 3D flow simulation, it is common to generate a grid system with several millions of grid points and to have tens of thousands of time steps. The disk requirement for storing the flow data can easily be tens of gigabytes. Visualizing solutions of this magnitude is a challenging problem with today's computer hardware technology. Even interactive visualization of one time step of the flow data can be a problem for some existing flow visualization systems because of the size of the grid. Current approaches for visualizing complex 3D time-dependent CFD solutions are described. The flow visualization system developed at NASA Ames Research Center to compute time-dependent particle traces from unsteady CFD solutions is described. The system computes particle traces (streaklines) by integrating through the time steps. This system has been used by several NASA scientists to visualize their CFD time-dependent solutions. The flow visualization capabilities of this system are described, and visualization results are shown.

Multi-analyte validation in heterogeneous solution by ELISA.

PubMed

Lakshmipriya, Thangavel; Gopinath, Subash C B; Hashim, Uda; Murugaiyah, Vikneswaran

2017-12-01

Enzyme Linked Immunosorbent Assay (ELISA) is a standard assay that has been used widely to validate the presence of analyte in the solution. With the advancement of ELISA, different strategies have shown and became a suitable immunoassay for a wide range of analytes. Herein, we attempted to provide additional evidence with ELISA, to show its suitability for multi-analyte detection. To demonstrate, three clinically relevant targets have been chosen, which include 16kDa protein from Mycobacterium tuberculosis, human blood clotting Factor IXa and a tumour marker Squamous Cell Carcinoma antigen. Indeed, we adapted the routine steps from the conventional ELISA to validate the occurrence of analytes both in homogeneous and heterogeneous solutions. With the homogeneous and heterogeneous solutions, we could attain the sensitivity of 2, 8 and 1nM for the targets 16kDa protein, FIXa and SSC antigen, respectively. Further, the specific multi-analyte validations were evidenced with the similar sensitivities in the presence of human serum. ELISA assay in this study has proven its applicability for the genuine multiple target validation in the heterogeneous solution, can be followed for other target validations. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative study of the thermal properties of mud and peat solutions applied in clinical practice.

PubMed

Beer, A M; Grozeva, A; Sagorchev, P; Lukanov, J

2003-11-01

Different peloids as e.g. mud and peat have been traditionally used for therapeutic purposes successfully, especially of there thermal actions. It was the aim of the experimental study to compare the thermal properties of two peloids, mud and peat, with a view to assessing their thermal effects when they are applied in clinical practice. The studies were carried out using peat of the marsh type of peats (Hochmoor), and curative Pomorie (Bulgaria) mud. As important parameters were determined the specific thermal capacity at constant pressure (Cp), the density of solutions (rho), the cooling rate (m), the coefficient of temperature transfer (a) of solutions and the coefficient of thermal conductivity (lambda) of solutions of peat and curative mud, compared to water bath. The comparative studies of the thermal properties of water and water solutions of peat and curative mud show that the thermal effect of the water bath is substantially smaller than that of the peat and mud applications. This difference is due to a greater extent to the high values of the dynamic viscosity, not allowing cooling by convection and protecting the surface of the skin upon applications of peloid solutions with a higher temperature.

Advancing clinical reasoning in virtual patients - development and application of a conceptual framework.

PubMed

Hege, Inga; Kononowicz, Andrzej A; Berman, Norman B; Lenzer, Benedikt; Kiesewetter, Jan

2018-01-01

Background: Clinical reasoning is a complex skill students have to acquire during their education. For educators it is difficult to explain their reasoning to students, because it is partly an automatic and unconscious process. Virtual Patients (VPs) are used to support the acquisition of clinical reasoning skills in healthcare education. However, until now it remains unclear which features or settings of VPs optimally foster clinical reasoning. Therefore, our aims were to identify key concepts of the clinical reasoning process in a qualitative approach and draw conclusions on how each concept can be enhanced to advance the learning of clinical reasoning with virtual patients. Methods: We chose a grounded theory approach to identify key categories and concepts of learning clinical reasoning and develop a framework. Throughout this process, the emerging codes were discussed with a panel of interdisciplinary experts. In a second step we applied the framework to virtual patients. Results: Based on the data we identified the core category as the "multifactorial nature of learning clinical reasoning". This category is reflected in the following five main categories: Psychological Theories, Patient-centeredness, Context, Learner-centeredness, and Teaching/Assessment. Each category encompasses between four and six related concepts. Conclusions: With our approach we were able to elaborate how key categories and concepts of clinical reasoning can be applied to virtual patients. This includes aspects such as allowing learners to access a large number of VPs with adaptable levels of complexity and feedback or emphasizing dual processing, errors, and uncertainty.

Advances in endodontics: Potential applications in clinical practice

PubMed Central

Kishen, Anil; Peters, Ove A.; Zehnder, Matthias; Diogenes, Anibal R.; Nair, Madhu K.

2016-01-01

Contemporary endodontics has seen an unprecedented advance in technology and materials. This article aimed to review some of the challenges and advances in the following sections: (1) endodontic imaging, (2) root canal preparation, (3) root canal disinfection, (4) root canal filling, and (4) regenerative endodontic procedures (REPs). Jointly, these advances are aimed at improving the state of the art and science of root canal treatment. PMID:27217630

Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application

PubMed Central

Li, Kaichun; Li, Jin

2016-01-01

Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2), can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab), VEGF targeting monoclonal antibodies (bevacizumab), mTOR inhibitor (everolimus), or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer. PMID:26880889

Clinical Model for NASH and Advanced Fibrosis in Adult Patients With Diabetes and NAFLD: Guidelines for Referral in NAFLD

PubMed Central

Bazick, Jessica; Donithan, Michele; Neuschwander-Tetri, Brent A.; Kleiner, David; Brunt, Elizabeth M.; Wilson, Laura; Doo, Ed; Lavine, Joel; Tonascia, James

2015-01-01

OBJECTIVE Approximately 18 million people in the U.S. have coexisting type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). It is not known who among these patients has nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Therefore, we aimed to determine factors that are associated with both NASH and advanced fibrosis in patients with diabetes and NAFLD in order to identify who should be prioritized for referral to a hepatologist for further diagnostic evaluation and treatment. RESEARCH DESIGN AND METHODS This study was derived from the NASH Clinical Research Network studies and included 1,249 patients with biopsy-proven NAFLD (including a model development cohort of 346 patients and an independent validation cohort of 100 patients with type 2 diabetes as defined by the American Diabetes Association criteria). Outcome measures were presence of NASH or advanced fibrosis (stage 3 or 4) using cross-validated, by jackknife method, multivariable-adjusted area under the receiver operating characteristic curve (AUROC) and 95% CI. RESULTS The mean ± SD age and BMI of patients with diabetes and NAFLD was 52.5 ± 10.3 years and 35.8 ± 6.8 kg/m2, respectively. The prevalence of NASH and advanced fibrosis was 69.2% and 41.0%, respectively. The model for NASH included white race, BMI, waist, alanine aminotransferase (ALT), Aspartate aminotransferase (AST), albumin, HbA1c, HOMA of insulin resistance, and ferritin with an AUROC of 0.80 (95% CI 0.75–0.84, P = 0.007). The specificity, sensitivity, negative predictive values (NPVs), and positive predictive values (PPVs) were 90.0%, 56.8%, 47.7%, and 93.2%, respectively, and the model correctly classified 67% of patients as having NASH. The model for predicting advanced fibrosis included age, Hispanic ethnicity, BMI, waist-to-hip ratio, hypertension, ALT-to-AST ratio, alkaline phosphatase, isolated abnormal alkaline phosphatase, bilirubin (total and direct), globulin, albumin, serum insulin, hematocrit

Clinical and histological determinants of nonalcoholic steatohepatitis and advanced fibrosis in elderly patients.

PubMed

Noureddin, Mazen; Yates, Katherine P; Vaughn, Ivana A; Neuschwander-Tetri, Brent A; Sanyal, Arun J; McCullough, Arthur; Merriman, Raphael; Hameed, Bilal; Doo, Edward; Kleiner, David E; Behling, Cynthia; Loomba, Rohit

2013-11-01

The characteristics of nonalcoholic fatty liver disease (NAFLD) in elderly patients are unknown. Therefore, we aimed to examine the differences between elderly and nonelderly patients with NAFLD and to identify determinants of nonalcoholic steatohepatitis (NASH) and advanced fibrosis (bridging fibrosis or cirrhosis) in elderly patients. This is a cross-sectional analysis of adult participants who were prospectively enrolled in the NASH Clinical Research Network studies. Participants were included based on availability of the centrally reviewed liver histology data within 1 year of enrollment, resulting in 61 elderly (age ≥65 years) and 735 nonelderly (18-64 years) participants. The main outcomes were the presence of NASH and advanced fibrosis. Compared to nonelderly patients with NAFLD, elderly patients had a higher prevalence of NASH (56% versus 72%, P = 0.02), and advanced fibrosis (25% versus 44%, P = 0.002). Compared to nonelderly patients with NASH, elderly patients with NASH had higher rates of advanced fibrosis (35% versus 52%, P = 0.03), as well as other features of severe liver disease including the presence of ballooning degeneration, acidophil bodies, megamitochondria, and Mallory-Denk bodies (P ≤ 0.05 for each). In multiple logistic regression analyses, independent determinants of NASH in elderly patients included higher aspartate aminotransferase (AST) (odds ratio [OR] = 1.12, P = 0.007) and lower platelets (OR = 0.98, P = 0.02); and independent determinants of advanced fibrosis included higher AST (OR = 1.08, P = 0.007), lower alanine aminotransferase value (OR = 0.91, P = 0.002), and an increased odds of having low high-density lipoprotein (OR = 8.35, P = 0.02). Elderly patients are more likely to have NASH and advanced fibrosis than nonelderly patients with NAFLD. Liver biopsy may be considered in elderly patients and treatment should be initiated in those with NASH and advanced fibrosis. �

A simple versatile solution for collecting multidimensional clinical data based on the CakePHP web application framework.

PubMed

Biermann, Martin

2014-04-01

Clinical trials aiming for regulatory approval of a therapeutic agent must be conducted according to Good Clinical Practice (GCP). Clinical Data Management Systems (CDMS) are specialized software solutions geared toward GCP-trials. They are however less suited for data management in small non-GCP research projects. For use in researcher-initiated non-GCP studies, we developed a client-server database application based on the public domain CakePHP framework. The underlying MySQL database uses a simple data model based on only five data tables. The graphical user interface can be run in any web browser inside the hospital network. Data are validated upon entry. Data contained in external database systems can be imported interactively. Data are automatically anonymized on import, and the key lists identifying the subjects being logged to a restricted part of the database. Data analysis is performed by separate statistics and analysis software connecting to the database via a generic Open Database Connectivity (ODBC) interface. Since its first pilot implementation in 2011, the solution has been applied to seven different clinical research projects covering different clinical problems in different organ systems such as cancer of the thyroid and the prostate glands. This paper shows how the adoption of a generic web application framework is a feasible, flexible, low-cost, and user-friendly way of managing multidimensional research data in researcher-initiated non-GCP clinical projects. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

PubMed

Margulies, Kenneth B; Hernandez, Adrian F; Redfield, Margaret M; Givertz, Michael M; Oliveira, Guilherme H; Cole, Robert; Mann, Douglas L; Whellan, David J; Kiernan, Michael S; Felker, G Michael; McNulty, Steven E; Anstrom, Kevin J; Shah, Monica R; Braunwald, Eugene; Cappola, Thomas P

2016-08-02

Abnormal cardiac metabolism contributes to the pathophysiology of advanced heart failure with reduced left ventricular ejection fraction (LVEF). Glucagon-like peptide 1 (GLP-1) agonists have shown cardioprotective effects in early clinical studies of patients with advanced heart failure, irrespective of type 2 diabetes status. To test whether therapy with a GLP-1 agonist improves clinical stability following hospitalization for acute heart failure. Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with established heart failure and reduced LVEF who were recently hospitalized. Patients were enrolled between August 2013 and March 2015 at 24 US sites. The GLP-1 agonist liraglutide (n = 154) or placebo (n = 146) via a daily subcutaneous injection; study drug was advanced to a dosage of 1.8 mg/d during the first 30 days as tolerated and continued for 180 days. The primary end point was a global rank score in which all patients, regardless of treatment assignment, were ranked across 3 hierarchical tiers: time to death, time to rehospitalization for heart failure, and time-averaged proportional change in N-terminal pro-B-type natriuretic peptide level from baseline to 180 days. Higher values indicate better health (stability). Exploratory secondary outcomes included primary end point components, cardiac structure and function, 6-minute walk distance, quality of life, and combined events. Among the 300 patients who were randomized (median age, 61 years [interquartile range {IQR}, 52-68 years]; 64 [21%] women; 178 [59%] with type 2 diabetes; median LVEF of 25% [IQR, 19%-33%]; median N-terminal pro-B-type natriuretic peptide level of 2049 pg/mL [IQR, 1054-4235 pg/mL]), 271 completed the study. Compared with placebo, liraglutide had no significant effect on the primary end point (mean rank of 146 for the liraglutide group vs 156 for the placebo group, P = .31). There were no significant between-group differences in the number of

How novice, skilled and advanced clinical researchers include variables in a case report form for clinical research: a qualitative study

PubMed Central

Chu, Hongling; Zeng, Lin; Fetters, Micheal D; Li, Nan; Tao, Liyuan; Shi, Yanyan; Zhang, Hua; Wang, Xiaoxiao; Li, Fengwei; Zhao, Yiming

2017-01-01

Objectives Despite varying degrees in research training, most academic clinicians are expected to conduct clinical research. The objective of this research was to understand how clinical researchers of different skill levels include variables in a case report form for their clinical research. Setting The setting for this research was a major academic institution in Beijing, China. Participants The target population was clinical researchers with three levels of experience, namely, limited clinical research experience, clinicians with rich clinical research experience and clinical research experts. Methods Using a qualitative approach, we conducted 13 individual interviews (face to face) and one group interview (n=4) with clinical researchers from June to September 2016. Based on maximum variation sampling to identify researchers with three levels of research experience: eight clinicians with limited clinical research experience, five clinicians with rich clinical research experience and four clinical research experts. These 17 researchers had diverse hospital-based medical specialties and or specialisation in clinical research. Results Our analysis yields a typology of three processes developing a case report form that varies according to research experience level. Novice clinician researchers often have an incomplete protocol or none at all, and conduct data collection and publication based on a general framework. Experienced clinician researchers include variables in the case report form based on previous experience with attention to including domains or items at risk for omission and by eliminating unnecessary variables. Expert researchers consider comprehensively in advance data collection and implementation needs and plan accordingly. Conclusion These results illustrate increasing levels of sophistication in research planning that increase sophistication in selection for variables in the case report form. These findings suggest that novice and intermediate

Clinical Improvement of Subacute and Chronic Otitis Media With Effusion Treated With Hyaluronic Acid Plus Hypertonic Solution via Nasal Lavage: A Randomized Controlled Trial.

PubMed

Cioffi, Luigi; Gallo, Patrizia; D'Avino, Antonio; Carlomagno, Francesco; Aloi, Giuseppe; D'Onofrio, Antonietta; Del Gaizo, Donatella; Giuliano, Maria; De Franchis, Raffaella; Sandomenico, Maria L; Pecoraro, Anna

2017-01-01

Background . This study, a randomized controlled trial, aims to demonstrate a clinically significant improvement in subacute and chronic otitis media with effusion through the administration of hyaluronic acid associated with hypertonic solution compared with the administration of hypertonic solution alone. The setting was an outpatient clinic of 20 primary care pediatrician offices affiliated with the 3 Local Health Units (Azienda Sanitaria Locale) of Naples. Materials and Methods . The study was conducted for 6 months, from October 2014 to the end of March 2015. The study saw the participation of 20 pediatricians who were experts in pneumatic otoscopy, each of whom enrolled 15 children. Each investigator was randomized to carry out the treatment with 3% hypertonic solution or high-molecular-weight hyaluronic acid + 3% hypertonic solution. Results . A total of 275 children were enrolled, of whom 11(equal to 4% ) were lost to follow-up. A total of 264 children completed the trial according to the protocol, 120 in the hyaluronic acid + hypertonic solution group and 144 in the hypertonic solution group. Hyaluronic acid associated with hypertonic solution and hypertonic solution alone administered by nasal lavage have proven to be safe and effective in the treatment of prolonged otitis media with effusion (initial score of -0.5, final score of 0.9, P < 001, for the hypertonic + hyaluronic acid group; initial score of -0.3, final score of 0.2, P < .001, for the hypertonic solution group). Though starting from a less favorable initial clinical score (-0.5 vs -0.3, P < .016), hyaluronic acid associated with hypertonic solution resulted in a significant increase in clinical healing (0.9 vs 0.2, P < .001). One interesting outcome was the significant reduction in the consumption of drugs (cortisone and antibiotics) during the follow-up.

Concordance of clinical diagnosis of T classification among physicians for locally advanced unresectable thoracic esophageal cancer.

PubMed

Yokota, Tomoya; Yasuda, Takushi; Kato, Hiroyuki; Nozaki, Isao; Sato, Hiroshi; Miyata, Yoshinori; Kuroki, Yoshifumi; Kato, Ken; Hamamoto, Yasuo; Tsubosa, Yasuhiro; Ogawa, Hirofumi; Ito, Yoshinori; Kitagawa, Yuko

2018-02-01

We conducted a multicenter phase II trial assessing chemoselection with docetaxel plus 5-fluorouracil and cisplatin induction chemotherapy and subsequent conversion surgery for locally advanced, unresectable esophageal cancer. The aim of this study was to validate the concordance of clinical T diagnosis among physicians in the cases of this trial. Computed tomography scans and esophagoscopic images of 48 patients taken at baseline were centrally reviewed by 6 senior physicians with experience in esophageal oncology. Individual reviewers voted for definitive T4, relative T4, relative T3, or definitive T3. Discordant diagnoses between reviewers were resolved by the majority opinion. The reviewers were blinded to patient clinical outcome data and to the vote of the other reviewers. Ninety percent of cases were diagnosed as clinical T4 by investigators, while 33.3-75.0% (median 70.8%) of cases were judged to be T4 by 6 reviewers. Discordant diagnosis between investigators and reviewers occurred in 33% (16/48) of all cases (Cohen's kappa coefficient 0.0519), including 12 cases where curative resection was considered possible (48%, n = 25) and 4 cases where curative resection was considered impossible (17%, n = 23). Critical discordance (one reviewer voted for definitive T3 but the other voted for definitive T4, and vice versa) between reviewers occurred in 0-12.5% of cases (median 2.1%). There were inter-observer variations in clinical diagnosis of the T category of locally advanced, unresectable esophageal cancer. Accurate clinical diagnosis of T classification is required for determining the optimum treatment for each patient.

Implementation of an advanced clinical and administrative hospital information system.

PubMed

Vegoda, P R; Dyro, J F

1986-01-01

Over the last six years since University Hospital opened, the University Hospital Information System (UHIS) has continued to evolve to what is today an advanced administrative and clinical information system. At University Hospital UHIS is the way of conducting business. A wide range of patient care applications are operational including Patient Registration, ADT for Inpatient/Outpatient/Emergency Room visits, Advanced Order Entry/Result Reporting, Medical Records, Lab Automated Data Acquisition/Quality Control, Pharmacy, Radiology, Dietary, Respiratory Therapy, ECG, EEG, Cardiology, Physical/Occupational Therapy and Nursing. These systems and numerous financial systems have been installed in a highly tuned, efficient computer system. All applications are real-time, on-line, and data base oriented. Each system is provided with multiple data security levels, forward file recovery, and dynamic transaction backout of in-flight tasks. Sensitive medical information is safeguarded by job function passwords, identification codes, need-to-know master screens and terminal keylocks. University Hospital has an IBM 3083 CPU with five 3380 disk drives, four dual density tape drives, and a 3705 network controller. The network of 300 terminals and 100 printers is connected to the computer center by an RF broadband cable. The software is configured around the IBM/MVS operating system using CICS as the telecommunication monitor, IMS as the data base management system and PCS/ADS as the application enabling tool. The most extensive clinical system added to UHIS is the Physiological Monitoring/Patient Data Management System with serves 92 critical care beds. In keeping with the Hospital's philosophy of integrated computing, the PMS/PDMS with its network of minicomputers was linked to the UHIS system. In a pilot program, remote access to UHIS through the IBM personal computer has been implemented in several physician offices in the local community, further extending the communications

How institutional change and individual researchers helped advance clinical guidelines in American health care.

PubMed

Nigam, Amit

2013-06-01

Clinical guidelines are important tools for managing health care quality. Research on the origins of guidelines primarily focuses on the institutional causes of their emergence and growth. Individual medical researchers, however, have played important roles. This paper develops knowledge of the role of individual medical researchers in advancing guidelines, and of how researchers' efforts were enabled or constrained by broader institutional changes. Drawing on an analytical case study focused on the role of Kerr White, John Wennberg, and Robert Brook, it shows that guidelines were a product of the interplay between institutional change in the medical field and actions by individual researchers, acting as institutional entrepreneurs. Increased government involvement in the health care field triggered the involvement of a range of new actors in health care. These new organizations created a context that allowed individual researchers to advance guidelines by creating job opportunities, providing research funding, and creating opportunities for researchers to engage with the policy process. Individual researchers availed of this context to both advance their ideas, and to draw new actors into the field. Copyright © 2013. Published by Elsevier Ltd.

Assessment on Experimental Bacterial Biofilms and in Clinical Practice of the Efficacy of Sampling Solutions for Microbiological Testing of Endoscopes

PubMed Central

Aumeran, C.; Thibert, E.; Chapelle, F. A.; Hennequin, C.; Lesens, O.

2012-01-01

Opinions differ on the value of microbiological testing of endoscopes, which varies according to the technique used. We compared the efficacy on bacterial biofilms of sampling solutions used for the surveillance of the contamination of endoscope channels. To compare efficacy, we used an experimental model of a 48-h Pseudomonas biofilm grown on endoscope internal tubing. Sampling of this experimental biofilm was performed with a Tween 80-lecithin-based solution, saline, and sterile water. We also performed a randomized prospective study during routine clinical practice in our hospital sampling randomly with two different solutions the endoscopes after reprocessing. Biofilm recovery expressed as a logarithmic ratio of bacteria recovered on bacteria initially present in biofilm was significantly more effective with the Tween 80-lecithin-based solution than with saline solution (P = 0.002) and sterile water (P = 0.002). There was no significant difference between saline and sterile water. In the randomized clinical study, the rates of endoscopes that were contaminated with the Tween 80-lecithin-based sampling solution and the saline were 8/25 and 1/25, respectively (P = 0.02), and the mean numbers of bacteria recovered were 281 and 19 CFU/100 ml (P = 0.001), respectively. In conclusion, the efficiency and therefore the value of the monitoring of endoscope reprocessing by microbiological cultures is dependent on the sampling solutions used. A sampling solution with a tensioactive action is more efficient than saline in detecting biofilm contamination of endoscopes. PMID:22170930

Clinical skills assessment of procedural and advanced communication skills: performance expectations of residency program directors.

PubMed

Langenau, Erik E; Zhang, Xiuyuan; Roberts, William L; DeChamplain, Andre F; Boulet, John R

2012-01-01

High stakes medical licensing programs are planning to augment and adapt current examinations to be relevant for a two-decision point model for licensure: entry into supervised practice and entry into unsupervised practice. Therefore, identifying which skills should be assessed at each decision point is critical for informing examination development, and gathering input from residency program directors is important. Using data from previously developed surveys and expert panels, a web-delivered survey was distributed to 3,443 residency program directors. For each of the 28 procedural and 18 advanced communication skills, program directors were asked which clinical skills should be assessed, by whom, when, and how. Descriptive statistics were collected, and Intraclass Correlations (ICC) were conducted to determine consistency across different specialties. Among 347 respondents, program directors reported that all advanced communication and some procedural tasks are important to assess. The following procedures were considered 'important' or 'extremely important' to assess: sterile technique (93.8%), advanced cardiovascular life support (ACLS) (91.1%), basic life support (BLS) (90.0%), interpretation of electrocardiogram (89.4%) and blood gas (88.7%). Program directors reported that most clinical skills should be assessed at the end of the first year of residency (or later) and not before graduation from medical school. A minority were considered important to assess prior to the start of residency training: demonstration of respectfulness (64%), sterile technique (67.2%), BLS (68.9%), ACLS (65.9%) and phlebotomy (63.5%). Results from this study support that assessing procedural skills such as cardiac resuscitation, sterile technique, and phlebotomy would be amenable to assessment at the end of medical school, but most procedural and advanced communications skills would be amenable to assessment at the end of the first year of residency training or later. Gathering

Sarcopenia in Alcoholic Liver Disease: Clinical and Molecular Advances.

PubMed

Dasarathy, Jaividhya; McCullough, Arthur J; Dasarathy, Srinivasan

2017-08-01

Despite advances in treatment of alcohol use disorders that focus on increasing abstinence and reducing recidivism, alcoholic liver disease (ALD) is projected to be the major cause of cirrhosis and its complications. Malnutrition is recognized as the most frequent complication in ALD, and despite the high clinical significance, there are no effective therapies to reverse malnutrition in ALD. Malnutrition is a relatively imprecise term, and sarcopenia or skeletal muscle loss, the major component of malnutrition, is primarily responsible for the adverse clinical consequences in patients with liver disease. It is, therefore, critical to define the specific abnormality (sarcopenia) rather than malnutrition in ALD, so that therapies targeting sarcopenia can be developed. Skeletal muscle mass is maintained by a balance between protein synthesis and proteolysis. Both direct effects of ethanol (EtOH) and its metabolites on the skeletal muscle and the consequences of liver disease result in disturbed proteostasis (protein homeostasis) and consequent sarcopenia. Once cirrhosis develops in patients with ALD, abstinence is unlikely to be effective in completely reversing sarcopenia, as other contributors including hyperammonemia, hormonal, and cytokine abnormalities aggravate sarcopenia and maintain a state of anabolic resistance initiated by EtOH. Cirrhosis is also a state of accelerated starvation, with increased gluconeogenesis that requires amino acid diversion from signaling and substrate functions. Novel therapeutic options are being recognized that are likely to supplant the current "deficiency replacement" approach and instead focus on specific molecular perturbations, given the increasing availability of small molecules that can target specific signaling components. Myostatin antagonists, leucine supplementation, and mitochondrial protective agents are currently in various stages of evaluation in preclinical studies to prevent and reverse sarcopenia, in cirrhosis in

Advance directives outside the USA: are they the best solution everywhere?

PubMed

Sanchez-Gonzalez, M A

1997-09-01

This article evaluates the potential role of advance directives outside of their original North American context. In order to do this, the article first analyses the historical process which has promoted advance directives in recent years. Next, it brings to light certain presuppositions which have given them force: atomistic individualism, contractualism, consumerism and entrepreneurialism, pluralism, proceduralism, and "American moralism." The article next studies certain European cultural peculiarities which could affect advance directives: the importance of virtue versus rights, stoicism versus consumerist utilitarianism, rationalism verus empiricism, statism versus citizens' initiative, and justice versus autonomy. The article concludes by recognising that autonomy has a transcultural value, although it must be balanced with other principles. Advance Directives can have a function in certain cases. But it does not seem adequate to delegate to advance directives more and more medical decisions, and to make them more binding everyday. It is indispensable to develop other decision-making criteria.

Clinical Model for NASH and Advanced Fibrosis in Adult Patients With Diabetes and NAFLD: Guidelines for Referral in NAFLD.

PubMed

Bazick, Jessica; Donithan, Michele; Neuschwander-Tetri, Brent A; Kleiner, David; Brunt, Elizabeth M; Wilson, Laura; Doo, Ed; Lavine, Joel; Tonascia, James; Loomba, Rohit

2015-07-01

Approximately 18 million people in the U.S. have coexisting type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). It is not known who among these patients has nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Therefore, we aimed to determine factors that are associated with both NASH and advanced fibrosis in patients with diabetes and NAFLD in order to identify who should be prioritized for referral to a hepatologist for further diagnostic evaluation and treatment. This study was derived from the NASH Clinical Research Network studies and included 1,249 patients with biopsy-proven NAFLD (including a model development cohort of 346 patients and an independent validation cohort of 100 patients with type 2 diabetes as defined by the American Diabetes Association criteria). Outcome measures were presence of NASH or advanced fibrosis (stage 3 or 4) using cross-validated, by jackknife method, multivariable-adjusted area under the receiver operating characteristic curve (AUROC) and 95% CI. The mean ± SD age and BMI of patients with diabetes and NAFLD was 52.5 ± 10.3 years and 35.8 ± 6.8 kg/m(2), respectively. The prevalence of NASH and advanced fibrosis was 69.2% and 41.0%, respectively. The model for NASH included white race, BMI, waist, alanine aminotransferase (ALT), Aspartate aminotransferase (AST), albumin, HbA1c, HOMA of insulin resistance, and ferritin with an AUROC of 0.80 (95% CI 0.75-0.84, P = 0.007). The specificity, sensitivity, negative predictive values (NPVs), and positive predictive values (PPVs) were 90.0%, 56.8%, 47.7%, and 93.2%, respectively, and the model correctly classified 67% of patients as having NASH. The model for predicting advanced fibrosis included age, Hispanic ethnicity, BMI, waist-to-hip ratio, hypertension, ALT-to-AST ratio, alkaline phosphatase, isolated abnormal alkaline phosphatase, bilirubin (total and direct), globulin, albumin, serum insulin, hematocrit, international normalized ratio, and platelet count with

Physical and chemical stability of reconstituted and diluted dexrazoxane infusion solutions.

PubMed

Zhang, Yan-Ping; Myers, Alan L; Trinh, Van A; Kawedia, Jitesh D; Kramer, Mark A; Benjamin, Robert S; Tran, Hai T

2014-02-01

Dexrazoxane is used clinically to prevent anthracycline-associated cardiotoxicity. Hydrolysis of dexrazoxane prior to reaching the cardiac membranes severely hampers its mode of action; therefore, degradation during the preparation and administration of intravenous dexrazoxane admixtures demands special attention. Moreover, the ongoing national shortage of one dexrazoxane formulation in the United States has forced pharmacies to dispense other commercially available dexrazoxane products. However, the manufacturers' limited stability data restrict the flexibility of dexrazoxane usage in clinical practice. The aims of this study are to determine the physical and chemical stability of reconstituted and diluted solutions of two commercially available dexrazoxane formulations. The stability of two dexrazoxane products, brand and generic name, in reconstituted and intravenous solutions stored at room temperature without light protection in polyvinyl chloride bags was determined. The concentrations of dexrazoxane were measured at predetermined time points up to 24 h using a validated reversed phase high-performance liquid chromatography with ultraviolet detection assay. Brand (B-) and generic (G-) dexrazoxane products, reconstituted in either sterile water or 0.167 M sodium lactate (final concentration of 10 mg/mL), were found stable for at least to 8 h. Infusion solutions of B-dexrazoxane, prepared according to each manufacturer's directions, were stable for at least 24 h and 8 h at 1 mg/mL and 3 mg/mL, respectively. Infusion solutions of G-dexrazoxane, prepared in either 5% dextrose or 0.9% sodium chloride following the manufacturer's guidelines, were also stable for at least 24 h and 8 h at 1 mg/mL and 3 mg/mL, respectively. All tested solutions were found physically stable up to 24 h at room temperature. The stability of dexrazoxane infusion solutions reported herein permits advance preparation of dexrazoxane intravenous admixtures, facilitating

Use of routinely available clinical, nutritional, and functional criteria to classify cachexia in advanced cancer patients.

PubMed

Vigano, Antonio A L; Morais, José A; Ciutto, Lorella; Rosenthall, Leonard; di Tomasso, Jonathan; Khan, Sarah; Olders, Henry; Borod, Manuel; Kilgour, Robert D

2017-10-01

Cachexia is a highly prevalent syndrome in cancer and chronic diseases. However, due to the heterogeneous features of cancer cachexia, its identification and classification challenge clinical practitioners. To determine the clinical relevance of a cancer cachexia classification system in advanced cancer patients. Beginning with the four-stage classification system proposed for cachexia [non-cachexia (NCa), pre-cachexia (PCa), cachexia (Ca) and refractory cachexia (RCa)], we assigned patients to these cachexia stages according to five classification criteria available in clinical practice: 1) biochemistry (high C-reactive protein or leukocytes, or hypoalbuminemia, or anemia), 2) food intake (normal/decreased), weight loss: 3) moderate (≤5%) or 4) significant (>5%/past six months) and 5) performance status (Eastern Cooperative Oncology Group Performance Status ≥ 3). We then determined if symptom severity, body composition changes, functional levels, hospitalizations and survival rates varied significantly across cachexia stages. Two-hundred and ninety-seven advanced cancer patients with primary gastrointestinal and lung tumors were included. Patients were classified into Ca (36%), PCa and RCa (21%, respectively) and NCa (15%). Significant (p < 0.05) differences were observed among cachexia stages for most of the outcome measures (symptoms, body composition, handgrip strength, emergency room visits and length of hospital stays) according to cachexia severity. Survival also differed between cachexia stages (except between PCa and Ca). Five clinical criteria can be used to stage cancer cachexia patients and predict important clinical, nutritional and functional outcomes. The lack of statistical difference between PCa and Ca in almost all clinical outcomes examined suggests either that the PCa group includes patients already affected by early cachexia or that more precise criteria are needed to differentiate PCa from Ca patients. More studies are required to

Development and validation of a clinically applicable score to classify cachexia stages in advanced cancer patients

PubMed Central

Zhou, Ting; Wang, Bangyan; Liu, Huiquan; Yang, Kaixiang; Thapa, Sudip; Zhang, Haowen; Li, Lu

2018-01-01

Abstract Background Cachexia is a multifactorial syndrome that is highly prevalent in advanced cancer patients and leads to progressive functional impairments. The classification of cachexia stages is essential for diagnosing and treating cachexia. However, there is a lack of simple tools with good discrimination for classifying cachexia stages. Therefore, our study aimed to develop a clinically applicable cachexia staging score (CSS) and validate its discrimination of clinical outcomes for different cachexia stages. Methods Advanced cancer patients were enrolled in our study. A CSS comprising the following five components was developed: weight loss, a simple questionnaire of sarcopenia (SARC‐F), Eastern Cooperative Oncology Group, appetite loss, and abnormal biochemistry. According to the CSS, patients were classified into non‐cachexia, pre‐cachexia, cachexia, and refractory cachexia stages, and clinical outcomes were compared among the four groups. Results Of the 297 participating patients, data from 259 patients were ultimately included. Based on the CSS, patients were classified into non‐cachexia (n = 69), pre‐cachexia (n = 68), cachexia (n = 103), and refractory cachexia (n = 19) stages. Patients with more severe cachexia stages had lower skeletal muscle indexes (P = 0.002 and P = 0.004 in male and female patients, respectively), higher prevalence of sarcopenia (P = 0.017 and P = 0.027 in male and female patients, respectively), more severe symptom burden (P < 0.001), poorer quality of life (P < 0.001 for all subscales except social well‐being), and shorter survival times (P < 0.001). Conclusions The CSS is a simple and clinically applicable tool with excellent discrimination for classifying cachexia stages. This score is extremely useful for the clinical treatment and prognosis of cachexia and for designing clinical trials. PMID:29372594

[Discussion on solutions to ethical issues of clinical researches in a real world].

PubMed

Wang, Si-Cheng; Liu, Bao-Yan; Xiong, Ning-Ning; Xie, Qi; Zhang, Run-Shun; Zhou, Xue-Zhong; Qiao, Jie

2013-04-01

The paradigm of a real world study has become the frontiers of clinical researches, especially in the field of Chinese medicine, all over the world in recent years. In this paper, ethical issues which probably exist in real-world studies are raised and reviewed. Moreover, some preliminary solutions to these issues such as protecting subjects during the process of real-world studies and performing ethical review are raised based on recent years' practices to enhance the scientificity and ethical level of real-world studies.

Five-Year Longitudinal Assessment (2008 to 2012) of E-101 Solution Activity against Clinical Target and Antimicrobial-Resistant Pathogens

PubMed Central

Pillar, Chris M.; Sahm, Daniel F.; O'Hanley, Peter; Stephens, Jackson T.

2014-01-01

This study summarizes the topical E-101 solution susceptibility testing results for 760 Gram-positive and Gram-negative target pathogens collected from 75 U.S. sites between 2008 and 2012 and 103 ESKAPE pathogens. E-101 solution maintained potent activity against all bacterial species studied for each year tested, with MICs ranging from <0.008 to 0.25 μg porcine myeloperoxidase (pMPO)/ml. These results confirm that E-101 solution retains its potent broad-spectrum activity against U.S. clinical isolates and organisms with challenging resistance phenotypes. PMID:24841272

Using Technology, Clinical Workflow Redesign, and Team Solutions to Achieve the Patient Centered Medical Home

DTIC Science & Technology

2011-01-01

The Quadruple Aim: Working Together, Achieving Success 2011 Military Health System Conference TMA and Services Using Technology, Clinical Workflow...Redesign, and Team Solutions to Achieve the Patient Centered Medical Home LTC Nicole Kerkenbush, MHA, MN Army Medical Department, Office of the...Surgeon General Chief Medical Information Officer 1 Military Health System Conference Report Documentation Page Form ApprovedOMB No. 0704-0188 Public

Advancing Porous Silicon Biosensor Technology for Use in Clinical Diagnostics

NASA Astrophysics Data System (ADS)

Bonanno, Lisa Marie

Inexpensive and robust analytical techniques for detecting molecular recognition events are in great demand in healthcare, food safety, and environmental monitoring. Despite vast research in this area, challanges remain to develop practical biomolecular platforms that, meet the rigorous demands of real-world applications. This includes maintaining low-cost devices that are sensitive and specific in complex test specimens, are stable after storage, have short assay time, and possess minimal complexity of instrumentation for readout. Nanostructured porous silicon (PSi) material has been identified as an ideal candidate towards achieving these goals and the past decade has seen diverse proof-of-principle studies developing optical-based sensing techniques. In Part 1 of this thesis, the impact of surface chemistry and PSi morphology on detection sensitivity of target molecules is investigated. Initial proof-of-concept that PSi devices facilitate detection of protein in whole blood is demonstrated. This work highlights the importance of material stability and blocking chemistry for sensor use in real world biological samples. In addition, the intrinisic filtering capability of the 3-D PSi morphology is shown as an advantage in complex solutions, such as whole blood. Ultimately, this initial work identified a need to improve detection sensitivity of the PSI biosensor technique to facilitate clinical diagnostic use over relevant target concentration ranges. The second part of this thesis, builds upon sensitivity challenges that are highlighted in the first part of the thesis and development of a surface-bound competitive inhibition immunoassay facilitated improved detection sensitivity of small molecular weight targets (opiates) over a relevant clinical concentration range. In addition, optimization of assay protocol addressed issues of maintaining stability of sensors after storage. Performance of the developed assay (specificity and sensitivity) was then validated in a

Management of pain in patients with temporomandibular disorder (TMD): challenges and solutions

PubMed Central

Gil-Martínez, Alfonso; Paris-Alemany, Alba; López-de-Uralde-Villanueva, Ibai; La Touche, Roy

2018-01-01

Thanks to advances in neuroscience, biopsychosocial models for diagnostics and treatment (including physical, psychological, and pharmacological therapies) currently have more clinical support and scientific growth. At present, a conservative treatment approach prevails over surgery, given it is less aggressive and usually results in satisfactory clinical outcomes in mild–moderate temporomandibular disorder (TMD). The aim of this review is to evaluate the recent evidence, identify challenges, and propose solutions from a clinical point of view for patients with craniofacial pain and TMD. The treatment we propose is structured in a multi-modal approach based on a biobehavioral approach that includes medical, physiotherapeutic, psychological, and dental treatments. We also propose a new biobehavioral model regarding pain perception and motor behavior for the diagnosis and treatment of patients with painful TMD. PMID:29588615

Advances in the Immunobiological Therapies for Advanced Melanoma.

PubMed

Pérez Gago, M C; Saavedra Santa Gadea, O; de la Cruz-Merino, L

2017-10-01

Metastatic or locally advanced unresectable melanoma carries a high morbidity and mortality. However, notable advances have been made in recent years in the systemic treatment of this disease, with the appearance of targeted therapy using tyrosine kinase inhibitors that block the mitogen activated protein kinase pathway, and of modern immunotherapy with immune-modulating monoclonal antibodies. In this paper, we provide an update of available data on new immune therapies and we review the clinical development that led to their approval for use in routine clinical practice. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Clinical specialists and advanced practitioners in physical therapy: a survey of physical therapists and employers of physical therapists in ontario, Canada.

PubMed

Yardley, Darryl; Gordon, Robert; Freeburn, Ryan; So, Colleen; Beauchamp, David; Landry, Michel D; Switzer-McIntyre, Sharon; Evans, Cathy; Brooks, Dina

2008-01-01

Opportunities to expand the role of physical therapists (PTs) have evolved to include clinical specialists and advanced practitioners, although the literature on these roles is limited. We examined perceptions of PTs and PT employers in Ontario regarding clinical specialization and advanced practice. Using a modified Dillman approach, a cross-sectional survey was conducted with 500 PTs and 500 PT employers in Ontario. Questionnaires were tailored to address specific issues related to each cohort. Sixty percent of PTs and 53% of PT employers responded to the survey. Thirty-three percent of PT respondents already considered themselves "clinical specialists" (CS), and 8% considered themselves "advanced practitioners" (AP), although neither role is yet formally recognized in Canada. Both groups had substantial interest in pursuing formal recognition of CS and AP status. Respondents indicated that their primary motivation to pursue such roles was to enhance clinical reasoning skills with the goal of improving client outcomes (82% for the role of CS, 71% for the role of AP). Respondents supported the involvement of academic institutions in the process (60% for CS, 70% for AP). PTs and PT employers are supportive of the roles of the CS and AP within the profession, even though there is currently no formal recognition of either role in Canada.

How novice, skilled and advanced clinical researchers include variables in a case report form for clinical research: a qualitative study.

PubMed

Chu, Hongling; Zeng, Lin; Fetters, Micheal D; Li, Nan; Tao, Liyuan; Shi, Yanyan; Zhang, Hua; Wang, Xiaoxiao; Li, Fengwei; Zhao, Yiming

2017-09-18

Despite varying degrees in research training, most academic clinicians are expected to conduct clinical research. The objective of this research was to understand how clinical researchers of different skill levels include variables in a case report form for their clinical research. The setting for this research was a major academic institution in Beijing, China. The target population was clinical researchers with three levels of experience, namely, limited clinical research experience, clinicians with rich clinical research experience and clinical research experts. Using a qualitative approach, we conducted 13 individual interviews (face to face) and one group interview (n=4) with clinical researchers from June to September 2016. Based on maximum variation sampling to identify researchers with three levels of research experience: eight clinicians with limited clinical research experience, five clinicians with rich clinical research experience and four clinical research experts. These 17 researchers had diverse hospital-based medical specialties and or specialisation in clinical research. Our analysis yields a typology of three processes developing a case report form that varies according to research experience level. Novice clinician researchers often have an incomplete protocol or none at all, and conduct data collection and publication based on a general framework. Experienced clinician researchers include variables in the case report form based on previous experience with attention to including domains or items at risk for omission and by eliminating unnecessary variables. Expert researchers consider comprehensively in advance data collection and implementation needs and plan accordingly. These results illustrate increasing levels of sophistication in research planning that increase sophistication in selection for variables in the case report form. These findings suggest that novice and intermediate-level researchers could benefit by emulating the comprehensive

Physicochemical characterization and water vapor sorption of organic solution advanced spray-dried inhalable trehalose microparticles and nanoparticles for targeted dry powder pulmonary inhalation delivery.

PubMed

Li, Xiaojian; Mansour, Heidi M

2011-12-01

Novel advanced spray-dried inhalable trehalose microparticulate/nanoparticulate powders with low water content were successfully produced by organic solution advanced spray drying from dilute solution under various spray-drying conditions. Laser diffraction was used to determine the volumetric particle size and size distribution. Particle morphology and surface morphology was imaged and examined by scanning electron microscopy. Hot-stage microscopy was used to visualize the presence/absence of birefringency before and following particle engineering design pharmaceutical processing, as well as phase transition behavior upon heating. Water content in the solid state was quantified by Karl Fisher (KF) coulometric titration. Solid-state phase transitions and degree of molecular order were examined by differential scanning calorimetry (DSC) and powder X-ray diffraction, respectively. Scanning electron microscopy showed a correlation between particle morphology, surface morphology, and spray drying pump rate. All advanced spray-dried microparticulate/nanoparticulate trehalose powders were in the respirable size range and exhibited a unimodal distribution. All spray-dried powders had very low water content, as quantified by KF. The absence of crystallinity in spray-dried particles was reflected in the powder X-ray diffractograms and confirmed by thermal analysis. DSC thermal analysis indicated that the novel advanced spray-dried inhalable trehalose microparticles and nanoparticles exhibited a clear glass transition (T(g)). This is consistent with the formation of the amorphous glassy state. Spray-dried amorphous glassy trehalose inhalable microparticles and nanoparticles exhibited vapor-induced (lyotropic) phase transitions with varying levels of relative humidity as measured by gravimetric vapor sorption at 25°C and 37°C.

Basic and Clinical Research Against Advanced Glycation End Products (AGEs): New Compounds to Tackle Cardiovascular Disease and Diabetic Complications.

PubMed

Nenna, Antonio; Spadaccio, Cristiano; Lusini, Mario; Ulianich, Luca; Chello, Massimo; Nappi, Francesco

2015-01-01

Diabetes is a major risk factor for cardiovascular disease, and recent advances in research indicate that a detailed understanding of the pathophysiology of its effects is mandatory to reduce diabetes-related mortality and morbidity. Advanced Glycation End Products (AGEs) play a central role in the genesis and progression of complications of both type 1 and type 2 diabetes mellitus, and have been found to be important even in non-diabetic patients as a marker of cardiovascular disease. AGEs have a profound impact on patient's prognosis regardless of the glycemic control, and therefore pharmacologic approaches against AGEs accumulation have been proposed over the years to treat cardiovascular diseases, parallel to a more detailed understanding of AGEs pathophysiology. Compounds with anti-AGEs effects are currently under investigation in both pre-clinical and clinical scenarios, and many of the drugs previously used to treat specific diseases have been found to have AGE-inhibitory effects. Some products are still in "bench evaluation", whereas others have been already investigated in clinical trials with conflicting evidences. This review aims at summarizing the mechanisms of AGEs formation and accumulation, and the most relevant issues in pre-clinical and clinical experiences in anti-AGEs treatment in cardiovascular research.

Analyzing clinical phonological data using Phon

PubMed Central

McAllister Byun, Tara

2016-01-01

In this paper, we describe how Phon, a software program for the transcription and analysis of phonological data, can be applied to facilitate clinical phonological analyses. We begin with a summary of the types of analyses that are frequently used in the assessment and management of speech sound disorders. We then discuss challenges inherent to the transcription and analysis of clinical phonological data. For each challenge, we discuss solutions currently available within Phon, and offer an outlook on future methodological and technical developments in the area of clinical phonology. This paper includes a step-by-step introduction to Phon suitable for readers who lack previous experience with the software. We conclude with a discussion of data sharing and its vital role in advancing research and intervention practices in the area of speech development and disorders. PMID:27111269

Leveraging electronic health records for clinical research.

PubMed

Raman, Sudha R; Curtis, Lesley H; Temple, Robert; Andersson, Tomas; Ezekowitz, Justin; Ford, Ian; James, Stefan; Marsolo, Keith; Mirhaji, Parsa; Rocca, Mitra; Rothman, Russell L; Sethuraman, Barathi; Stockbridge, Norman; Terry, Sharon; Wasserman, Scott M; Peterson, Eric D; Hernandez, Adrian F

2018-04-30

Electronic health records (EHRs) can be a major tool in the quest to decrease costs and timelines of clinical trial research, generate better evidence for clinical decision making, and advance health care. Over the past decade, EHRs have increasingly offered opportunities to speed up, streamline, and enhance clinical research. EHRs offer a wide range of possible uses in clinical trials, including assisting with prestudy feasibility assessment, patient recruitment, and data capture in care delivery. To fully appreciate these opportunities, health care stakeholders must come together to face critical challenges in leveraging EHR data, including data quality/completeness, information security, stakeholder engagement, and increasing the scale of research infrastructure and related governance. Leaders from academia, government, industry, and professional societies representing patient, provider, researcher, industry, and regulator perspectives convened the Leveraging EHR for Clinical Research Now! Think Tank in Washington, DC (February 18-19, 2016), to identify barriers to using EHRs in clinical research and to generate potential solutions. Think tank members identified a broad range of issues surrounding the use of EHRs in research and proposed a variety of solutions. Recognizing the challenges, the participants identified the urgent need to look more deeply at previous efforts to use these data, share lessons learned, and develop a multidisciplinary agenda for best practices for using EHRs in clinical research. We report the proceedings from this think tank meeting in the following paper. Copyright © 2018 Elsevier, Inc. All rights reserved.

A model-driven approach for representing clinical archetypes for Semantic Web environments.

PubMed

Martínez-Costa, Catalina; Menárguez-Tortosa, Marcos; Fernández-Breis, Jesualdo Tomás; Maldonado, José Alberto

2009-02-01

The life-long clinical information of any person supported by electronic means configures his Electronic Health Record (EHR). This information is usually distributed among several independent and heterogeneous systems that may be syntactically or semantically incompatible. There are currently different standards for representing and exchanging EHR information among different systems. In advanced EHR approaches, clinical information is represented by means of archetypes. Most of these approaches use the Archetype Definition Language (ADL) to specify archetypes. However, ADL has some drawbacks when attempting to perform semantic activities in Semantic Web environments. In this work, Semantic Web technologies are used to specify clinical archetypes for advanced EHR architectures. The advantages of using the Ontology Web Language (OWL) instead of ADL are described and discussed in this work. Moreover, a solution combining Semantic Web and Model-driven Engineering technologies is proposed to transform ADL into OWL for the CEN EN13606 EHR architecture.

Clinical grade adult stem cell banking

PubMed Central

Thirumala, Sreedhar; Goebel, W Scott

2009-01-01

There has been a great deal of scientific interest recently generated by the potential therapeutic applications of adult stem cells in human care but there are several challenges regarding quality and safety in clinical applications and a number of these challenges relate to the processing and banking of these cells ex-vivo. As the number of clinical trials and the variety of adult cells used in regenerative therapy increases, safety remains a primary concern. This has inspired many nations to formulate guidelines and standards for the quality of stem cell collection, processing, testing, banking, packaging and distribution. Clinically applicable cryopreservation and banking of adult stem cells offers unique opportunities to advance the potential uses and widespread implementation of these cells in clinical applications. Most current cryopreservation protocols include animal serum proteins and potentially toxic cryoprotectant additives (CPAs) that prevent direct use of these cells in human therapeutic applications. Long term cryopreservation of adult stem cells under good manufacturing conditions using animal product free solutions is critical to the widespread clinical implementation of ex-vivo adult stem cell therapies. Furthermore, to avoid any potential cryoprotectant related complications, reduced CPA concentrations and efficient post-thaw washing to remove CPA are also desirable. The present review focuses on the current strategies and important aspects of adult stem cell banking for clinical applications. These include current good manufacturing practices (cGMPs), animal protein free freezing solutions, cryoprotectants, freezing & thawing protocols, viability assays, packaging and distribution. The importance and benefits of banking clinical grade adult stem cells are also discussed. PMID:20046678

Comparison of different advanced oxidation processes for the degradation of two fluoroquinolone antibiotics in aqueous solutions.

PubMed

Bobu, Maria; Yediler, Ayfer; Siminiceanu, Ilie; Zhang, Feifang; Schulte-Hostede, Sigurd

2013-01-01

In this study a comparative assessment using various advanced oxidation processes (UV/H(2)O(2), UV/H(2)O(2)/Fe(II), O(3), O(3)/UV, O(3)/UV/H(2)O(2) and O(3)/UV/H(2)O(2)/Fe(II)) was attempted to degrade efficiently two fluoroquinolone drugs ENR [enrofloxacin (1-Cyclopropyl-7-(4-ethyl-1-piperazinyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolonecarboxylic acid)] and CIP [ciprofloxacin (1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-quinoline-3-carboxylic acid)] in aqueous solutions at a concentrations of 0.15 mM for each drug. The efficiency of the applied oxidation processes (AOPs) has been estimated by the conversion of the original substrate (X(ENR) and X(CIP)) and the reduction of chemical oxygen demand (COD), total organic carbon (TOC). Special emphasis was laid on the effect of varying reaction pH as well as of the applied oxidant doses on the observed reaction kinetics for each advanced oxidation processes. High degradation efficiencies, particularly in terms of rates of TOC and COD abatement, were obtained for photo-Fenton assisted ozonation [O(3)/UV/H(2)O(2)/Fe(II)], compared to other advanced oxidation processes. At pH 3 and 25°C best results for the degradation of both investigated drugs were achieved when 10 mM H(2)O(2), 0.5 mM Fe(II) and an initial dose of 8.5 mg L(-1) ozone were applied. In addition, the evolution of toxicity of the reaction mixtures for different AOPs has been studied by the bioluminescence test (LUMIStox 300).

Advancing Psychologically Informed Practice for Patients With Persistent Musculoskeletal Pain: Promise, Pitfalls, and Solutions.

PubMed

Keefe, Francis J; Main, Chris J; George, Steven Z

2018-05-01

There has been growing interest in psychologically oriented pain management over the past 3 to 4 decades, including a 2011 description of psychologically informed practice (PIP) for low back pain. PIP requires a broader focus than traditional biomechanical and pathology-based approaches that have been traditionally used to manage musculoskeletal pain. A major focus of PIP is addressing the behavioral aspects of pain (ie, peoples' responses to pain) by identifying individual expectations, beliefs, and feelings as prognostic factors for clinical and occupational outcomes indicating progression to chronicity. Since 2011, the interest in PIP seems to be growing, as evidenced by its use in large trials, inclusion in scientific conferences, increasing evidence base, and expansion to other musculoskeletal pain conditions. Primary care physicians and physical therapists have delivered PIP as part of a stratified care approach involving screening and targeting of treatment for people at high risk for continued pain-associated disability. Furthermore, PIP is consistent with recent national priorities emphasizing nonpharmacological pain management options. In this perspective, PIP techniques that range in complexity are described, considerations for implementation in clinical practice are offered, and future directions that will advance the understanding of PIP are outlined.

Classical Electrodynamics: Problems with solutions; Problems with solutions

NASA Astrophysics Data System (ADS)

Likharev, Konstantin K.

2018-06-01

l Advanced Physics is a series comprising four parts: Classical Mechanics, Classical Electrodynamics, Quantum Mechanics and Statistical Mechanics. Each part consists of two volumes, Lecture notes and Problems with solutions, further supplemented by an additional collection of test problems and solutions available to qualifying university instructors. This volume, Classical Electrodynamics: Lecture notes is intended to be the basis for a two-semester graduate-level course on electricity and magnetism, including not only the interaction and dynamics charged point particles, but also properties of dielectric, conducting, and magnetic media. The course also covers special relativity, including its kinematics and particle-dynamics aspects, and electromagnetic radiation by relativistic particles.

Diquafosol sodium ophthalmic solution for the treatment of dry eye: clinical evaluation and biochemical analysis of tear composition.

PubMed

Shigeyasu, Chika; Yamada, Masakazu; Akune, Yoko; Tsubota, Kazuo

2015-11-01

To evaluate the clinical efficacy of 3% diquafosol sodium ophthalmic solution for dry eye, and to analyze the concentration of tear proteins and mucin-like substances after the treatment. Fifty eyes of 25 patients with dry eye syndrome were prospectively enrolled. The patients were treated with diquafosol solution at a dose of 1 drop in each eye 6 times daily for 4 weeks. The parameters of clinical efficacy were tear osmolarity, tear breakup time (BUT), fluorescein staining scores for the cornea and conjunctiva, Schirmer test values, and subjective symptoms evaluated using the ocular surface disease index (OSDI). Tears collected with Schirmer test strips were analyzed by high-performance liquid chromatography, and the concentrations of the total protein and the 4 major tear proteins, namely, secretory IgA, lactoferrin, lipocalin-1, lysozyme, and N-acetyl-neuraminic acid (Neu5Ac), were measured. Neu5Ac is a major sialic acid, a marker of secretory mucins. The BUT, keratoconjunctival staining scores, and Schirmer test values were improved with statistical significance after the treatment with diquafosol solution, while changes in the other parameters, including tear osmolarity, corneal staining scores, and OSDI scores were not significant. The Neu5Ac concentration was significantly increased, which was not accompanied by changes in tear proteins. Topical application of diquafosol significantly improved the clinical parameters of the BUT, keratoconjunctival staining scores, and Schirmer test values and was accompanied by increased sialic acid content in the tears of patients with dry eye.

An affordable cuff-less blood pressure estimation solution.

PubMed

Jain, Monika; Kumar, Niranjan; Deb, Sujay

2016-08-01

This paper presents a cuff-less hypertension pre-screening device that non-invasively monitors the Blood Pressure (BP) and Heart Rate (HR) continuously. The proposed device simultaneously records two clinically significant and highly correlated biomedical signals, viz., Electrocardiogram (ECG) and Photoplethysmogram (PPG). The device provides a common data acquisition platform that can interface with PC/laptop, Smart phone/tablet and Raspberry-pi etc. The hardware stores and processes the recorded ECG and PPG in order to extract the real-time BP and HR using kernel regression approach. The BP and HR estimation error is measured in terms of normalized mean square error, Error Standard Deviation (ESD) and Mean Absolute Error (MAE), with respect to a clinically proven digital BP monitor (OMRON HBP1300). The computed error falls under the maximum standard allowable error mentioned by Association for the Advancement of Medical Instrumentation; MAE <; 5 mmHg and ESD <; 8mmHg. The results are validated using two-tailed dependent sample t-test also. The proposed device is a portable low-cost home and clinic bases solution for continuous health monitoring.

Clinical roundtable monograph: new and emerging treatments for advanced prostate cancer.

PubMed

George, Daniel J; Kantoff, Philip W; Lin, Daniel W

2011-06-01

Historically, the treatment of metastatic castration-resistant prostate cancer (CRPC) has been limited to chemotherapeutic regimens that did not improve patient survival. In 2004, clinical studies began to demonstrate significant improvements in patient outcomes, including overall survival, with docetaxel versus mitoxantrone chemotherapy. Since these pivotal trials, the combination of docetaxel plus prednisone has become a standard of care for patients with metastatic CRPC. However, the limited survival benefit achieved with this regimen prompted several investigations into the development of alternative therapeutic options. Recent advances have now led to an unprecedented number of new drug approvals within the past year, providing many new treatment options for patients with metastatic CRPC. Sipuleucel-T, considered a new paradigm in cancer treatment, is the first such immunotherapeutic agent approved by the US Food and Drug Administration. Other successes include abiraterone acetate, the first androgen biosynthesis inhibitor, and cabazitaxel, a novel microtubule inhibitor, both of which have demonstrated improved survival following docetaxel failure. The bone-targeting agent denosumab, also recently approved in this setting, offers these patients significant improvement in the prevention of skeletal-related events. The data supporting the approval of each of these agents are described in this monograph, as are current approaches in the treatment of metastatic CRPC and ongoing clinical trials of novel treatments and strategies. The experts also discuss several of the issues regarding the introduction of these novel agents into clinical practice for metastatic CRPC patients.

Advanced glycation end products in clinical nephrology.

PubMed

Kalousová, M; Zima, T; Tesar, V; Stípek, S; Sulková, S

2004-01-01

As a result of oxidative and carbonyl stress, advanced glycation end products (AGEs) are involved in the pathogenesis of severe and frequent diseases and their fatal vascular/cardiovascular complications, i.e. diabetes mellitus and its complications (nephropathy, angiopathy, neuropathy and retinopathy, renal failure and uremic and dialysis-associated complications), atherosclerosis and dialysis-related amyloidosis, neurodegenerative diseases, and rheumatoid arthritis. They are formed via non-enzymatic glycation which is specifically enhanced through the presence of oxidative and carbonyl stress, and their ability to form glycoxidation products in peptide and protein structures finally modulating or inducing biological reactivity. Food can be another source of AGEs; however, high serum AGEs in hemodialysis patients might reflect nutritional status better. Several methods of renal replacement therapy have been studied in connection with the AGE removal, but unfortunately the possibilities are still unsatisfactory even if high flux dialysis, hemofiltration, or hemodiafiltration give better results than conventional low flux dialysis. AGEs are currently being studied in the patients on peritoneal dialysis as their precursors can be formed in the dialysis fluid. AGEs can cause damage to the peritoneum and so a loss of ultrafiltration capacity. Many compounds give promising results in AGE inhibition (inhibition of formation of AGEs, inhibition of their action or degradation of AGEs), are tested for these properties, and eventually undergo clinical studies (e.g. aminoguanidine, OPB-9195, pyridoxamine, antioxidants, N-phenacylthiazolium bromide, antihypertensive drugs, angiotensin-converting enzyme inhibitors and angiotensin II receptor-1 antagonists). Copyright 2004 S. Karger AG, Basel

A review of Raman spectroscopy advances with an emphasis on clinical translation challenges in oncology

NASA Astrophysics Data System (ADS)

Jermyn, Michael; Desroches, Joannie; Aubertin, Kelly; St-Arnaud, Karl; Madore, Wendy-Julie; De Montigny, Etienne; Guiot, Marie-Christine; Trudel, Dominique; Wilson, Brian C.; Petrecca, Kevin; Leblond, Frederic

2016-12-01

There is an urgent need for improved techniques for disease detection. Optical spectroscopy and imaging technologies have potential for non- or minimally-invasive use in a wide range of clinical applications. The focus here, in vivo Raman spectroscopy (RS), measures inelastic light scattering based on interaction with the vibrational and rotational modes of common molecular bonds in cells and tissue. The Raman ‘signature’ can be used to assess physiological status and can also be altered by disease. This information can supplement existing diagnostic (e.g. radiological imaging) techniques for disease screening and diagnosis, in interventional guidance for identifying disease margins, and in monitoring treatment responses. Using fiberoptic-based light delivery and collection, RS is most easily performed on accessible tissue surfaces, either on the skin, in hollow organs or intra-operatively. The strength of RS lies in the high biochemical information content of the spectra, that characteristically show an array of very narrow peaks associated with specific chemical bonds. This results in high sensitivity and specificity, for example to distinguish malignant or premalignant from normal tissues. A critical issue is that the Raman signal is often very weak, limiting clinical use to point-by-point measurements. However, non-linear techniques using pulsed-laser sources have been developed to enable in vivo Raman imaging. Changes in Raman spectra with disease are often subtle and spectrally distributed, requiring full spectral scanning, together with the use of tissue classification algorithms that must be trained on large numbers of independent measurements. Recent advances in instrumentation and spectral analysis have substantially improved the clinical feasibility of RS, so that it is now being investigated with increased success in a wide range of cancer types and locations, as well as for non-oncological conditions. This review covers recent advances and

Comparison of different advanced degradation processes for the removal of the pharmaceutical compounds diclofenac and carbamazepine from liquid solutions.

PubMed

Capodaglio, Andrea G; Bojanowska-Czajka, Anna; Trojanowicz, Marek

2018-04-18

Carbamazepine and diclofenac are two examples of drugs with widespread geographical and environmental media proliferation that are poorly removed by traditional wastewater treatment processes. Advanced oxidation processes (AOPs) have been proposed as alternative methods to remove these compounds in solution. AOPs are based on a wide class of powerful technologies, including UV radiation, ozone, hydrogen peroxide, Fenton process, catalytic wet peroxide oxidation, heterogeneous photocatalysis, electrochemical oxidation and their combinations, sonolysis, and microwaves applicable to both water and wastewater. Moreover, processes rely on the production of oxidizing radicals (•OH and others) in a solution to decompose present pollutants. Water radiolysis-based processes, which are an alternative to the former, involve the use of concentrated energy (beams of accelerated electrons or γ-rays) to split water molecules, generating strong oxidants and reductants (radicals) at the same time. In this paper, the degradation of carbamazepine and diclofenac by means of all these processes is discussed and compared. Energy and byproduct generation issues are also addressed.

Clinical skills assessment of procedural and advanced communication skills: performance expectations of residency program directors

PubMed Central

Langenau, Erik E.; Zhang, Xiuyuan; Roberts, William L.; DeChamplain, Andre F.; Boulet, John R.

2012-01-01

Background High stakes medical licensing programs are planning to augment and adapt current examinations to be relevant for a two-decision point model for licensure: entry into supervised practice and entry into unsupervised practice. Therefore, identifying which skills should be assessed at each decision point is critical for informing examination development, and gathering input from residency program directors is important. Methods Using data from previously developed surveys and expert panels, a web-delivered survey was distributed to 3,443 residency program directors. For each of the 28 procedural and 18 advanced communication skills, program directors were asked which clinical skills should be assessed, by whom, when, and how. Descriptive statistics were collected, and Intraclass Correlations (ICC) were conducted to determine consistency across different specialties. Results Among 347 respondents, program directors reported that all advanced communication and some procedural tasks are important to assess. The following procedures were considered ‘important’ or ‘extremely important’ to assess: sterile technique (93.8%), advanced cardiovascular life support (ACLS) (91.1%), basic life support (BLS) (90.0%), interpretation of electrocardiogram (89.4%) and blood gas (88.7%). Program directors reported that most clinical skills should be assessed at the end of the first year of residency (or later) and not before graduation from medical school. A minority were considered important to assess prior to the start of residency training: demonstration of respectfulness (64%), sterile technique (67.2%), BLS (68.9%), ACLS (65.9%) and phlebotomy (63.5%). Discussion Results from this study support that assessing procedural skills such as cardiac resuscitation, sterile technique, and phlebotomy would be amenable to assessment at the end of medical school, but most procedural and advanced communications skills would be amenable to assessment at the end of the first

Advanced practice nursing role delineation in acute and critical care: application of the strong model of advanced practice.

PubMed

Mick, D J; Ackerman, M H

2000-01-01

This purpose of this study was to differentiate between the roles of clinical nurse specialists and acute care nurse practitioners. Hypothesized blending of the clinical nurse specialist and acute care nurse practitioner roles is thought to result in an acute care clinician who integrates the clinical skills of the nurse practitioner with the systems knowledge, educational commitment, and leadership ability of the clinical nurse specialist. Ideally, this role blending would facilitate excellence in both direct and indirect patient care. The Strong Model of Advanced Practice, which incorporates practice domains of direct comprehensive care, support of systems, education, research, and publication and professional leadership, was tested to search for practical evidence of role blending. This descriptive, exploratory, pilot study included subjects (N = 18) solicited from an academic medical center and from an Internet advanced practice listserv. Questionnaires included self-ranking of expertise in practice domains, as well as valuing of role-related tasks. Content validity was judged by an expert panel of advanced practice nurses. Analyses of descriptive statistics revealed that clinical nurse specialists, who had more experience both as registered nurses and in the advanced practice nurse role, self-ranked their expertise higher in all practice domains. Acute care nurse practitioners placed higher importance on tasks related to direct comprehensive care, including conducting histories and physicals, diagnosing, and performing diagnostic procedures, whereas clinical nurse specialists assigned greater importance to tasks related to education, research, and leadership. Levels of self-assessed clinical expertise as well as valuing of role-related tasks differed among this sample of clinical nurse specialists and acute care nurse practitioners. Groundwork has been laid for continuing exploration into differentiation in advanced practice nursing roles. As the clinical

Advancing clinical reasoning in virtual patients – development and application of a conceptual framework

PubMed Central

Hege, Inga; Kononowicz, Andrzej A.; Berman, Norman B.; Lenzer, Benedikt; Kiesewetter, Jan

2018-01-01

Background: Clinical reasoning is a complex skill students have to acquire during their education. For educators it is difficult to explain their reasoning to students, because it is partly an automatic and unconscious process. Virtual Patients (VPs) are used to support the acquisition of clinical reasoning skills in healthcare education. However, until now it remains unclear which features or settings of VPs optimally foster clinical reasoning. Therefore, our aims were to identify key concepts of the clinical reasoning process in a qualitative approach and draw conclusions on how each concept can be enhanced to advance the learning of clinical reasoning with virtual patients. Methods: We chose a grounded theory approach to identify key categories and concepts of learning clinical reasoning and develop a framework. Throughout this process, the emerging codes were discussed with a panel of interdisciplinary experts. In a second step we applied the framework to virtual patients. Results: Based on the data we identified the core category as the "multifactorial nature of learning clinical reasoning". This category is reflected in the following five main categories: Psychological Theories, Patient-centeredness, Context, Learner-centeredness, and Teaching/Assessment. Each category encompasses between four and six related concepts. Conclusions: With our approach we were able to elaborate how key categories and concepts of clinical reasoning can be applied to virtual patients. This includes aspects such as allowing learners to access a large number of VPs with adaptable levels of complexity and feedback or emphasizing dual processing, errors, and uncertainty. PMID:29497697

Clinical Specialists and Advanced Practitioners in Physical Therapy: A Survey of Physical Therapists and Employers of Physical Therapists in Ontario, Canada

PubMed Central

Gordon, Robert; Freeburn, Ryan; So, Colleen; Beauchamp, David; Landry, Michel D.; Switzer-McIntyre, Sharon; Evans, Cathy; Brooks, Dina

2008-01-01

Purpose: Opportunities to expand the role of physical therapists (PTs) have evolved to include clinical specialists and advanced practitioners, although the literature on these roles is limited. We examined perceptions of PTs and PT employers in Ontario regarding clinical specialization and advanced practice. Methods: Using a modified Dillman approach, a cross-sectional survey was conducted with 500 PTs and 500 PT employers in Ontario. Questionnaires were tailored to address specific issues related to each cohort. Results: Sixty percent of PTs and 53% of PT employers responded to the survey. Thirty-three percent of PT respondents already considered themselves “clinical specialists” (CS), and 8% considered themselves “advanced practitioners” (AP), although neither role is yet formally recognized in Canada. Both groups had substantial interest in pursuing formal recognition of CS and AP status. Respondents indicated that their primary motivation to pursue such roles was to enhance clinical reasoning skills with the goal of improving client outcomes (82% for the role of CS, 71% for the role of AP). Respondents supported the involvement of academic institutions in the process (60% for CS, 70% for AP). Conclusion: PTs and PT employers are supportive of the roles of the CS and AP within the profession, even though there is currently no formal recognition of either role in Canada. PMID:20145755

What can Natural Language Processing do for Clinical Decision Support?

PubMed Central

Demner-Fushman, Dina; Chapman, Wendy W.; McDonald, Clement J.

2009-01-01

Computerized Clinical Decision Support (CDS) aims to aid decision making of health care providers and the public by providing easily accessible health-related information at the point and time it is needed. Natural Language Processing (NLP) is instrumental in using free-text information to drive CDS, representing clinical knowledge and CDS interventions in standardized formats, and leveraging clinical narrative. The early innovative NLP research of clinical narrative was followed by a period of stable research conducted at the major clinical centers and a shift of mainstream interest to biomedical NLP. This review primarily focuses on the recently renewed interest in development of fundamental NLP methods and advances in the NLP systems for CDS. The current solutions to challenges posed by distinct sublanguages, intended user groups, and support goals are discussed. PMID:19683066

Unequal Burden of Disease, Unequal Participation in Clinical Trials: Solutions from African American and Latino Community Members

ERIC Educational Resources Information Center

Ford, Marvella E.; Siminoff, Laura A.; Pickelsimer, Elisabeth; Mainous, Arch G.; Smith, Daniel W.; Diaz, Vanessa A.; Soderstrom, Lea H.; Jefferson, Melanie S.; Tilley, Barbara C.

2013-01-01

African Americans and Latinos are underrepresented in clinical trials. The purpose of this study was to elicit solutions to participation barriers from African Americans and Latinos. Fifty-seven adults (32 African Americans, 25 Latinos) ages 50 years and older participated. The Institute of Medicine's "Unequal Treatment" conceptual framework was…

Design, characterization, and aerosolization of organic solution advanced spray-dried moxifloxacin and ofloxacin dipalmitoylphosphatidylcholine (DPPC) microparticulate/nanoparticulate powders for pulmonary inhalation aerosol delivery

PubMed Central

Duan, Jinghua; Vogt, Frederick G; Li, Xiaojian; Hayes, Don; Mansour, Heidi M

2013-01-01

The aim of this study was to design and develop respirable antibiotics moxifloxacin (MOXI) hydrochloride and ofloxacin (OFLX) microparticles and nanoparticles, and multifunctional antibiotics particles with or without lung surfactant 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) for targeted dry powder inhalation delivery as a pulmonary nanomedicine. Particles were rationally designed and produced by advanced spray-drying particle engineering from an organic solution in closed mode (no water) from dilute solution. Scanning electron microscopy indicated that these particles had both optimal particle morphology and surface morphology, and the particle size distributions were suitable for pulmonary delivery. Comprehensive and systematic physicochemical characterization and in vitro aerosol dispersion performance revealed significant differences between these two fluoroquinolone antibiotics following spray drying as drug aerosols and as cospray-dried antibiotic drug: DPPC aerosols. Fourier transform infrared spectroscopy and confocal Raman microspectroscopy were employed to probe composition and interactions in the solid state. Spray-dried MOXI was rendered noncrystalline (amorphous) following organic solution advanced spray drying. This was in contrast to spray-dried OFLX, which retained partial crystallinity, as did OFLX:DPPC powders at certain compositions. Aerosol dispersion performance was conducted using inertial impaction with a dry powder inhaler device approved for human use. The present study demonstrates that the use of DPPC offers improved aerosol delivery of MOXI as cospray-dried microparticulate/nanoparticulate powders, whereas residual partial crystallinity influenced aerosol dispersion of OFLX and most of the compositions of OFLX:DPPC inhalation powders. PMID:24092972

A pilot study on understanding the journey of advanced prostate cancer patients.

PubMed

Wagholikar, Amol; Fung, Maggie; Nelson, Colleen

2011-01-01

patient's clinical records (41%) followed by Urologist (14%) and other clinicians (14%). The data analysis also showed that selenium was the common complementary supplement (55%) used by the patients and about 48% patients did not use any OTC drugs. The most common OTC used by the patients was Paracetamol (about 45%). The results have provided a foundation to the architecture of the proposed technology solution. The outcomes of this study are incorporated in design of the proposed patient journey browser system. A basic version of the system is currently being used at the advanced prostate cancer MDT meetings.

Pharmacokinetics of total thyroxine after repeated oral administration of levothyroxine solution and its clinical efficacy in hypothyroid dogs.

PubMed

van Dijl, I C; Le Traon, G; van de Meulengraaf, B D A M; Burgaud, S; Horspool, L J I; Kooistra, H S

2014-01-01

Oral levothyroxine (l-T4 ) supplementation is commonly used to treat hypothyroid dogs. Investigate the plasma profile and pharmacokinetics of total thyroxine (tT4 ) after PO administration of a l-T4 solution and its clinical efficacy in hypothyroid dogs. Ten dogs with naturally occurring hypothyroidism. After hypothyroidism diagnosis and supplementation with l-T4 solution PO q24h at 20 μg/kg BW for minimum 4 weeks, the plasma profile and pharmacokinetics of tT4 were determined over 34 hours and the clinical condition of the dogs was evaluated. Before dosing for pharmacokinetic evaluation, mean tT4 concentration was 23 ± 9 nmol/L. l-T4 was absorbed rapidly (tmax , 5 hours), reaching a mean maximal tT4 concentration of 56 ± 11 nmol/L. The apparent terminal half-life was 11.8 hours. Clinical signs of hypothyroidism improved or resolved in all dogs after 4 weeks of treatment. The dosage of 20 μg/kg PO q24h was judged appropriate in 5 dogs, and 4 dogs required slight increases (9-16%). Twice daily treatment, with a 30% increase in dosage, was necessary for 1 dog. The pharmacokinetics of l-T4 in hypothyroid dogs was similar to that reported in healthy euthyroid dogs. Clinical and hormonal responses to l-T4 solution were rapid in all dogs. The starting dosage of 20 μg/kg PO q24h was suitable for maintenance supplementation in 50% of the dogs, minor dosage modification was required in 4 other dogs, and treatment q12h was required in 1 dog. Copyright © 2014 by the American College of Veterinary Internal Medicine.

Conference report: Clinical and Pharmaceutical Solutions through analysis (CPSA USA 2013): connecting patients and subject numbers through analysis.

PubMed

Needham, Shane; Premkumar, Noel; Weng, Naidong; Lee, Mike

2014-02-01

The 16th Annual Symposium on Clinical and Pharmaceutical Solutions through Analysis (CPSA) 7-10 October 2013, Sheraton Bucks County Hotel, Langhorne, PA, USA. The 2013 CPSA brought together the various US FDA regulated analytical fields affecting a 'patient' for the first time - bioanalysts supporting IND and NDAs, clinical diagnostic and pathology laboratory personnel, and clinical researchers that provide insights into new biomarkers. Although the regulatory requirements are different for each of the above disciplines, the unique analytical perspectives that affect the patient were shared - and the goal of the 2013 CPSA - 'Connecting Patients and Subject Numbers Through Analysis' was achieved.

Home inotropic therapy in advanced heart failure: cost analysis and clinical outcomes.

PubMed

Harjai, K J; Mehra, M R; Ventura, H O; Lapeyre, Y M; Murgo, J P; Stapleton, D D; Smart, F W

1997-11-05

This study was conducted to assess cost savings and clinical outcomes associated with the use of home i.v. inotropic therapy in patients with advanced (New York Heart Association [NYHA] class IV) heart failure. Retrospective analysis. Tertiary care referral center. Twenty-four patients (13 men, 11 women; age, 61+/-12 years) with left ventricular ejection fraction <30% and heart failure refractory to oral agents required home i.v. inotropic therapy for at least 4 consecutive weeks between May 1994 and April 1996. Inotropic agents used included dobutamine (n=20; dose, 5.0+/-2.2 microg/kg/min) or milrinone (n=7; dose, 0.53+/-0.05 microg/kg/min). Cost of care and clinical outcomes (hospital admissions, length of hospital stay, NYHA functional class) were compared during the period of inotropic therapy (study period) and the immediate preceding period of equal duration (control period). In comparison to the control period, the study period (3.9+/-2.7 months) was associated with a 16% reduction in cost, amounting to a calculated savings of $5,700 per patient or $1,465 per patient per month. Concomitantly, a decrease in the number of hospital admissions from 2.7+/-2.6 to 1.3+/-1.3 (p=0.056) and length of hospital stay from 20.9+/-12.7 to 5.5+/-5.4 days (p=0.0004) was observed with improvement in NYHA functional class from 4.0+/-0.0 to 2.7+/-0.9 (p<0.0001). Eight patients (38%) died after 2.8+/-1.7 months of home i.v. inotropic therapy. Home i.v. inotropic therapy reduces hospital admissions, length of stay, and cost of care and improves functional class in patients with advanced (NYHA class IV) heart failure.

Generalist solutions to overprescribing: a joint challenge for clinical and academic primary care.

PubMed

Reeve, Joanne; Bancroft, Rebecca

2014-01-01

Polypharmacy is a phenomenon of modern health care that can offer benefits in terms of patient outcomes. Known risks associated with so-called inappropriate polypharmacy can be reduced through good medicine management and appropriate use of clinical guidelines. However, we now see a growing literature highlighting additional risks to individual well-being and social functioning not recognised within these existing frameworks - the burden of polypharmacy and a problem of overprescribing. We need a new approach to defining and understanding inappropriate polypharmacy from a person-centred perspective. This paper discusses practice-based work exploring the impact of introducing generalist needs assessment for elderly patients with multiple chronic morbidities. The work suggests that generalist care offers something 'different' to current chronic disease management models, but highlights the need for formal evaluation to determine whether it is 'better'. We call for new collaborative research between clinical and academic partners to address the question as to whether generalist care offers solutions to the problems of the burden of polypharmacy.

Intestinal obstruction management in patients with advanced abdominal neoplasia.

PubMed

Simion, L; Straja, Nd; Alecu, M; Poroch, V; Moşoiu, D; Panti, C; Grigorean, V; Brătucu, E

2014-01-01

The present study describes the difficulties encountered in the diagnostic process and treatment of intestinal obstruction developed by patients with advanced abdominal neoplasia. This unicentric and retrospective study evaluates patients suffering from intestinal occlusion operated on at the First Surgical Clinic of the Oncology Institute in Bucharest, over a period of 4 years (2010 - 2013). Of these, 61 cases in which the occlusion occurred on the background of an advanced abdominal neoplasia were selected. We considered as advanced those cases of abdominal cancer where curative oncologic treatment is no longer possible due to the evolution stage. The random selection of the study period, the introduction of all the patients identified with this type of pathology, as well as the concentration of advanced abdominal neoplasia at the Oncology Institute in Bucharest are the elements that allow us to state that the results of this study are representative. Particularities related to the clinical aspects of the intestinal occlusion in these patients, as well as difficulties in establishing the correct diagnosis were encountered.Surgical cure of the occlusion, with palliative aim of course,was possible in only 47 cases (representing 77.05%). A standard treatment course cannot be devised for this type of patients. Palliative care, indispensable in cases of advanced neoplastic disease, remains the sole therapeutic method available for patients with no surgical cure for the obstruction. The main objective, for the entire study lot, was to ensure an as high as possible quality of life,a factor we must bear in mind as often as possible when choosing a surgical solution. Of course, when surgical treatment can be applied, overcoming the occlusive episode prolongs these patients' life and can even allow for other courses of complementary treatment to be undertaken. Celsius.

Using case study within a sequential explanatory design to evaluate the impact of specialist and advanced practice roles on clinical outcomes: the SCAPE study.

PubMed

Lalor, Joan G; Casey, Dympna; Elliott, Naomi; Coyne, Imelda; Comiskey, Catherine; Higgins, Agnes; Murphy, Kathy; Devane, Declan; Begley, Cecily

2013-04-08

The role of the clinical nurse/midwife specialist and advanced nurse/midwife practitioner is complex not least because of the diversity in how the roles are operationalised across health settings and within multidisciplinary teams. This aim of this paper is to use The SCAPE Study: Specialist Clinical and Advanced Practitioner Evaluation in Ireland to illustrate how case study was used to strengthen a Sequential Explanatory Design. In Phase 1, clinicians identified indicators of specialist and advanced practice which were then used to guide the instrumental case study design which formed the second phase of the larger study. Phase 2 used matched case studies to evaluate the effectiveness of specialist and advanced practitioners on clinical outcomes for service users. Data were collected through observation, documentary analysis, and interviews. Observations were made of 23 Clinical Specialists or Advanced Practitioners, and 23 matched clinicians in similar matched non-postholding sites, while they delivered care. Forty-one service users, 41 clinicians, and 23 Directors of Nursing or Midwifery were interviewed, and 279 service users completed a survey based on the components of CS and AP practice identified in Phase 1. A coding framework, and the generation of cross tabulation matrices in NVivo, was used to make explicit how the outcome measures were confirmed and validated from multiple sources. This strengthened the potential to examine single cases that seemed 'different', and allowed for cases to be redefined. Phase 3 involved interviews with policy-makers to set the findings in context. Case study is a powerful research strategy to use within sequential explanatory mixed method designs, and adds completeness to the exploration of complex issues in clinical practice. The design is flexible, allowing the use of multiple data collection methods from both qualitative and quantitative paradigms. Multiple approaches to data collection are needed to evaluate the impact

Constructing an Ethical Training for Advanced Nursing Practice: An Interactionist and Competency-Based Approach.

PubMed

Pariseau-Legault, Pierre; Lallier, Melisa

2016-07-01

Advanced practice nurses are working in a highly interdisciplinary and political context. Such situations can influence the deliberative and ethical decision-making processes in which they are also involved. This can subsequently compromise their abilities to protect their moral integrity, to find innovative and nondualistic solutions to complex ethical problems, and to collaborate with other health professionals. The authors constructed a training program inspired by discourse and narrative ethics. The objective pursued was to develop advanced practice nurses' moral integrity, highlight the ethical component of their clinical judgement, and foster the development of their deliberative competencies. The pedagogical process proposed exposes how an ethical curriculum adapted to the context in which advanced practice nurses evolve can address power relationships inherent in ethical decision making. The authors suggest that this pedagogical approach has the potential to optimize the consolidation of ethical, reflective, and deliberative competencies among advanced practice nurses. [J Nurs Educ. 2016;55(7):399-402.]. Copyright 2016, SLACK Incorporated.

Design of clinical trials for therapeutic cancer vaccines development.

PubMed

Mackiewicz, Jacek; Mackiewicz, Andrzej

2009-12-25

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

Gastroenterology in developing countries: Issues and advances

PubMed Central

Mandeville, Kate L; Krabshuis, Justus; Ladep, Nimzing Gwamzhi; Mulder, Chris JJ; Quigley, Eamonn MM; Khan, Shahid A

2009-01-01

Developing countries shoulder a considerable burden of gastroenterological disease. Infectious diseases in particular cause enormous morbidity and mortality. Diseases which afflict both western and developing countries are often seen in more florid forms in poorer countries. Innovative techniques continuously improve and update gastroenterological practice. However, advances in diagnosis and treatment which are commonplace in the West, have yet to reach many developing countries. Clinical guidelines, based on these advances and collated in resource-rich environments, lose their relevance outside these settings. In this two-part review, we first highlight the global burden of gastroenterological disease in three major areas: diarrhoeal diseases, hepatitis B, and Helicobacter pylori. Recent progress in their management is explored, with consideration of future solutions. The second part of the review focuses on the delivery of clinical services in developing countries. Inadequate numbers of healthcare workers hamper efforts to combat gastroenterological disease. Reasons for this shortage are examined, along with possibilities for increased specialist training. Endoscopy services, the mainstay of gastroenterology in the West, are in their infancy in many developing countries. The challenges faced by those setting up a service are illustrated by the example of a Nigerian endoscopy unit. Finally, we highlight the limited scope of many clinical guidelines produced in western countries. Guidelines which take account of resource limitations in the form of “cascades” are advocated in order to make these guidelines truly global. Recognition of the different working conditions facing practitioners worldwide is an important step towards narrowing the gap between gastroenterology in rich and poor countries. PMID:19533805

Advancing the Scientific Foundation for Evidence-Based Practice in Clinical Child and Adolescent Psychology.

PubMed

Roberts, Michael C; Blossom, Jennifer B; Evans, Spencer C; Amaro, Christina M; Kanine, Rebecca M

2017-01-01

Evidence-based practice (EBP) has become a central focus in clinical child and adolescent psychology. As originally defined, EBP in psychology is the integration of the best available research evidence, patient characteristics, and clinical expertise. Although evidence-based perspectives have garnered widespread acceptance in recent years, there has also been some confusion and disagreement about the 3-part definition of EBP, particularly the role of research. In this article, we first provide a brief review of the development of EBP in clinical child and adolescent psychology. Next, we outline the following 4 points to help clarify the understanding of EBP: (a) knowledge should not be confused with epistemic processes, (b) research on clinician and client factors is needed for EBP, (c) research on assessment is needed for EBP, and (d) the 3-part conceptualization of EBP can serve as a useful framework to guide research. Based on these principles, we put forth a slightly revised conceptualization of EBP, in which the role of research is expanded and more clearly operationalized. Finally, based on our review of the literature, we offer illustrative examples of specific directions for future research to advance the evidence base for EBP in clinical child and adolescent psychology.

Quantitative imaging biomarkers: the application of advanced image processing and analysis to clinical and preclinical decision making.

PubMed

Prescott, Jeffrey William

2013-02-01

The importance of medical imaging for clinical decision making has been steadily increasing over the last four decades. Recently, there has also been an emphasis on medical imaging for preclinical decision making, i.e., for use in pharamaceutical and medical device development. There is also a drive towards quantification of imaging findings by using quantitative imaging biomarkers, which can improve sensitivity, specificity, accuracy and reproducibility of imaged characteristics used for diagnostic and therapeutic decisions. An important component of the discovery, characterization, validation and application of quantitative imaging biomarkers is the extraction of information and meaning from images through image processing and subsequent analysis. However, many advanced image processing and analysis methods are not applied directly to questions of clinical interest, i.e., for diagnostic and therapeutic decision making, which is a consideration that should be closely linked to the development of such algorithms. This article is meant to address these concerns. First, quantitative imaging biomarkers are introduced by providing definitions and concepts. Then, potential applications of advanced image processing and analysis to areas of quantitative imaging biomarker research are described; specifically, research into osteoarthritis (OA), Alzheimer's disease (AD) and cancer is presented. Then, challenges in quantitative imaging biomarker research are discussed. Finally, a conceptual framework for integrating clinical and preclinical considerations into the development of quantitative imaging biomarkers and their computer-assisted methods of extraction is presented.

Visual disturbances in advanced cancer patients: clinical observations.

PubMed

Saita, L; Polastri, D; De Conno, F

1999-03-01

Visual disturbances in advanced cancer patients are very rarely signaled, evaluated, or adequately treated. The main causes of sight disturbances are primary eye tumors, ocular metastases, and some paraneoplastic syndromes. Sight alteration can also be associated with asthenia, fatigue, anemia, and hypovitaminosis. These symptoms can be monocular or binocular, and their gravity and evolution can vary. Based on a survey of 156 patients, we estimate the prevalence of visual disturbances to be 12% in advanced cancer patients.

Recent Advances in Paper-Based Sensors

PubMed Central

Liana, Devi D.; Raguse, Burkhard; Gooding, J. Justin; Chow, Edith

2012-01-01

Paper-based sensors are a new alternative technology for fabricating simple, low-cost, portable and disposable analytical devices for many application areas including clinical diagnosis, food quality control and environmental monitoring. The unique properties of paper which allow passive liquid transport and compatibility with chemicals/biochemicals are the main advantages of using paper as a sensing platform. Depending on the main goal to be achieved in paper-based sensors, the fabrication methods and the analysis techniques can be tuned to fulfill the needs of the end-user. Current paper-based sensors are focused on microfluidic delivery of solution to the detection site whereas more advanced designs involve complex 3-D geometries based on the same microfluidic principles. Although paper-based sensors are very promising, they still suffer from certain limitations such as accuracy and sensitivity. However, it is anticipated that in the future, with advances in fabrication and analytical techniques, that there will be more new and innovative developments in paper-based sensors. These sensors could better meet the current objectives of a viable low-cost and portable device in addition to offering high sensitivity and selectivity, and multiple analyte discrimination. This paper is a review of recent advances in paper-based sensors and covers the following topics: existing fabrication techniques, analytical methods and application areas. Finally, the present challenges and future outlooks are discussed. PMID:23112667

Clinical Application of a Hybrid RapidArc Radiotherapy Technique for Locally Advanced Lung Cancer.

PubMed

Silva, Scott R; Surucu, Murat; Steber, Jennifer; Harkenrider, Matthew M; Choi, Mehee

2017-04-01

Radiation treatment planning for locally advanced lung cancer can be technically challenging, as delivery of ≥60 Gy to large volumes with concurrent chemotherapy is often associated with significant risk of normal tissue toxicity. We clinically implemented a novel hybrid RapidArc technique in patients with lung cancer and compared these plans with 3-dimensional conformal radiotherapy and RapidArc-only plans. Hybrid RapidArc was used to treat 11 patients with locally advanced lung cancer having bulky mediastinal adenopathy. All 11 patients received concurrent chemotherapy. All underwent a 4-dimensional computed tomography planning scan. Hybrid RapidArc plans concurrently combined static (60%) and RapidArc (40%) beams. All cases were replanned using 3- to 5-field 3-dimensional conformal radiotherapy and RapidArc technique as controls. Significant reductions in dose were observed in hybrid RapidArc plans compared to 3-dimensional conformal radiotherapy plans for total lung V20 and mean (-2% and -0.6 Gy); contralateral lung mean (-2.92 Gy); and esophagus V60 and mean (-16.0% and -2.2 Gy; all P < .05). Contralateral lung doses were significantly lower for hybrid RapidArc plans compared to RapidArc-only plans (all P < .05). Compared to 3-dimensional conformal radiotherapy, heart V60 and mean dose were significantly improved with hybrid RapidArc (3% vs 5%, P = .04 and 16.32 Gy vs 16.65 Gy, P = .03). However, heart V40 and V45 and maximum spinal cord dose were significantly lower with RapidArc plans compared to hybrid RapidArc plans. Conformity and homogeneity were significantly better with hybrid RapidArc plans compared to 3-dimensional conformal radiotherapy plans ( P < .05). Treatment was well tolerated, with no grade 3+ toxicities. To our knowledge, this is the first report on the clinical application of hybrid RapidArc in patients with locally advanced lung cancer. Hybrid RapidArc permitted safe delivery of 60 to 66 Gy to large lung tumors with concurrent

[Adequacy of clinical interventions in patients with advanced and complex disease. Proposal of a decision making algorithm].

PubMed

Ameneiros-Lago, E; Carballada-Rico, C; Garrido-Sanjuán, J A; García Martínez, A

2015-01-01

Decision making in the patient with chronic advanced disease is especially complex. Health professionals are obliged to prevent avoidable suffering and not to add any more damage to that of the disease itself. The adequacy of the clinical interventions consists of only offering those diagnostic and therapeutic procedures appropriate to the clinical situation of the patient and to perform only those allowed by the patient or representative. In this article, the use of an algorithm is proposed that should serve to help health professionals in this decision making process. Copyright © 2014 SECA. Published by Elsevier Espana. All rights reserved.

Fluctuating capacity and advance decision-making in Bipolar Affective Disorder - Self-binding directives and self-determination.

PubMed

Gergel, Tania; Owen, Gareth S

2015-01-01

For people with Bipolar Affective Disorder, a self-binding (advance) directive (SBD), by which they commit themselves to treatment during future episodes of mania, even if unwilling, can seem the most rational way to deal with an imperfect predicament. Knowing that mania will almost certainly cause enormous damage to themselves, their preferred solution may well be to allow trusted others to enforce treatment and constraint, traumatic though this may be. No adequate provision exists for drafting a truly effective SBD and efforts to establish such provision are hampered by very valid, but also paralysing ethical, clinical and legal concerns. Effectively, the autonomy and rights of people with bipolar are being 'protected' through being denied an opportunity to protect themselves. From a standpoint firmly rooted in the clinical context and experience of mania, this article argues that an SBD, based on a patient-centred evaluation of capacity to make treatment decisions (DMC-T) and grounded within the clinician-patient relationship, could represent a legitimate and ethically coherent form of self-determination. After setting out background information on fluctuating capacity, mania and advance directives, this article proposes a framework for constructing such an SBD, and considers common objections, possible solutions and suggestions for future research. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Clinical practice: new challenges for the advanced practice nurse.

PubMed

Bartel, J C; Buturusis, B

2000-12-01

This report describes the challenges for advanced practice nurses (APNs) relative to supply and demand issues. The article also includes opportunities with the Balanced Budget Act, physician acceptance of Advanced Practice Nurses, and expanding practice opportunities. The challenges include the nursing shortage (both in nursing students and faculty), the aging of the nursing workforce, and a lag in nursing salaries; increased demand for nursing based on aging baby boomers, increasing patient acuity and technology, and new arenas for practice. The Balanced Budget Act of 1997 provided new opportunities for advanced practice nurses, including enhanced autonomy to provide services and bill independently of physicians. With these changes come new opportunities for advanced practice nurse entrepreneurs in the areas of independent practice, including opportunities to positively impact the health of families and communities in alignment with the Federal government's vision for "Healthy People 2010." As physician acceptance of advanced practice nurses continues to grow and in light of the changes in medical practice and education (residency reduction), opportunities to expand collaborative practice arrangements also exist. APNs are best suited to make the most of these changes. One example of an opportunity for independent practice, a Community Wellness Center, is developed as an entrepreneurial venture benefiting both the APN and the health of a community. Who better than registered nurses (RNs), especially those practicing at the advanced level, can ensure that these opportunities and challenges are addressed in an ethical manner and focused on the needs and health of the community?

Advance Directives in Hospice Healthcare Providers: A Clinical Challenge.

PubMed

Luck, George R; Eggenberger, Terry; Newman, David; Cortizo, Jacqueline; Blankenship, Derek C; Hennekens, Charles H

2017-11-01

On a daily basis, healthcare providers, especially those dealing with terminally ill patients, such as hospice workers, witness how advance directives help ensure the wishes of patients. They also witness the deleterious consequences when patients fail to document the care they desire at their end of life. To the best of our knowledge there are no data concerning the prevalence of advance directives among hospice healthcare providers. We therefore explored the prevalence and factors influencing completion rates in a survey of hospice healthcare providers. Surveys that included 32 items to explore completion rates, as well as barriers, knowledge, and demographics, were e-mailed to 2097 healthcare providers, including employees and volunteers, at a nonprofit hospice. Of 890 respondents, 44% reported having completed an advance directive. Ethnicity, age, relationship status, and perceived knowledge were all significant factors influencing the completion rates, whereas years of experience or working directly with patients had no effect. Procrastination, fear of the subject, and costs were common reasons reported as barriers. Upon completion of the survey, 43% said they will now complete an advance directive, and 45% will talk to patients and families about their wishes. The majority of hospice healthcare providers have not completed an advance directive. These results are very similar to those for other healthcare providers treating patients with terminal diseases, specifically oncologists. Because, at completion, 43% said that they would now complete an advance directive, such a survey of healthcare providers may help increase completion rates. Copyright © 2017 Elsevier Inc. All rights reserved.

Clean Energy Solutions Center Services (Arabic Translation) (Fact Sheet)

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

Not Available

2014-06-01

This is the Arabic translation of the Clean Energy Solutions Center Services fact sheet. The Clean Energy Solutions Center (Solutions Center) helps governments, advisors and analysts create policies and programs that advance the deployment of clean energy technologies. The Solutions Center partners with international organizations to provide online training, expert assistance, and technical resources on clean energy policy.

Clean Energy Solutions Center Services (Vietnamese Translation) (Fact Sheet)

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

Not Available

2014-11-01

This is the Vietnamese language translation of the Clean Energy Solutions Center (Solutions Center) fact sheet. The Solutions Center helps governments, advisors and analysts create policies and programs that advance the deployment of clean energy technologies. The Solutions Center partners with international organizations to provide online training, expert assistance, and technical resources on clean energy policy.

Clean Energy Solutions Center Services (Chinese Translation) (Fact Sheet)

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

Not Available

2014-04-01

This is the Chinese language translation of the Clean Energy Solutions Center (Solutions Center) fact sheet. The Solutions Center helps governments, advisors and analysts create policies and programs that advance the deployment of clean energy technologies. The Solutions Center partners with international organizations to provide online training, expert assistance, and technical resources on clean energy policy.

Advancing beyond the system: telemedicine nurses' clinical reasoning using a computerised decision support system for patients with COPD - an ethnographic study.

PubMed

Barken, Tina Lien; Thygesen, Elin; Söderhamn, Ulrika

2017-12-28

Telemedicine is changing traditional nursing care, and entails nurses performing advanced and complex care within a new clinical environment, and monitoring patients at a distance. Telemedicine practice requires complex disease management, advocating that the nurses' reasoning and decision-making processes are supported. Computerised decision support systems are being used increasingly to assist reasoning and decision-making in different situations. However, little research has focused on the clinical reasoning of nurses using a computerised decision support system in a telemedicine setting. Therefore, the objective of the study is to explore the process of telemedicine nurses' clinical reasoning when using a computerised decision support system for the management of patients with chronic obstructive pulmonary disease. The factors influencing the reasoning and decision-making processes were investigated. In this ethnographic study, a combination of data collection methods, including participatory observations, the think-aloud technique, and a focus group interview was employed. Collected data were analysed using qualitative content analysis. When telemedicine nurses used a computerised decision support system for the management of patients with complex, unstable chronic obstructive pulmonary disease, two categories emerged: "the process of telemedicine nurses' reasoning to assess health change" and "the influence of the telemedicine setting on nurses' reasoning and decision-making processes". An overall theme, termed "advancing beyond the system", represented the connection between the reasoning processes and the telemedicine work and setting, where being familiar with the patient functioned as a foundation for the nurses' clinical reasoning process. In the telemedicine setting, when supported by a computerised decision support system, nurses' reasoning was enabled by the continuous flow of digital clinical data, regular video-mediated contact and shared decision

Degree of corneal anaesthesia after topical application of 0.4% oxybuprocaine hydrochloride and 0.5% proparacaine hydrochloride ophthalmic solution in clinically normal cattle.

PubMed

Little, W B; Jean, G St; Sithole, F; Little, E; Jean, K Yvorchuk-St

2016-06-01

The use of corneal anaesthesia is necessary for a range of clinical purposes. Therefore, we assessed and compared the efficacy of corneal anaesthesia after application of 0.4% oxybuprocaine hydrochloride and 0.5% proparacaine hydrochloride ophthalmic solution in clinically normal cattle. The 24 clinically normal cows were allocated into two groups. Cows in group 1 (n = 12) received 0.2 mL of 0.4% oxybuprocaine hydrochloride with fluorescein ophthalmic solution in one eye and 0.2 mL of sterile saline (0.9% NaCl) with fluorescein in the contralateral eye (control). Group 2 (n = 12) received 0.2 mL of 0.4% oxybuprocaine hydrochloride with fluorescein ophthalmic solution in one eye and 0.2 mL of 0.5% proparacaine hydrochloride with fluorescein in the contralateral eye (control). In each group, corneal touch threshold was determined by Cochet-Bonnet aesthesiometer for both eyes immediately prior to topical administration of solutions, at 1 min and 5 min after administration of topical solutions and every 5 min thereafter for a total of 75 min. Significant corneal anaesthesia was noted immediately following topical application of both oxybuprocaine and proparacaine as compared with controls, with maximal corneal anaesthesia noted 1 min after administration. Both oxybuprocaine and proparacaine produced significant corneal anaesthesia for the duration of the 75-min study. Neither oxybuprocaine hydrochloride nor proparacaine hydrochloride treatment resulted in visible adverse effects. There are limited data available demonstrating the efficacy and duration of corneal anaesthetic agents in cattle. Both oxybuprocaine hydrochloride and proparacaine hydrochloride should be considered practical options for providing corneal anaesthesia in cattle in a clinical setting. © 2016 Australian Veterinary Association.

Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried cyclosporine A multifunctional particles for dry powder inhalation aerosol delivery

PubMed Central

Wu, Xiao; Zhang, Weifen; Hayes, Don; Mansour, Heidi M

2013-01-01

In this systematic and comprehensive study, inhalation powders of the polypeptide immunosuppressant drug – cyclosporine A – for lung delivery as dry powder inhalers (DPIs) were successfully designed, developed, and optimized. Several spray drying pump rates were rationally chosen. Comprehensive physicochemical characterization and imaging was carried out using scanning electron microscopy, hot-stage microscopy, differential scanning calorimetry, powder X-ray diffraction, Karl Fischer titration, laser size diffraction, and gravimetric vapor sorption. Aerosol dispersion performance was conducted using a next generation impactor with a Food and Drug Administration-approved DPI device. These DPIs displayed excellent aerosol dispersion performance with high values in emitted dose, respirable fraction, and fine particle fraction. In addition, novel multifunctional inhalation aerosol powder formulations of cyclosporine A with lung surfactant-mimic phospholipids were also successfully designed and developed by advanced organic solution cospray drying in closed mode. The lung surfactantmimic phospholipids were 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-snglycero- 3-(phosphor-rac-1-glycerol). These cyclosporine A lung surfactant-mimic aerosol powder formulations were comprehensively characterized. Powder X-ray diffraction and differential scanning calorimetry confirmed that the phospholipid bilayer structure in the solid state was preserved following advanced organic solution spray drying in closed mode. These novel multifunctional inhalation powders were optimized for DPI delivery with excellent aerosol dispersion performance and high aerosol performance parameters. PMID:23569375

Advanced musculoskeletal physiotherapists in post arthroplasty review clinics: a state wide implementation program evaluation.

PubMed

Harding, Paula; Burge, Angela; Walter, Kerrie; Shaw, Bridget; Page, Carolyn; Phan, Uyen; Terrill, Desiree; Liew, Susan

2018-03-01

To evaluate outcomes following a state-wide implementation of post arthroplasty review (PAR) clinics for patients following total hip and knee arthroplasty, led by advanced musculoskeletal physiotherapists in collaboration with orthopaedic specialists. A prospective observational study analysed data collected by 10 implementation sites (five metropolitan and five regional/rural centres) between September 2014 and June 2015. The Victorian Innovation and Reform Impact Assessment Framework was used to assess efficiency, effectiveness (access to care, safety and quality, workforce capacity, utilisation of skill sets, patient and workforce satisfaction) and sustainability (stakeholder engagement, succession planning and availability of ongoing funding). 2362 planned occasions of service (OOS) were provided for 2057 patients. Reduced patient wait times from referral to appointment were recorded and no adverse events occurred. Average cost savings across 10 sites was AUD$38 per OOS (Baseline $63, PAR clinic $35), representing a reduced pathway cost of 44%. Average annual predicted total value of increased orthopaedic specialist capacity was $11,950 per PAR clinic (range $6149 to $23,400). The Australian Orthopaedic Association review guidelines were met (8/10 sites, 80%) and patient-reported outcome measures were introduced as routine clinical care. High workforce and patient satisfaction were expressed. Eighteen physiotherapists were trained creating a sustainable workforce. Eight sites secured ongoing funding. The PAR clinics delivered a safe, cost-efficient model of care that improved patient access and quality of care compared to traditional specialist-led workforce models. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Violation of ethical principles in clinical research. Influences and possible solutions for Latin America.

PubMed

Cornejo Moreno, Borys Alberto; Gómez Arteaga, Gress Marissell

2012-12-16

Even though we are now well into the 21st century and notwithstanding all the abuse to individuals involved in clinical studies that has been documented throughout History, fundamental ethical principles continue to be violated in one way or another. Here are some of the main factors that contribute to the abuse of subjects participating in clinical trials: paternalism, improper use of informed consent, lack of strict ethical supervision, pressure exerted by health institutions to increase the production of scientific material, and the absence of legislation regarding ethics in terms of health care and research. Are researchers ready to respect fundamental ethical principles in light of the ample window of information provided by individual genomes, while defending the rights of the subjects participating in clinical studies as a major priority? As one of the possible solutions to this problem, education regarding fundamental ethical principles is suggested for participants in research studies as an initial method of cognitive training in ethics, together with the promotion of ethical behavior in order to encourage the adoption of reasonable policies in the field of values, attitudes and behavior.

Clinical Decision Support to Efficiently Identify Patients Eligible for Advanced Heart Failure Therapies.

PubMed

Evans, R Scott; Kfoury, Abdallah G; Horne, Benjamin D; Lloyd, James F; Benuzillo, Jose; Rasmusson, Kismet D; Roberts, Colleen; Lappé, Donald L

2017-10-01

Patients who need and receive timely advanced heart failure (HF) therapies have better long-term survival. However, many of these patients are not identified and referred as soon as they should be. A clinical decision support (CDS) application sent secure email notifications to HF patients' providers when they transitioned to advanced disease. Patients identified with CDS in 2015 were compared with control patients from 2013 to 2014. Kaplan-Meier methods and Cox regression were used in this intention-to-treat analysis to compare differences between visits to specialized and survival. Intervention patients were referred to specialized heart facilities significantly more often within 30 days (57% vs 34%; P < .001), 60 days (69% vs 44%; P < .0001), 90 days (73% vs 49%; P < .0001), and 180 days (79% vs 58%; P < .0001). Age and sex did not predict heart facility visits, but renal disease did and patients of nonwhite race were less likely to visit specialized heart facilities. Significantly more intervention patients were found to be alive at 30 (95% vs 92%; P = .036), 60 (95% vs 90%; P = .0013), 90 (94% vs 87%; P = .0002), and 180 days (92% vs 84%; P = .0001). Age, sex, and some comorbid diseases were also predictors of mortality, but race was not. We found that CDS can facilitate the early identification of patients needing advanced HF therapy and that its use was associated with significantly more patients visiting specialized heart facilities and longer survival. Copyright © 2017 Elsevier Inc. All rights reserved.

Advances in Retinal Prosthetic Research: A Systematic Review of Engineering and Clinical Characteristics of Current Prosthetic Initiatives.

PubMed

Cheng, Derrick L; Greenberg, Paul B; Borton, David A

2017-03-01

To date, reviews of retinal prostheses have focused primarily on devices undergoing human trials in the Western Hemisphere and fail to capture significant advances in materials and engineering research in countries such as Japan and Korea, as well as projects in early stages of development. To address these gaps, this systematic review examines worldwide advances in retinal prosthetic research, evaluates engineering characteristics and clinical progress of contemporary device initiatives, and identifies potential directions for future research in the field of retinal prosthetics. A literature search using PubMed, Google Scholar, and IEEExplore was conducted following the PRISMA Guidelines for Systematic Review. Inclusion criteria were peer-reviewed papers demonstrating progress in human or animal trials and papers discussing the prosthetic engineering design. For each initiative, a description of the device, its engineering considerations, and recent clinical results were provided. Ten prosthetic initiatives met our inclusion criteria and were organized by stimulation location. Of these initiatives, four have recently completed human trials, three are undergoing multi- or single-center human trials, and three are undergoing preclinical animal testing. Only the Argus II (FDA 2013, CE 2011) has obtained FDA approval for use in the United States; the Alpha-IMS (CE 2013) has achieved the highest visual acuity using a Landolt-C test to date and is the only device presently undergoing a multicenter clinical trial. Several distinct approaches to retinal stimulation have been successful in eliciting visual precepts in animals and/or humans. However, many clinical needs are still not met and engineering challenges must be addressed before a retinal prosthesis with the capability to fully and safely restore functional vision can be realized.

Clinical Experience in Advanced Practice Nursing: A Canadian Perspective.

ERIC Educational Resources Information Center

Donnelly, Glenn

2003-01-01

The role of advanced practice (AP) nurses must be clearly articulated and defined and not overshadowed by medical functions. Consensus on their educational preparation and explication of the nature of expertise in advanced practice are needed if AP nurses are to realize the full scope of their practice. (Contains 35 references.) (SK)

Interactive 3-D graphics workstations in stereotaxy: clinical requirements, algorithms, and solutions

NASA Astrophysics Data System (ADS)

Ehricke, Hans-Heino; Daiber, Gerhard; Sonntag, Ralf; Strasser, Wolfgang; Lochner, Mathias; Rudi, Lothar S.; Lorenz, Walter J.

1992-09-01

In stereotactic treatment planning the spatial relationships between a variety of objects has to be taken into account in order to avoid destruction of vital brain structures and rupture of vasculature. The visualization of these highly complex relations may be supported by 3-D computer graphics methods. In this context the three-dimensional display of the intracranial vascular tree and additional objects, such as neuroanatomy, pathology, stereotactic devices, or isodose surfaces, is of high clinical value. We report an advanced rendering method for a depth-enhanced maximum intensity projection from magnetic resonance angiography (MRA) and a walk-through approach to the analysis of MRA volume data. Furthermore, various methods for a multiple-object 3-D rendering in stereotaxy are discussed. The development of advanced applications in medical imaging can hardly be successful if image acquisition problems are disregarded. We put particular emphasis on the use of conventional MRI and MRA for stereotactic guidance. The problem of MR distortion is discussed and a novel three- dimensional approach to the quantification and correction of the distortion patterns is presented. Our results suggest that the sole use of MR for stereotactic guidance is highly practical. The true three-dimensionality of the acquired datasets opens up new perspectives to stereotactic treatment planning. For the first time it is possible now to integrate all the necessary information into 3-D scenes, thus enabling an interactive 3-D planning.

The role and functions of Clinical Nurse Consultants, an Australian advanced practice role: a descriptive exploratory cohort study.

PubMed

Baldwin, Richard; Duffield, Christine Margaret; Fry, Margaret; Roche, Michael; Stasa, Helen; Solman, Annette

2013-03-01

The NSW Health Policy Directive (NSW Department of Health, 2000) lists clinical service and consultancy; clinical leadership; research; education; clinical services planning and management as the five domains of practice for nurses appointed as Clinical Nurse Consultants (CNCs), an Australian advanced practice nurse (APN) role. However, there is no clear definition of what is meant by advanced practice in the Australian nursing context. Nowhere is this more evident than in differentiating between the roles of Clinical Nurse Consultants (CNCs) and Nurse Practitioners (NP) in NSW. To date, limited empirical research has been done to characterise or delineate CNC role activity and responsibility. To investigate (i) the nature of CNC roles, activities and responsibilities, (ii) differentiate between CNCs by their work patterns and activities, and (iii) empirically conceptualize and differentiate ways CNCs practice in terms of an APN typology. The study sample was 56 CNCs at one tertiary level public hospital in Australia. A descriptive exploratory cohort study was conducted to explore CNC role characteristics and patterns of activity. Data were triangulated using an online survey, a follow-up survey, and semi-structured interviews. The data were analysed using descriptive statistics to examine differences between CNC work patterns and role activities. The survey data and the individual reports were thematically analysed to investigate for difference across the population of CNCs. Interpretation of survey and interview data led to an analyst-developed CNC typology of four CNC categories based on the work patterns and activities of Sole Practitioner, Clinic Coordinator, Clinical Team Coordinator and Clinical Leader. The typology was based on the themes interprofessional, role focus, clinical focus and setting as these themes distinguished and differentiated CNC roles. The study provides evidence of great diversity and prioritization within CNC roles. The CNC typology

Clinical Activity of Alectinib in Advanced RET-Rearranged Non-Small Cell Lung Cancer.

PubMed

Lin, Jessica J; Kennedy, Elizabeth; Sequist, Lecia V; Brastianos, Priscilla K; Goodwin, Kelly E; Stevens, Sara; Wanat, Alexandra C; Stober, Lisa L; Digumarthy, Subba R; Engelman, Jeffrey A; Shaw, Alice T; Gainor, Justin F

2016-11-01

Chromosomal rearrangements involving rearranged during transfection gene (RET) occur in 1% to 2% of NSCLCs and may confer sensitivity to rearranged during transfection (RET) inhibitors. Alectinib is an anaplastic lymphoma kinase tyrosine kinase inhibitor (TKI) that also has anti-RET activity in vitro. The clinical activity of alectinib in patients with RET-rearranged NSCLC has not yet been reported. We have described four patients with advanced RET-rearranged NSCLC who were treated with alectinib (600 mg twice daily [n = 3] or 900 mg twice daily [n = 1]) as part of single-patient compassionate use protocols or off-label use of the commercially available drug. Four patients with metastatic RET-rearranged NSCLC were identified. Three of the four had received prior RET TKIs, including cabozantinib and experimental RET inhibitors. In total, we observed two (50%) objective radiographic responses after treatment with alectinib (one confirmed and one unconfirmed), with durations of therapy of 6 months and more than 5 months (treatment ongoing), respectively. Notably, one of these two patients had his dose of alectinib escalated to 900 mg twice daily and had clinical improvement in central nervous system metastases. In addition, one patient (25%) experienced a best response of stable disease lasting approximately 6 weeks (the drug discontinued for toxicity). A fourth patient who was RET TKI-naive had primary progression while receiving alectinib. Alectinib demonstrated preliminary antitumor activity in patients with advanced RET-rearranged NSCLC, most of whom had received prior RET inhibitors. Larger prospective studies with longer follow-up are needed to assess the efficacy of alectinib in RET-rearranged NSCLC and other RET-driven malignancies. In parallel, development of more selective, potent RET TKIs is warranted. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Fluctuating capacity and advance decision-making in Bipolar Affective Disorder — Self-binding directives and self-determination

PubMed Central

Gergel, Tania; Owen, Gareth S.

2015-01-01

For people with Bipolar Affective Disorder, a self-binding (advance) directive (SBD), by which they commit themselves to treatment during future episodes of mania, even if unwilling, can seem the most rational way to deal with an imperfect predicament. Knowing that mania will almost certainly cause enormous damage to themselves, their preferred solution may well be to allow trusted others to enforce treatment and constraint, traumatic though this may be. No adequate provision exists for drafting a truly effective SBD and efforts to establish such provision are hampered by very valid, but also paralysing ethical, clinical and legal concerns. Effectively, the autonomy and rights of people with bipolar are being ‘protected’ through being denied an opportunity to protect themselves. From a standpoint firmly rooted in the clinical context and experience of mania, this article argues that an SBD, based on a patient-centred evaluation of capacity to make treatment decisions (DMC-T) and grounded within the clinician–patient relationship, could represent a legitimate and ethically coherent form of self-determination. After setting out background information on fluctuating capacity, mania and advance directives, this article proposes a framework for constructing such an SBD, and considers common objections, possible solutions and suggestions for future research. PMID:25939286

Development of an Aqueous Ophthalmic Solution with an Enhanced-Solubility Enrofloxacin Crystal, and its Clinical Evaluation in Dogs.

PubMed

Miranda-Calderon, Jorge E; Gutierrez, Lilia; Ocampo, Luis; Garcia-Gutierrez, Ponciano; Tapia, Graciela; Sumano, Hector

2018-01-01

The concern about the frequent use of ciprofloxacin in veterinary medicine is linked to increased antimicrobial resistance. The corresponding fluoroquinolone for veterinary use is enrofloxacin. A new solvate form of enrofloxacin, as dihydrate-hydrochloride (enro-C) with higher water solubility than the parent compound, was formulated as an ophthalmic solution (pH 5). A multicentre, longitudinal, non-inferiority clinical study in a non-hospital environment was designed to treat 36 dogs affected by tobramycin-unresponsive conjunctivitis with either the experimental 0.5% enro-C ophthalmic preparation (enro-CG) or a commercial preparation of ciprofloxacin (cipro-G). Other causes of conjunctivitis were ruled out. Pathogens were isolated and minimum inhibitory concentration (MIC) studies of tobramycin were carried out. Three blocks of bacterial resistance were set up, beginning at the established breakpoint i.e., 4 µg/mL; 8 µg/mL and 16 µg/mL. Eighteen dogs were randomly assigned to each block. The enro-CG group was treated with two drops of the referred preparation (10 mg/eye) twice a day for 7 days, and the cipro-G group was treated with four drops of a 0.3% commercially available ciprofloxacin eye-drop preparation (9 mg/eye) twice a day, also for 7 days. Clinical and bacteriological cure rates were evaluated. Enro-C-treated dogs achieved a clinical cure one day earlier than ciprofloxacin-treated dogs, and unlike this latter group, enro-CG achieved bacteriological cure in all cases. No side effects were observed in either group, but dogs treated with enro-C showed no discomfort, allowing easier treatment-compliance. This is the first study reported on the successful formulation of enrofloxacin as an ophthalmic solution. Clinical assessment reveals outstanding clinical efficacy. It is necessary to conduct further research on clinical efficacy and toxicity, with the chronic use of this preparation under different clinical challenges. Copyright© Bentham Science

Identifying opportunities to advance practice at a large academic medical center using the ASHP Ambulatory Care Self-Assessment Tool.

PubMed

Martirosov, Amber Lanae; Michael, Angela; McCarty, Melissa; Bacon, Opal; DiLodovico, John R; Jantz, Arin; Kostoff, Diana; MacDonald, Nancy C; Mikulandric, Nancy; Neme, Klodiana; Sulejmani, Nimisha; Summers, Bryant B

2018-05-29

The use of the ASHP Ambulatory Care Self-Assessment Tool to advance pharmacy practice at 8 ambulatory care clinics of a large academic medical center is described. The ASHP Ambulatory Care Self-Assessment Tool was developed to help ambulatory care pharmacists assess how their current practices align with the ASHP Practice Advancement Initiative. The Henry Ford Hospital Ambulatory Care Advisory Group (ACAG) opted to use the "Practitioner Track" sections of the tool to assess pharmacy practices within each of 8 ambulatory care clinics individually. The responses to self-assessment items were then compiled and discussed by ACAG members. The group identified best practices and ways to implement action items to advance ambulatory care practice throughout the institution. Three recommended action items were common to most clinics: (1) identify and evaluate solutions to deliver financially viable services, (2) develop technology to improve patient care, and (3) optimize the role of pharmacy technicians and support personnel. The ACAG leadership met with pharmacy administrators to discuss how action items that were both feasible and deemed likely to have a medium-to-high impact aligned with departmental goals and used this information to develop an ambulatory care strategic plan. This process informed and enabled initiatives to advance ambulatory care pharmacy practice within the system. The ASHP Ambulatory Care Self-Assessment Tool was useful in identifying opportunities for practice advancement in a large academic medical center. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Contact Lens Solutions and Contact Lens Discomfort: Examining the Correlations Between Solution Components, Keratitis, and Contact Lens Discomfort.

PubMed

Kuc, Christopher J; Lebow, Kenneth A

2018-06-13

This article will examine the current literature, as it relates to contact lens discomfort (CLD) secondary to contact lens solutions. The reader will better understand the characteristics of contact lenses, as they uniquely interact with each type of contact lens solution and also gain a better comprehension of the components of contact lens solution such as preservatives, surfactants, and chelating agents, which may contribute to discomfort. By investigating corneal staining theory and the mechanisms that contribute to its presence, the reader will gain insight into this clinical finding, which relates to selection of contact lens solutions. The FDA standards for testing solutions and how this relates to contact lens keratitis will also be appraised in regards to current ISO recommendations. Finally, better selection of multipurpose contact lens solution (MPS) and hydrogen peroxide-based solutions for patients should be accessible to the clinician based on this review and preexisting clinical findings or diagnoses. A review of current published literature from peer reviewed journals and online journals was conducted to gain an understanding of contact lens solution's impact on contact lens discomfort. Many studies have been conducted comparing comfort between various types of contact lens solutions. It is challenging to decipher this information and apply it clinically when selecting solutions for patients. By comparing solution components, how contact lens solutions interact with different types of lenses, keratitis related to contact lenses, and preexisting ocular conditions, this review will improve a clinician's ability to eliminate CLD.

Leadership capabilities of physiotherapy leaders in Ireland: Part 2. Clinical specialists and advanced physiotherapy practitioners.

PubMed

McGowan, E; Elliott, N; Stokes, E

2018-05-07

Investigation of the leadership capabilities of physiotherapy managers found that they report predominantly demonstrating capabilities associated with the human resource and structural frames. However, little is known about the leadership capabilities of clinical specialists and advanced physiotherapy practitioners (APPs) who also are identified as having responsibility for leadership. To explore clinical specialists´ and APPs' perceptions of their leadership capabilities and compare them with the reported leadership capabilities of physiotherapy managers. Semi-structured interviews were conducted with a purposive sample of 17 physiotherapy clinical specialists and APPs from a range of practice settings across Ireland. The interviews were analyzed using template analysis and the coding template was based on the Bolman and Deal Leadership framework. The participants described demonstrating leadership capabilities associated with each of the four leadership frames. However, the language used by the clinical specialists/APPs suggested that they work predominantly through the human resource frame. Structural frame capabilities were reported by the clinical specialists/APPs and there were some differences to those reported by the managers. In keeping with the reported leadership capabilities of the physiotherapy managers, the employment of capabilities associated with the political frame varied between participants and symbolic frame capabilities were underused. There are many similarities in the self-reported leadership capabilities of managers and clinical specialists/APPs. However, differences were also noted. Both cohorts of physiotherapy leaders may benefit from specific development programs to develop leadership capabilities associated with the political and symbolic frames.

Advanced pancreatic cancer: a meta-analysis of clinical trials over thirty years

PubMed Central

Hall, Bradley R.; Cannon, Andrew; Atri, Pranita; Wichman, Christopher S.; Smith, Lynette M.; Ganti, Apar K.; Are, Chandrakanth; Sasson, Aaron R.; Kumar, Sushil; Batra, Surinder K.

2018-01-01

Background In contrast to other cancers, survival rates for pancreatic ductal adenocarcinoma (PDAC) patients have improved but minimally over the past thirty years. The aim of this study was to perform a meta-analysis of clinical trials published since 1986 to determine trends in median overall survival in primarily metastatic PDAC. Materials and methods All Phase 2–4 clinical trials published during or after 1986 investigating first-line systemic chemotherapy in metastatic PDAC were included in the meta-analysis. Publications obtained through PubMed and www.ClinicalTrials.gov were cross-referenced to identify additional trials. Trials enrolling fewer than 50% of study participants with metastatic disease were excluded. Results Of 19,488 patients enrolled in 151 clinical trials, 84% had metastatic disease and 16% had locally advanced pancreatic cancer. In clinical trials published from 1986 to 2016, the weighted median overall survival (wMOS) increased by 3.0 months. The median wMOS was higher in combination therapy (7.31 months, IQR 5.4 to 8.5) compared to non-gemcitabine, single-agent therapy (4.76 months, IQR 3.5 to 6.0), gemcitabine monotherapy (6.48 months, IQR 5.9 to 7.2), and gemcitabine plus single-agent therapy (7.09 months, IQR 6.3 to 8.2). Of all regimens used in more than one study arm, FOLFIRINOX had the highest wMOS (10.9 months). Conclusions Regardless of treatment regimen, survival rates in PDAC have minimally improved over time. Of drugs used in two or more study arms, only FOLFIRINOX has a wMOS greater than ten months. Emphasis should, therefore, be placed on identification of novel targets that promote early diagnosis and intervention. Funding The authors on this manuscript are in parts, supported by grants from the National Institutes of Health (EDRN U01 CA200466, SPORE P50 CA127297, R01 CA183459, R21 AA026428 and R01 CA 195586). PMID:29721211

Center to Advance Palliative Care palliative care clinical care and customer satisfaction metrics consensus recommendations.

PubMed

Weissman, David E; Morrison, R Sean; Meier, Diane E

2010-02-01

Data collection and analysis are vital for strategic planning, quality improvement, and demonstration of palliative care program impact to hospital administrators, private funders and policymakers. Since 2000, the Center to Advance Palliative Care (CAPC) has provided technical assistance to hospitals, health systems and hospices working to start, sustain, and grow nonhospice palliative care programs. CAPC convened a consensus panel in 2008 to develop recommendations for specific clinical and customer metrics that programs should track. The panel agreed on four key domains of clinical metrics and two domains of customer metrics. Clinical metrics include: daily assessment of physical/psychological/spiritual symptoms by a symptom assessment tool; establishment of patient-centered goals of care; support to patient/family caregivers; and management of transitions across care sites. For customer metrics, consensus was reached on two domains that should be tracked to assess satisfaction: patient/family satisfaction, and referring clinician satisfaction. In an effort to ensure access to reliably high-quality palliative care data throughout the nation, hospital palliative care programs are encouraged to collect and report outcomes for each of the metric domains described here.

Application of next-generation sequencing in clinical oncology to advance personalized treatment of cancer

PubMed Central

Guan, Yan-Fang; Li, Gai-Rui; Wang, Rong-Jiao; Yi, Yu-Ting; Yang, Ling; Jiang, Dan; Zhang, Xiao-Ping; Peng, Yin

2012-01-01

With the development and improvement of new sequencing technology, next-generation sequencing (NGS) has been applied increasingly in cancer genomics research over the past decade. More recently, NGS has been adopted in clinical oncology to advance personalized treatment of cancer. NGS is used to identify novel and rare cancer mutations, detect familial cancer mutation carriers, and provide molecular rationale for appropriate targeted therapy. Compared to traditional sequencing, NGS holds many advantages, such as the ability to fully sequence all types of mutations for a large number of genes (hundreds to thousands) in a single test at a relatively low cost. However, significant challenges, particularly with respect to the requirement for simpler assays, more flexible throughput, shorter turnaround time, and most importantly, easier data analysis and interpretation, will have to be overcome to translate NGS to the bedside of cancer patients. Overall, continuous dedication to apply NGS in clinical oncology practice will enable us to be one step closer to personalized medicine. PMID:22980418

Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer.

PubMed

Strunk, H M; Henseler, J; Rauch, M; Mücke, M; Kukuk, G; Cuhls, H; Radbruch, L; Zhang, L; Schild, H H; Marinova, M

2016-07-01

Evaluation of ultrasound-guided high-intensity focused ultrasound (HIFU) used for the first time in Germany in patients with inoperable pancreatic cancer for reduction of tumor volume and relief of tumor-associated pain. 15 patients with locally advanced inoperable pancreatic cancer and tumor-related pain symptoms were treated by HIFU (n = 6 UICC stage III, n = 9 UICC stage IV). 13 patients underwent simultaneous standard chemotherapy. Ablation was performed using the JC HIFU system (Chongqing, China HAIFU Company) with an ultrasonic device for real-time imaging. Imaging follow-up (US, CT, MRI) and clinical assessment using validated questionnaires (NRS, BPI) was performed before and up to 15 months after HIFU. Despite biliary or duodenal stents (4/15) and encasement of visceral vessels (15/15), HIFU treatment was performed successfully in all patients. Treatment time and sonication time were 111 min and 1103 s, respectively. The applied total energy was 386 768 J. After HIFU ablation, contrast-enhanced imaging showed devascularization of treated tumor regions with a significant average volume reduction of 63.8 % after 3 months. Considerable pain relief was achieved in 12 patients after HIFU (complete or partial pain reduction in 6 patients). US-guided HIFU with a suitable acoustic pathway can be used for local tumor control and relief of tumor-associated pain in patients with locally advanced pancreatic cancer. • US-guided HIFU allows an additive treatment of unresectable pancreatic cancer.• HIFU can be used for tumor volume reduction.• Using HIFU, a significant reduction of cancer-related pain was achieved.• HIFU provides clinical benefit in patients with pancreatic cancer. Citation Format: • Strunk HM, Henseler J, Rauch M et al. Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer. Fortschr Röntgenstr 2016; 188: 662 - 670. © Georg Thieme Verlag KG

MRI helps depict clinically undetectable risk factors in advanced stage retinoblastomas.

PubMed

Galluzzi, Paolo; Hadjistilianou, Theodora; Cerase, Alfonso; Toti, Paolo; Leonini, Sara; Bracco, Sandra; de Francesco, Sonia; Galimberti, Daniela; Balducci, Donatella; Piu, Pietro; Monti, Lucia; Bellini, Matteo; Caini, Mauro; Rossi, Alessandro

2015-02-01

This study compared high-resolution MRI with histology in advanced stage retinoblastomas in which ophthalmoscopy and ultrasonography did not give an exhaustive depiction of the tumour and/or its extension. MRI of orbits and head in 28 retinoblastoma patients (28 eyes) treated with primary enucleation were evaluated. Iris neoangiogenesis, infiltrations of optic nerve, choroid, anterior segment and sclera suspected at MR and histology were compared. Abnormal anterior segment enhancement (AASE) was also correlated with histologically proven infiltrations. Brain images were also evaluated. Significant values were obtained for: prelaminar optic nerve (ON) sensitivity (0.88), positive predictive value (PPV) (0.75) and negative predictive value (NPV) (0.71); post-laminar ON sensitivity (0.50), specificity (0.83), PPV (0.50) and NPV (0.83); overall choroid sensitivity (0.82), and massive choroid NPV (0.69); scleral specificity (1), and NPV (1). AASE correlated with iris neoangiogenesis in 14 out of 19 eyes, and showed significant values for: overall ON PPV (0.65), prelaminar ON sensitivity (0.65), and PPV (0.61), post-laminar ON NPV (0.64); overall choroid sensitivity (0.77), PPV (0.59) and NPV (0.73); scleral NPV (0.83); anterior segment sensitivity (1), and NPV (1). Odds ratios (OR) and accuracy were significant in scleral and prelaminar optic nerve infiltration. Brain examination was unremarkable in all cases. High-resolution MRI may add important findings to clinical evaluation of advanced stage retinoblastomas. © The Author(s) 2015 Reprints and permissions:]br]sagepub.co.uk/journalsPermissions.nav.

Neonatal physical therapy. Part I: clinical competencies and neonatal intensive care unit clinical training models.

PubMed

Sweeney, Jane K; Heriza, Carolyn B; Blanchard, Yvette

2009-01-01

To describe clinical training models, delineate clinical competencies, and outline a clinical decision-making algorithm for neonatal physical therapy. In these updated practice guidelines, advanced clinical training models, including precepted practicum and residency or fellowship training, are presented to guide practitioners in organizing mentored, competency-based preparation for neonatal care. Clinical competencies in neonatal physical therapy are outlined with advanced clinical proficiencies and knowledge areas specific to each role. An algorithm for decision making on examination, evaluation, intervention, and re-examination processes provides a framework for clinical reasoning. Because of advanced-level competency requirements and the continuous examination, evaluation, and modification of procedures during each patient contact, the intensive care unit is a restricted practice area for physical therapist assistants, physical therapist generalists, and physical therapy students. Accountable, ethical physical therapy for neonates requires advanced, competency-based training with a preceptor in the pediatric subspecialty of neonatology.

Technical solutions for simultaneous MEG and SEEG recordings: towards routine clinical use.

PubMed

Badier, J M; Dubarry, A S; Gavaret, M; Chen, S; Trébuchon, A S; Marquis, P; Régis, J; Bartolomei, F; Bénar, C G; Carron, R

2017-09-21

The simultaneous recording of intracerebral EEG (stereotaxic EEG, SEEG) and magnetoencephalography (MEG) is a promising strategy that provides both local and global views on brain pathological activity. Yet, acquiring simultaneous signals poses difficult technical issues that hamper their use in clinical routine. Our objective was thus to develop a set of solutions for recording a high number of SEEG channels while preserving signal quality. We recorded data in a patient with drug resistant epilepsy during presurgical evaluation. We used dedicated insertion screws and optically insulated amplifiers. We recorded 137 SEEG contacts on 10 depth electrodes (5-15 contacts each) and 248 MEG channels (magnetometers). Signal quality was assessed by comparing the distribution of RMS values in different frequency bands to a reference set of MEG acquisitions. The quality of signals was excellent for both MEG and SEEG; for MEG, it was comparable to that of MEG signals without concurrent SEEG. Discharges involving several structures on SEEG were visible on MEG, whereas discharges limited in space were not seen at the surface. SEEG can now be recorded simultaneously with whole-head MEG in routine. This opens new avenues, both methodologically for understanding signals and improving signal processing methods, and clinically for future combined analyses.

Advanced CD-SEM solution for edge placement error characterization of BEOL pitch 32nm metal layers

NASA Astrophysics Data System (ADS)

Charley, A.; Leray, P.; Lorusso, G.; Sutani, T.; Takemasa, Y.

2018-03-01

Metrology plays an important role in edge placement error (EPE) budgeting. Control for multi-patterning applications as new critical distances needs to be measured (edge to edge) and requirements become tighter and tighter in terms of accuracy and precision. In this paper we focus on imec iN7 BEOL platform and particularly on M2 patterning scheme using SAQP + block EUV for a 7.5 track logic design. Being able to characterize block to SAQP edge misplacement is important in a budgeting exercise (1) but is also extremely difficult due to challenging edge detection with CD-SEM (similar materials, thin layers, short distances, 3D features). In this study we develop an advanced solution to measure block to SAQP placement, we characterize it in terms of sensitivity, precision and accuracy through the comparison to reference metrology. In a second phase, the methodology is applied to budget local effects and the results are compared to the characterization of the SAQP and block independently.

Breastfeeding Solution Circle.

PubMed

Hilton, Sioned

2011-10-01

It is widely accepted and backed by research that breastfeeding is the number one feeding choice for babies, and direct from mothers' breasts is the ideal. However the early days can be challenging. Supporting mothers to succeed with their breastfeeding journey is a rewarding role and being able to advise and guide on overcoming the various hurdles is great. Keeping up to date on the research and advancements in breastfeeding support is vital and a general knowledge of the solutions to help will be of huge benefit to the mothers you are working with. This article examines the problems and some tried and tested solutions.

Early clinical experience utilizing scintillator with optical fiber (SOF) detector in clinical boron neutron capture therapy: its issues and solutions.

PubMed

Ishikawa, Masayori; Yamamoto, Tetsuya; Matsumura, Akira; Hiratsuka, Junichi; Miyatake, Shin-Ichi; Kato, Itsuro; Sakurai, Yoshinori; Kumada, Hiroaki; Shrestha, Shubhechha J; Ono, Koji

2016-08-09

Real-time measurement of thermal neutrons in the tumor region is essential for proper evaluation of the absorbed dose in boron neutron capture therapy (BNCT) treatment. The gold wire activation method has been routinely used to measure the neutron flux distribution in BNCT irradiation, but a real-time measurement using gold wire is not possible. To overcome this issue, the scintillator with optical fiber (SOF) detector has been developed. The purpose of this study is to demonstrate the feasibility of the SOF detector as a real-time thermal neutron monitor in clinical BNCT treatment and also to report issues in the use of SOF detectors in clinical practice and their solutions. Clinical measurements using the SOF detector were carried out in 16 BNCT clinical trial patients from December 2002 until end of 2006 at the Japanese Atomic Energy Agency (JAEA) and Kyoto University Research Reactor Institute (KURRI). The SOF detector worked effectively as a real-time thermal neutron monitor. The neutron fluence obtained by the gold wire activation method was found to differ from that obtained by the SOF detector. The neutron fluence obtained by the SOF detector was in better agreement with the expected fluence than with gold wire activation. The estimation error for the SOF detector was small in comparison to the gold wire measurement. In addition, real-time monitoring suggested that the neutron flux distribution and intensity at the region of interest (ROI) may vary due to the reactor condition, patient motion and dislocation of the SOF detector. Clinical measurements using the SOF detector to measure thermal neutron flux during BNCT confirmed that SOF detectors are effective as a real-time thermal neutron monitor. To minimize the estimation error due to the displacement of the SOF probe during treatment, a loop-type SOF probe was developed.

[Clinical Analysis of Icotinib on Beneficiary of 
Advanced Non-small Cell Lung Cancer with EGFR Common Mutation].

PubMed

Jiang, Xiaowen; Wang, Wenxian; Zhang, Yiping

2016-04-20

Targeted therapy has become an indispensable therapy method in advanced non-small cell lung cancer (NSCLC) treatment. Epithelial growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) can significantly prolong the survival of patients harboring EGFR gene mutation. Icotinb is China's first EGFR-TKI with independent intellectual property rights. The aim of this study is to investigate the clinical characteristics about the beneficiary of advanced NSCLC patients with EGFR Common mutation who were treated with Icotinib. Retrospectively collect the data about beneficiary [progression-free survival (PFS)≥6 months] and analysis of the related risk factors for prognosis. From September 1, 2011 to September 30, 2015, 231 cases of advanced NSCLC beneficiary with EGFR common mutation were enrolled for treatment with icotinib in Zhejiang Cancer Hospital. The one year benefit rate was 67.9% in the group treated with Icotinib as first line, and in the groupas second line or above was 53.6%, which is statisticallysignificant. The two years benefit rate was 18.7% and 9.3%, respectively. The median PFS of first line group and the second line or above was 16.7 and 12.4 months, respectively. The presence of brain metastasis (P=0.010), Prior chemotherapy (P=0.001), Eastern Cooperative Oncology Group (ECOG) score (P=0.001) were the main factors influencing the prognosis. The most common adverse were skin rashes (51 cases, 22.1%) and diarrhea (27 cases, 11.7%). Icotinib offers long-term clinical benefit and good tolerance for advanced NSCLC harboring EGFR gene mutation. Its advantage groups in addition to the patients with brain metastases and better ECOG score, the curative effect of patients with the first-line treatment is superior to second or further line. 
.

MR Neurography: Advances

PubMed Central

Chhabra, Avneesh; Zhao, Lianxin; Carrino, John A.; Trueblood, Eo; Koceski, Saso; Shteriev, Filip; Lenkinski, Lionel; Sinclair, Christopher D. J.; Andreisek, Gustav

2013-01-01

High resolution and high field magnetic resonance neurography (MR neurography, MRN) is shown to have excellent anatomic capability. There have been considerable advances in the technology in the last few years leading to various feasibility studies using different structural and functional imaging approaches in both clinical and research settings. This paper is intended to be a useful seminar for readers who want to gain knowledge of the advancements in the MRN pulse sequences currently used in clinical practice as well as learn about the other techniques on the horizon aimed at better depiction of nerve anatomy, pathology, and potential noninvasive evaluation of nerve degeneration or regeneration. PMID:23589774

Advances in pediatric dehydration therapy.

PubMed

Niescierenko, Michelle; Bachur, Richard

2013-06-01

To review the advances in the assessment, treatment, and evaluation of care for pediatric dehydration. Recent studies have added new information across the spectrum of care for dehydration. Advances in the assessment of dehydration allow more accurate clinical evaluation, but do not help predict the treatment outcomes. Antiemetics as an adjunct to oral rehydration therapy have been proven well tolerated, efficacious, and cost-effective. Rapid, large-volume intravenous rehydration for outpatients with dehydration did not show any benefit over more standard regimens. Clinical guidelines incorporate all these aspects of care; however, physicians show poor adherence to the guidelines despite the evidence that guidelines improve outcomes and reduce cost. Dehydration burdens the healthcare system worldwide. Through advances in its assessment, treatment with antiemetics and intravenous fluids, and standardization of practice with clinical guidelines, this burden could be reduced.

Multimodal endocavitary ultrasound versus MRI and clinical findings in pre- and post-treatment advanced cervical cancer. Preliminary report.

PubMed

Csutak, Csaba; Badea, Radu; Bolboaca, Sorana D; Ordeanu, Claudia; Nagy, Viorica M; Fekete, Zsolt; Chiorean, Liliana; Dudea, Sorin M

2016-03-01

The aim of this study was to evaluate the use of pre and post-therapy transrectal and transvaginal ultrasonography (TRUS, TVUS) with contrast enhancement and strain elastography compared with clinical examination and magnetic resonance imaging (MRI) in the assessment of advanced stage cervical cancer. This was a prospective study, carried out over a period of nine months on subjects with advanced-stage cervical cancer (stage >/= IIB). All included patients were examined clinically and underwent abdomino-pelvic contrast enhanced MRI and multimodal US examinations (TRUS with strain elastography and contrast enhanced TVUS) at the time of diagnosis and after radiochemotherapy. Tumor size and staging at TRUS and TVUS was compared with the same data obtained by clinical examination and MRI. Pathology was the golden standard. Eight patients accomplished the inclusion criteria. In five cases the tumor stage was identical on clinical and MRI examinations. In all cases parametrial infiltration was diagnosed by all pre-treatment examinations. No significant differences were observed in tumor size between clinical, US and MRI exams either at baseline or post-therapy, in native or post-contrast examinations. The size of the tumor evaluated pre-treatment proved to be significantly smaller post-contrast in both US and MRI examinations compared with the native images. Post-therapy, no significant differences were observed on US measured tumor dimensions when comparing native with post-contrast images. Oppositely, significant smaller dimensions were observed on post-contrast MRI compared with native scans. TRUS is accurate in the estimation of pre-therapy cervical cancer dimension. The post therapy tumor evaluation is better performed with MRI. The use of intravenous contrast agents on both examinations did not improved the accuracy of tumor evaluation pre or post-therapy.

Nonsurgical treatment of moderate and advanced periimplantitis lesions: a controlled clinical study.

PubMed

Schwarz, Frank; Bieling, Katrin; Bonsmann, Martin; Latz, Thilo; Becker, Jürgen

2006-12-01

The aim of this controlled, parallel design clinical study was to evaluate the effectiveness of an Er:YAG (erbium-doped:yttrium, aluminum, and garnet) laser for nonsurgical treatment of periimplantitis lesions. Twenty patients, each of whom displayed at least one implant with (a) moderate and (b) advanced periimplantitis (n=40 implants; IMZ, ITI, Spline Twist, ZL-Duraplant, Camlog), were randomly instrumented nonsurgically using either (1) an Er:YAG laser (100 mJ/pulse, 10 Hz) device (LAS) or (2) mechanical debridement using plastic curettes and antiseptic therapy with chlorhexidine digluconate (0.2%) (C). The following clinical parameters were measured at baseline, 3, 6, and 12 months after treatment: plaque index, bleeding on probing (BOP), probing depth, gingival recession, and clinical attachment level (CAL). Mean BOP improved significantly in both groups at 3, 6, and 12 months (a- lesions: P<0.001 and b- lesions: P<0.01, respectively). After 3 and 6 months, the mean reduction of BOP was significantly higher in the LAS group when compared to the C group (a- and b- lesions: P<0.01 and P<0.05, respectively). At 3 and 6 months, both groups revealed significant CAL gains at a- and b- lesions (P<0.01, respectively). In both groups, however, the mean CAL at a- and b- lesions was not significantly different from the respective baseline values at 12 months (P>0.05, respectively). Although treatment of periimplantitis lesions with LAS resulted in a significantly higher BOP reduction than C, its effectiveness seemed to be limited to a period of 6 months, particularly at b- lesions.

Meckel-Gruber Syndrome: An Update on Diagnosis, Clinical Management, and Research Advances.

PubMed

Hartill, Verity; Szymanska, Katarzyna; Sharif, Saghira Malik; Wheway, Gabrielle; Johnson, Colin A

2017-01-01

Meckel-Gruber syndrome (MKS) is a lethal autosomal recessive congenital anomaly syndrome caused by mutations in genes encoding proteins that are structural or functional components of the primary cilium. Conditions that are caused by mutations in ciliary genes are collectively termed the ciliopathies, and MKS represents the most severe condition in this group of disorders. The primary cilium is a microtubule-based organelle, projecting from the apical surface of vertebrate cells. It acts as an "antenna" that receives and transduces chemosensory and mechanosensory signals, but also regulates diverse signaling pathways, such as Wnt and Shh, that have important roles during embryonic development. Most MKS proteins localize to a distinct ciliary compartment called the transition zone (TZ) that regulates the trafficking of cargo proteins or lipids. In this review, we provide an up-to-date summary of MKS clinical features, molecular genetics, and clinical diagnosis. MKS has a highly variable phenotype, extreme genetic heterogeneity, and displays allelism with other related ciliopathies such as Joubert syndrome, presenting significant challenges to diagnosis. Recent advances in genetic technology, with the widespread use of multi-gene panels for molecular testing, have significantly improved diagnosis, genetic counseling, and the clinical management of MKS families. These include the description of some limited genotype-phenotype correlations. We discuss recent insights into the molecular basis of disease in MKS, since the functions of some of the relevant ciliary proteins have now been determined. A common molecular etiology appears to be disruption of ciliary TZ structure and function, affecting essential developmental signaling and the regulation of secondary messengers.

Hand-in-hand advances in biomedical engineering and sensorimotor restoration.

PubMed

Pisotta, Iolanda; Perruchoud, David; Ionta, Silvio

2015-05-15

Living in a multisensory world entails the continuous sensory processing of environmental information in order to enact appropriate motor routines. The interaction between our body and our brain is the crucial factor for achieving such sensorimotor integration ability. Several clinical conditions dramatically affect the constant body-brain exchange, but the latest developments in biomedical engineering provide promising solutions for overcoming this communication breakdown. The ultimate technological developments succeeded in transforming neuronal electrical activity into computational input for robotic devices, giving birth to the era of the so-called brain-machine interfaces. Combining rehabilitation robotics and experimental neuroscience the rise of brain-machine interfaces into clinical protocols provided the technological solution for bypassing the neural disconnection and restore sensorimotor function. Based on these advances, the recovery of sensorimotor functionality is progressively becoming a concrete reality. However, despite the success of several recent techniques, some open issues still need to be addressed. Typical interventions for sensorimotor deficits include pharmaceutical treatments and manual/robotic assistance in passive movements. These procedures achieve symptoms relief but their applicability to more severe disconnection pathologies is limited (e.g. spinal cord injury or amputation). Here we review how state-of-the-art solutions in biomedical engineering are continuously increasing expectances in sensorimotor rehabilitation, as well as the current challenges especially with regards to the translation of the signals from brain-machine interfaces into sensory feedback and the incorporation of brain-machine interfaces into daily activities. Copyright © 2015 Elsevier B.V. All rights reserved.

Clinical use of an epinephrine-reduced (1/400,000) articaine solution in short-time dental routine treatments--a multicenter study.

PubMed

Daubländer, Monika; Kämmerer, Peer W; Willershausen, Brita; Leckel, Michael; Lauer, Hans-Christoph; Buff, Siegmar; Rösl, Benita

2012-08-01

The addition of epinephrine in dental local anaesthesia results in a longer and deeper anaesthesia under almost ischemic conditions. For short-time dental treatments, epinephrine-reduced anaesthetics may offer shorter and more individual anaesthesia with reduced potential side effects. The aim of this study was a clinical evaluation of anaesthetic potency and adverse effects of an epinephrine-reduced articaine formulation in dental patients undergoing short-time routine treatment. In a prospective clinical, not interventional, study between January 2008 and February 2009, 908 patients undergoing short-time dental treatment in five medical centers were anaesthetized with 4% articaine 1:400,000 epinephrine (Ubistesin, 3M/ESPE, Seefeld, Germany). Efficacy and safety in clinical use were evaluated. A follow-up after 1 day was conducted by telephone survey. A mean amount of 1.3-ml anaesthetic solution was needed to achieve a complete or sufficient anaesthesia in 97% (n = 876) of cases. A second injection had to be done in 3.7% (n = 34) before and in 11.9% (n = 108) during treatment. Here, the second injection had to be applied after a mean of 48.6 min. The mean duration of soft tissue anaesthesia after infiltration was 146.6 min, after nerve block 187.7 min. The painful treatment took a mean of 50.2 min and the total treatment time summed up to 68.8 min. In 1.7% cases (n = 15), unwanted side effects were observed. The results indicate that a lower concentration of epinephrine in combination with the 4% articaine solution leads to a high success rate of efficacy. The clinical use of a 4% articaine 1:400,000 epinephrine solution can be stated as safe and effective in short dental routine treatments. Reconsiderations concerning limitations of indication or additional contraindications are not necessary.

Tissue-Engineered Solutions in Plastic and Reconstructive Surgery: Principles and Practice

PubMed Central

Al-Himdani, Sarah; Jessop, Zita M.; Al-Sabah, Ayesha; Combellack, Emman; Ibrahim, Amel; Doak, Shareen H.; Hart, Andrew M.; Archer, Charles W.; Thornton, Catherine A.; Whitaker, Iain S.

2017-01-01

Recent advances in microsurgery, imaging, and transplantation have led to significant refinements in autologous reconstructive options; however, the morbidity of donor sites remains. This would be eliminated by successful clinical translation of tissue-engineered solutions into surgical practice. Plastic surgeons are uniquely placed to be intrinsically involved in the research and development of laboratory engineered tissues and their subsequent use. In this article, we present an overview of the field of tissue engineering, with the practicing plastic surgeon in mind. The Medical Research Council states that regenerative medicine and tissue engineering “holds the promise of revolutionizing patient care in the twenty-first century.” The UK government highlighted regenerative medicine as one of the key eight great technologies in their industrial strategy worthy of significant investment. The long-term aim of successful biomanufacture to repair composite defects depends on interdisciplinary collaboration between cell biologists, material scientists, engineers, and associated medical specialties; however currently, there is a current lack of coordination in the field as a whole. Barriers to translation are deep rooted at the basic science level, manifested by a lack of consensus on the ideal cell source, scaffold, molecular cues, and environment and manufacturing strategy. There is also insufficient understanding of the long-term safety and durability of tissue-engineered constructs. This review aims to highlight that individualized approaches to the field are not adequate, and research collaboratives will be essential to bring together differing areas of expertise to expedite future clinical translation. The use of tissue engineering in reconstructive surgery would result in a paradigm shift but it is important to maintain realistic expectations. It is generally accepted that it takes 20–30 years from the start of basic science research to clinical utility

Tissue-Engineered Solutions in Plastic and Reconstructive Surgery: Principles and Practice.

PubMed

Al-Himdani, Sarah; Jessop, Zita M; Al-Sabah, Ayesha; Combellack, Emman; Ibrahim, Amel; Doak, Shareen H; Hart, Andrew M; Archer, Charles W; Thornton, Catherine A; Whitaker, Iain S

2017-01-01

Recent advances in microsurgery, imaging, and transplantation have led to significant refinements in autologous reconstructive options; however, the morbidity of donor sites remains. This would be eliminated by successful clinical translation of tissue-engineered solutions into surgical practice. Plastic surgeons are uniquely placed to be intrinsically involved in the research and development of laboratory engineered tissues and their subsequent use. In this article, we present an overview of the field of tissue engineering, with the practicing plastic surgeon in mind. The Medical Research Council states that regenerative medicine and tissue engineering "holds the promise of revolutionizing patient care in the twenty-first century." The UK government highlighted regenerative medicine as one of the key eight great technologies in their industrial strategy worthy of significant investment. The long-term aim of successful biomanufacture to repair composite defects depends on interdisciplinary collaboration between cell biologists, material scientists, engineers, and associated medical specialties; however currently, there is a current lack of coordination in the field as a whole. Barriers to translation are deep rooted at the basic science level, manifested by a lack of consensus on the ideal cell source, scaffold, molecular cues, and environment and manufacturing strategy. There is also insufficient understanding of the long-term safety and durability of tissue-engineered constructs. This review aims to highlight that individualized approaches to the field are not adequate, and research collaboratives will be essential to bring together differing areas of expertise to expedite future clinical translation. The use of tissue engineering in reconstructive surgery would result in a paradigm shift but it is important to maintain realistic expectations. It is generally accepted that it takes 20-30 years from the start of basic science research to clinical utility

'You can't just hit a button': an ethnographic study of strategies to repurpose data from advanced clinical information systems for clinical process improvement.

PubMed

Morrison, Cecily; Jones, Matthew; Jones, Rachel; Vuylsteke, Alain

2013-04-10

Current policies encourage healthcare institutions to acquire clinical information systems (CIS) so that captured data can be used for secondary purposes, including clinical process improvement. Such policies do not account for the extra work required to repurpose data for uses other than direct clinical care, making their implementation problematic. This paper aims to analyze the strategies employed by clinical units to use data effectively for both direct clinical care and clinical process improvement. Ethnographic methods were employed. A total of 54 contextual interviews with health professionals spanning various disciplines and 18 hours of observation were carried out in 5 intensive care units in England using an advanced CIS. Case studies of how the extra work was achieved in each unit were derived from the data and then compared. We found that extra work is required to repurpose CIS data for clinical process improvement. Health professionals must enter data not required for clinical care and manipulation of this data into a machine-readable form is often necessary. Ambiguity over who should be responsible for this extra work hindered CIS data usage for clinical process improvement. We describe 11 strategies employed by units to accommodate this extra work, distributing it across roles. Seven of these motivated data entry by health professionals and four addressed the machine readability of data. Many of the strategies relied heavily on the skill and leadership of local clinical customizers. To realize the expected clinical process improvements by the use of CIS data, clinical leaders and policy makers need to recognize and support the redistribution of the extra work that is involved in data repurposing. Adequate time, funding, and appropriate motivation are needed to enable units to acquire and deliver the necessary skills in CIS customization.

Review of advanced driver assistance systems (ADAS)

NASA Astrophysics Data System (ADS)

Ziebinski, Adam; Cupek, Rafal; Grzechca, Damian; Chruszczyk, Lukas

2017-11-01

New cars can be equipped with many advanced safety solutions. Airbags, seatbelts and all of the essential passive safety parts are standard equipment. Now cars are often equipped with new advanced active safety systems that can prevent accidents. The functions of the Advanced Driver Assistance Systems are still growing. A review of the most popular available technologies used in ADAS and descriptions of their application areas are discussed in this paper.

Introduction to special section of the Journal of Family Psychology, advances in mixed methods in family psychology: integrative and applied solutions for family science.

PubMed

Weisner, Thomas S; Fiese, Barbara H

2011-12-01

Mixed methods in family psychology refer to the systematic integration of qualitative and quantitative techniques to represent family processes and settings. Over the past decade, significant advances have been made in study design, analytic strategies, and technological support (such as software) that allow for the integration of quantitative and qualitative methods and for making appropriate inferences from mixed methods. This special section of the Journal of Family Psychology illustrates how mixed methods may be used to advance knowledge in family science through identifying important cultural differences in family structure, beliefs, and practices, and revealing patterns of family relationships to generate new measurement paradigms and inform clinical practice. Guidance is offered to advance mixed methods research in family psychology through sound principles of peer review.

An advanced analytical solution for pressure build-up during CO2 injection into infinite saline aquifers: The role of compressibility

NASA Astrophysics Data System (ADS)

Wu, Haiqing; Bai, Bing; Li, Xiaochun

2018-02-01

Existing analytical or approximate solutions that are appropriate for describing the migration mechanics of CO2 and the evolution of fluid pressure in reservoirs do not consider the high compressibility of CO2, which reduces their calculation accuracy and application value. Therefore, this work first derives a new governing equation that represents the movement of complex fluids in reservoirs, based on the equation of continuity and the generalized Darcy's law. A more rigorous definition of the coefficient of compressibility of fluid is then presented, and a power function model (PFM) that characterizes the relationship between the physical properties of CO2 and the pressure is derived. Meanwhile, to avoid the difficulty of determining the saturation of fluids, a method that directly assumes the average relative permeability of each fluid phase in different fluid domains is proposed, based on the theory of gradual change. An advanced analytical solution is obtained that includes both the partial miscibility and the compressibility of CO2 and brine in evaluating the evolution of fluid pressure by integrating within different regions. Finally, two typical sample analyses are used to verify the reliability, improved nature and universality of this new analytical solution. Based on the physical characteristics and the results calculated for the examples, this work elaborates the concept and basis of partitioning for use in further work.

Apatinib: A Review in Advanced Gastric Cancer and Other Advanced Cancers.

PubMed

Scott, Lesley J

2018-05-01

Apatinib [Aitan ® (brand name in China)], also known as rivoceranib, is a novel, small molecule, selective vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor and is the second anti-angiogenic drug to be approved in China for the treatment of advanced or metastatic gastric cancer. This article summarizes the pharmacological properties of apatinib and reviews its clinical use in chemotherapy-experienced patients with advanced gastric adenocarcinoma, including gastroesophageal adenocarcinoma (GEA), or with other advanced cancers such as non-small cell lung cancer (NSCLC), breast cancer, gynaecological cancers, hepatocellular carcinoma (HCC), thyroid cancer and sarcomas. As third- or subsequent-line therapy, oral apatinib significantly prolonged median progression-free survival (PFS) and overall survival (OS) compared with placebo and had a manageable safety profile in Chinese patients with advanced or metastatic gastric cancer or GEA participating in randomized, double-blind, multicentre, phase 2 and 3 trials. More limited evidence also supports it use as subsequent-line treatment in Chinese patients with other advanced or metastatic solid tumours, including NSCLC, breast cancer and HCC. Further clinical experience and long-term pharmacovigilance data are required to more definitively establish the efficacy and safety profile of apatinib, including its use in combination with other chemotherapy agents and its role in the management of other types of advanced or metastatic solid tumours. In the meantime, given its convenient administration regimen and the limited treatment options and poor prognosis for patients with advanced or metastatic solid tumours, apatinib is an important, emerging treatment option for adult patients with advanced gastric adenocarcinoma or GEA who have progressed or relapsed after chemotherapy.

Challenges of advanced hepatocellular carcinoma

PubMed Central

Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

2016-01-01

Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID:27678348

Solution Structure of the Soluble Receptor for Advanced Glycation End Products (sRAGE)*

PubMed Central

Sárkány, Zsuzsa; Ikonen, Teemu P.; Ferreira-da-Silva, Frederico; Saraiva, Maria João; Svergun, Dmitri; Damas, Ana Margarida

2011-01-01

The receptor for advanced glycation end products (RAGE) is a multiligand cell surface receptor involved in various human diseases, as it binds to numerous molecules and proteins that modulate the activity of other proteins. Elucidating the three-dimensional structure of this receptor is therefore most important for understanding its function during activation and cellular signaling. The major alternative splice product of RAGE comprises its extracellular region that occurs as a soluble protein (sRAGE). Although the structures of sRAGE domains were available, their assembly into the functional full-length protein remained unknown. We observed that the protein has concentration-dependent oligomerization behavior, and this is also mediated by the presence of Ca2+ ions. Moreover, using synchrotron small angle x-ray scattering, the solution structure of human sRAGE was determined in the monomeric and dimeric forms. The model for the monomer displays a J-like shape, whereas the dimer is formed through the association of the two N-terminal domains and has an elongated structure. These results provide insights into the assembly of the RAGE homodimer, which is essential for signal transduction, and the sRAGE:RAGE heterodimer that leads to blockage of the receptor signaling, paving the way for the design of therapeutic strategies for a large number of different pathologies. PMID:21865159

Clinical management and outcome of patients with advanced NSCLC carrying EGFR mutations in Spain.

PubMed

Arriola, Edurne; García Gómez, Ramón; Diz, Pilar; Majem, Margarita; Martínez Aguillo, Maite; Valdivia, Javier; Paredes, Alfredo; Sánchez-Torres, José Miguel; Peralta Muñoz, Sergio; Barneto, Isidoro; Gutierrez, Vanesa; Andrade Santiago, Jesús Manuel; Aparisi, Francisco; Isla, Dolores; Ponce, Santiago; Vicente Baz, David; Artal, Angel; Amador, Mariluz; Provencio, Mariano

2018-01-30

Although the benefit of first-line epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) over chemotherapy has been demonstrated in several clinical trials, data from clinical practice is lacking and the optimal EGFR TKI to be used remains unclear. This study aims to assess the real-life diagnostic and clinical management and outcome of patients with advanced non-small-cell lung cancer (NSCLC) carrying EGFR mutations in Spain. All consecutive patients recently diagnosed with advanced or metastatic NSCLC from April 2010 to December 2011 in 18 Spanish hospitals and carrying EGFR mutations were retrospectively evaluated. Between March and November 2013, a total of 187 patients were enrolled (98.3% Caucasian, 61.9% female, 54.9% never-smokers, 89.0% adenocarcinoma). Mutation testing was mainly performed on biopsy tumour tissue specimens (69.0%) using a qPCR-based test (90%) (47.0% Therascreen EGFR PCR Kit). Common sensitising mutations were detected in 79.8% of patients: 57.1% had exon 19 deletions and 22.6% exon 21 L858R point mutations. The vast majority of patients received first-line therapy (n = 168; 92.8%). EGFR TKIs were the most commonly used first-line treatment (81.5%), while chemotherapy was more frequently administered as a second- and third-line option (51.9% and 56.0%, respectively). Of 141 patients who experienced disease progression, 79 (56.0%) received second-line treatment. After disease progression on first-line TKIs (n = 112), 33.9% received chemotherapy, 8.9% chemotherapy and a TKI, and 9.8% continued TKI therapy. Most patients received first-line gefitinib (83.0%), while erlotinib was more frequently used in the second-line setting (83.0%). Progression-free survival (PFS) and overall survival (OS) in patients harbouring common mutations were 11.1 months and 20.1 months respectively (exon 19 deletions: 12.4 and 21.4 months; L858R: 8.3 and 14.5 months), and 3.9 months and 11.1 months respectively for those with rare

Predictors of Locally Advanced Disease at Presentation and Clinical Outcomes Among Cervical Cancer Patients Admitted at a Tertiary Hospital in Botswana.

PubMed

Nassali, Mercy Nkuba; Tadele, Melese; Nkuba, Robert Michael; Modimowame, Jamieson; Enyeribe, Iwuh; Katse, Edwin

2018-05-23

The aim of this study was to determine predictors of locally advanced disease at presentation and clinical outcomes among cervical cancer patients in Botswana to inform interventional strategies. Retrospective review of 149 medical records of new cervical cancer patients was conducted between August 2016 and February 2017 at the Princess Marina Hospital. Data collected included sociodemographics, presenting symptoms, stage of disease, comorbidities, interventions, and clinical outcomes. STATA 12 was used for data analysis. Frequencies were used to describe patient demographics and clinical variables. Bivariate and multivariate binary logistic regression analyses were used to determine association between stage of disease at presentation and patient characteristics. P ≤ 0.05 was considered significant. Mean age was 49.5 years. Nine (89.2%) in 10 patients had locally advanced cervical cancer (stage IB1-IVB). Two thirds (65.1%) were human immunodeficiency virus positive. Previous cervical cancer screening was low at 38.3%. Common symptoms were abnormal vaginal bleeding, low abdominal pain, and malodorous vaginal discharge reported among 75.8%, 66.4%, and 39.6% of cases, respectively. Overall, 32 (21.5%) were declared cured, 52 (34.9%) improved, and 11 (7.4%) opted for home-based care. Hospital deaths were 41 (27.5%). Major causes of death were renal failure (48.7%) and severe anemia (39%). Thirteen (8.7%) were lost to follow-up. Being unmarried (odds ratio [OR], 3.9), lack of cervical cancer screening (OR, 6.68), presentation with vaginal bleeding (OR, 7.69), and low abdominal pain (OR, 4.69) were associated with advanced disease at presentation. Lack of cervical cancer screening, vaginal bleeding, low abdominal pain, and unmarried status were associated with advanced disease at presentation. We recommend scale-up of cervical cancer screening and its integration into routine human immunodeficiency virus care. Capacity building in gynecologic oncology and palliative

Semiautomated Workflow for Clinically Streamlined Glioma Parametric Response Mapping

PubMed Central

Keith, Lauren; Ross, Brian D.; Galbán, Craig J.; Luker, Gary D.; Galbán, Stefanie; Zhao, Binsheng; Guo, Xiaotao; Chenevert, Thomas L.; Hoff, Benjamin A.

2017-01-01

Management of glioblastoma multiforme remains a challenging problem despite recent advances in targeted therapies. Timely assessment of therapeutic agents is hindered by the lack of standard quantitative imaging protocols for determining targeted response. Clinical response assessment for brain tumors is determined by volumetric changes assessed at 10 weeks post-treatment initiation. Further, current clinical criteria fail to use advanced quantitative imaging approaches, such as diffusion and perfusion magnetic resonance imaging. Development of the parametric response mapping (PRM) applied to diffusion-weighted magnetic resonance imaging has provided a sensitive and early biomarker of successful cytotoxic therapy in brain tumors while maintaining a spatial context within the tumor. Although PRM provides an earlier readout than volumetry and sometimes greater sensitivity compared with traditional whole-tumor diffusion statistics, it is not routinely used for patient management; an automated and standardized software for performing the analysis and for the generation of a clinical report document is required for this. We present a semiautomated and seamless workflow for image coregistration, segmentation, and PRM classification of glioblastoma multiforme diffusion-weighted magnetic resonance imaging scans. The software solution can be integrated using local hardware or performed remotely in the cloud while providing connectivity to existing picture archive and communication systems. This is an important step toward implementing PRM analysis of solid tumors in routine clinical practice. PMID:28286871

Discharge of Non-Acute Coronary Syndrome Chest Pain Patients From Emergency Care to an Advanced Nurse Practitioner-Led Chest Pain Clinic: A Cross-Sectional Study of Referral Source and Final Diagnosis.

PubMed

Ingram, Shirley J; McKee, Gabrielle; Quirke, Mary B; Kelly, Niamh; Moloney, Ashling

Chest pain is a common presentation to emergency departments (EDs). Pathways for patients with non-acute coronary syndrome (ACS) chest pain are not optimal. An advanced cardiology nurse-led chest pain service was commenced to address this. The aim of the study was to assess the outcomes of non-ACS patients discharged from ED to an advanced cardiology nurse-led chest pain clinic and compare by referral type (nurse or ED physician). The service consisted of advanced cardiology nurse or ED physician consultation in the ED and discharge to advanced nurse-led chest pain clinic review less than 72 hours after discharge. Referrals were by the advanced nurses during consult hours and out-of-hours were by the ED physicians. Data were extracted from case notes. This was a 1-site cross-sectional study of patients attending the chest pain clinic over 2 years. Confirmed coronary disease was diagnosed in 24% of patients. Of the 1041 patients, 45% were referred by the advanced nurses, who referred significantly more patients who were older (56.5 years/52.3 years), had positive exercise stress test results (21%/12%), and were diagnosed with stable coronary artery disease (19%/11%) and less patients with musculoskeletal diagnosis (5%/13%) and other noncardiac pain (36%/45%). The study fills a gap in the literature on the follow up of non-ACS patients who present to ED and used advanced cardiology nursing expertise in the ED and chest pain clinic. The advanced nurse referred more patients who were diagnosed with coronary disease, reflecting the expertise, experience, and efficiency of the advanced cardiology nurse-led service.

Methylphenidate hydrochloride improves cognitive function in patients with advanced cancer and hypoactive delirium: a prospective clinical study

PubMed Central

Gagnon, Bruno; Low, Graeme; Schreier, Gil

2005-01-01

Objective To investigate the clinical improvement observed in patients with advanced cancer and hypoactive delirium after the administration of methylphenidate hydrochloride. Methods Fourteen patients with advanced cancer and hypoactive delirium were seen between March 1999 and August 2000 at the Palliative Care Day Hospital and the inpatient Tertiary Palliative Care Unit of Montreal General Hospital, Montréal. They were chosen for inclusion in a prospective clinical study on the basis of (1) cognitive failure documented by the Mini-Mental State Examination (MMSE), (2) sleep–wake pattern disturbances, (3) psychomotor retardation, (4) absence of delusions or hallucinations, and (5) absence of an underlying cause to explain the delirium. All patients were treated with methylphenidate, and changes in their cognitive function were measured using the MMSE. Results All 14 patients showed improvement in their cognitive function as documented by the MMSE. The median pretreatment MMSE score (maximum score 30) was 21 (mean 20.9, standard deviation [SD] 4.9), which improved to a median of 27 (mean 24.9, SD 4.7) after the first dose of methylphenidate (p < 0.001, matched, paired Wilcoxon signed rank test). One patient died before reaching a stable dose of methylphenidate. In the other 13 patients, the median MMSE score further improved to 28 (mean 27.8, SD 2.4) (p = 0.02 compared with the median MMSE score documented 1 hour after the first dose of methylphenidate). All patients showed an improvement in psychomotor activities. Conclusions Hypoactive delirium that cannot be explained by an underlying cause (metabolic or drug-induced) in patients with advanced cancer appears to be a specific syndrome that could be improved by the administration of methylphenidate. PMID:15798785

Analytic validation and real-time clinical application of an amplicon-based targeted gene panel for advanced cancer

PubMed Central

Wing, Michele R.; Reeser, Julie W.; Smith, Amy M.; Reeder, Matthew; Martin, Dorrelyn; Jewell, Benjamin M.; Datta, Jharna; Miya, Jharna; Monk, J. Paul; Mortazavi, Amir; Otterson, Gregory A.; Goldberg, Richard M.; VanDeusen, Jeffrey B.; Cole, Sharon; Dittmar, Kristin; Jaiswal, Sunny; Kinzie, Matthew; Waikhom, Suraj; Freud, Aharon G.; Zhou, Xiao-Ping; Chen, Wei; Bhatt, Darshna; Roychowdhury, Sameek

2017-01-01

Multiplex somatic testing has emerged as a strategy to test patients with advanced cancer. We demonstrate our analytic validation approach for a gene hotspot panel and real-time prospective clinical application for any cancer type. The TruSight Tumor 26 assay amplifies 85 somatic hotspot regions across 26 genes. Using cell line and tumor mixes, we observed that 100% of the 14,715 targeted bases had at least 1000x raw coverage. We determined the sensitivity (100%, 95% CI: 96-100%), positive predictive value (100%, 95% CI: 96-100%), reproducibility (100% concordance), and limit of detection (3% variant allele frequency at 1000x read depth) of this assay to detect single nucleotide variants and small insertions and deletions. Next, we applied the assay prospectively in a clinical tumor sequencing study to evaluate 174 patients with metastatic or advanced cancer, including frozen tumors, formalin-fixed tumors, and enriched peripheral blood mononuclear cells in hematologic cancers. We reported one or more somatic mutations in 89 (53%) of the sequenced tumors (167 passing quality filters). Forty-three of these patients (26%) had mutations that would enable eligibility for targeted therapies. This study demonstrates the validity and feasibility of applying TruSight Tumor 26 for pan-cancer testing using multiple specimen types. PMID:29100271

Clinical social networking--a new revolution in provider communication and delivery of clinical information across providers of care?

PubMed

Kolowitz, Brian J; Lauro, Gonzalo Romero; Venturella, James; Georgiev, Veliyan; Barone, Michael; Deible, Christopher; Shrestha, Rasu

2014-04-01

The adoption of social media technologies appears to enhance clinical outcomes through improved communications as reported by Bacigalupe (Fam Syst Heal 29(1):1-14, 2011). The ability of providers to more effectively, directly, and rapidly communicate among themselves as well as with patients should strengthen collaboration and treatment as reported by Bacigalupe (Fam Syst Heal 29(1):1-14, 2011). This paper is a case study in one organization's development of an internally designed and developed social technology solution termed "Unite." The Unite system combines social technologies' features including push notifications, messaging, community groups, and user lists with clinical workflow and applications to construct dynamic provider networks, simplify communications, and facilitate clinical workflow optimization. Modeling Unite as a social technology may ease adoption barriers. Developing a social network that is integrated with healthcare information systems in the clinical space opens the doors to capturing and studying the way in which providers communicate. The Unite system appears to have the potential to breaking down existing communication paradigms. With Unite, a rich set of usage data tied to clinical events may unravel alternative networks that can be leveraged to advance patient care.

Advances in dental materials.

PubMed

Fleming, Garry J P

2014-05-01

The dental market is replete with new resorative materials marketed on the basis of novel technological advances in materials chemistry, bonding capability or reduced operator time and/or technique sensitivity. This paper aims to consider advances in current materials, with an emphasis on their role in supporting contemporary clinical practice.

Effect of the PREPARE Website vs an Easy-to-Read Advance Directive on Advance Care Planning Documentation and Engagement Among Veterans: A Randomized Clinical Trial.

PubMed

Sudore, Rebecca L; Boscardin, John; Feuz, Mariko A; McMahan, Ryan D; Katen, Mary T; Barnes, Deborah E

2017-08-01

Documentation rates of patients' medical wishes are often low. It is unknown whether easy-to-use, patient-facing advance care planning (ACP) interventions can overcome barriers to planning in busy primary care settings. To compare the efficacy of an interactive, patient-centered ACP website (PREPARE) with an easy-to-read advance directive (AD) to increase planning documentation. This was a comparative effectiveness randomized clinical trial from April 2013 to July 2016 conducted at multiple primary care clinics at the San Francisco VA Medical Center. Inclusion criteria were age of a least 60 years; at least 2 chronic and/or serious conditions; and 2 or more primary care visits; and 2 or more additional clinic, hospital, or emergency room visits in the last year. Participants were randomized to review PREPARE plus an easy-to-read AD or the AD alone. There were no clinician and/or system-level interventions or education. Research staff were blinded for all follow-up measurements. The primary outcome was new ACP documentation (ie, legal forms and/or discussions) at 9 months. Secondary outcomes included patient-reported ACP engagement at 1 week, 3 months, and 6 months using validated surveys of behavior change process measures (ie, 5-point knowledge, self-efficacy, readiness scales) and action measures (eg, surrogate designation, using a 0-25 scale). We used intention-to-treat, mixed-effects logistic and linear regression, controlling for time, health literacy, race/ethnicity, baseline ACP, and clustering by physician. The mean (SD) age of 414 participants was 71 (8) years, 38 (9%) were women, 83 (20%) had limited literacy, and 179 (43%) were nonwhite. No participant characteristic differed significantly among study arms at baseline. Retention at 6 months was 90%. Advance care planning documentation 6 months after enrollment was higher in the PREPARE arm vs the AD-alone arm (adjusted 35% vs 25%; odds ratio, 1.61 [95% CI, 1.03-2.51]; P = .04). PREPARE also resulted

Flipped Classrooms for Advanced Science Courses

NASA Astrophysics Data System (ADS)

Tomory, Annette; Watson, Sunnie Lee

2015-12-01

This article explains how issues regarding dual credit and Advanced Placement high school science courses could be mitigated via a flipped classroom instructional model. The need for advanced high school courses will be examined initially, followed by an analysis of advanced science courses and the reform they are experiencing. Finally, it will conclude with an explanation of flipped classes as well as how they may be a solution to the reform challenges teachers are experiencing as they seek to incorporate more inquiry-based activities.

Do patients discharged from advanced practice physiotherapy-led clinics re-present to specialist medical services?

PubMed

Chang, Angela T; Gavaghan, Belinda; O'Leary, Shaun; McBride, Liza-Jane; Raymer, Maree

2017-05-15

Objective The aim of the present study was to determine the rates of re-referral to specialist out-patient clinics for patients previously managed and discharged from an advanced practice physiotherapy-led service in three metropolitan hospitals. Methods A retrospective audit was undertaken of 462 patient cases with non-urgent musculoskeletal conditions discharged between 1 April 2014 and 30 March 2015 from three metropolitan hospitals. These patients had been discharged from the physiotherapy-led service without requiring specialist medical review. Rates and patterns of re-referral to specialist orthopaedic, neurosurgical, chronic pain, or rheumatology services within 12 months of discharge were investigated. Results Forty-six of the 462 patients (10.0%) who were managed by the physiotherapy-led service were re-referred to specialist medical orthopaedic, neurosurgical, chronic pain or rheumatology departments within 12 months of discharge. Only 22 of these patients (4.8%) were re-referred for the same condition as managed previously and discharged. Conclusions Ninety-five per cent of patients with non-urgent musculoskeletal conditions managed by an advanced practice physiotherapy-led service at three metropolitan hospitals did not re-present to access public specialist medical services for the same condition within 12 months of discharge. This is the first time that re-presentation rates have been reported for patients managed in advanced practice physiotherapy services and the findings support the effectiveness of these models of care in managing demand for speciality out-patient services. What is known about the topic? Advanced practice physiotherapy-led services have been implemented to address the needs of patients referred with non-urgent musculoskeletal conditions to hospital specialist out-patient services. Although this model is widely used in Australia, there has been very little information about whether patients managed in these services subsequently re

Advanced Neuroimaging in Traumatic Brain Injury

PubMed Central

Edlow, Brian L.; Wu, Ona

2013-01-01

Advances in structural and functional neuroimaging have occurred at a rapid pace over the past two decades. Novel techniques for measuring cerebral blood flow, metabolism, white matter connectivity, and neural network activation have great potential to improve the accuracy of diagnosis and prognosis for patients with traumatic brain injury (TBI), while also providing biomarkers to guide the development of new therapies. Several of these advanced imaging modalities are currently being implemented into clinical practice, whereas others require further development and validation. Ultimately, for advanced neuroimaging techniques to reach their full potential and improve clinical care for the many civilians and military personnel affected by TBI, it is critical for clinicians to understand the applications and methodological limitations of each technique. In this review, we examine recent advances in structural and functional neuroimaging and the potential applications of these techniques to the clinical care of patients with TBI. We also discuss pitfalls and confounders that should be considered when interpreting data from each technique. Finally, given the vast amounts of advanced imaging data that will soon be available to clinicians, we discuss strategies for optimizing data integration, visualization and interpretation. PMID:23361483

Advances in clinical study of curcumin.

PubMed

Yang, Chunfen; Su, Xun; Liu, Anchang; Zhang, Lin; Yu, Aihua; Xi, Yanwei; Zhai, Guangxi

2013-01-01

Curcumin has been estimated as a potential agent for many diseases and attracted great attention owing to its various pharmacological activities, including anti-cancer, and anti-inflammatory. Now curcumin is being applied to a number of patients with breast cancer, rheumatoid arthritis, Alzheimer's disease, colorectal cancer, psoriatic, etc. Several clinical trials have stated that curcumin is safe enough and effective. The objective of this article was to summarize the clinical studies of curcumin, and give a reference for future studies.

[Clinical Observation of Icotinib Hydrochloride for Advanced Non-small Cell Lung Cancer Patients with EGFR Status Identified].

PubMed

Li, Xi; Qin, Na; Wang, Jinghui; Yang, Xinjie; Zhang, Xinyong; Lv, Jialin; Wu, Yuhua; Zhang, Hui; Nong, Jingying; Zhang, Quan; Zhang, Shucai

2015-12-01

Icotinib is the first self-developed small molecular drug in China for targeted therapy of lung cancer. Compared to the other two commercially available epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, icotinib is similar to them in chemical structure, mechanism of activity and therapeutic effects. To explore the efficacy and side effects of icotinib hydrochloride in the treatment of the advanced non-small cell lung cancer (NSCLC) patients with EGFR mutation and wild-type. Patients with advanced NSCLC who were treated with icotinib hydrochloride in Beijing Chest Hospital were retrospective analyzed from March 2009 to December 2014. The clinical data of 124 patients (99 with EGFR mutation and 25 with wild type) with advanced NSCLC were enrolled in this study. The patients' overall objective response rate (ORR) was 51.6 % and the disease control rate (DCR) was 79.8%; The patients with EGFR mutation, ORR was 63.6%, DCR was 93.9%. The ORR was 4.0% and the DCR was 24.0% in the wild-type patients. Median progression-free survival (PFS) with icotinib treatment in EGFR mutation patients was 10.5 months and 1.0 month in wild-type patients. The major adverse events were mild skin rash (30.6%) and diarrhea (16.1%). Monotherapy with icotinib hydrochloride is effective and tolerable for the advanced NSCLC EGFR mutation patients.


Advances in clinical and molecular understanding of the FMR1 premutation and fragile X-associated tremor/ataxia syndrome

PubMed Central

Hagerman, Randi; Hagerman, Paul

2014-01-01

Summary Fragile X syndrome, the leading heritable form of cognitive impairment, is caused by epigenetic silencing of the fragile X (FMR1) gene consequent to large expansions (>200 repeats) of a non-coding CGG-repeat element. Smaller, “premutation” expansions (55–200 repeats) can give rise to a family of neurodevelopmental (ADHD, autism spectrum disorder, seizure disorder) and neurodegenerative (FXTAS) clinical phenotypes through an entirely distinct molecular mechanism involving increased FMR1 mRNA production and toxicity. Basic cellular, animal, and human studies have helped to elucidate the underlying RNA toxicity mechanism, while clinical research is providing a more nuanced picture of the spectrum of clinical involvement. Whereas advances on both mechanistic and clinical fronts are driving new approaches to targeted treatment, two important issues/needs are emerging: to define the extent to which the mechanisms contributing to FXTAS also contribute to other neurodegenerative and medical disorders, and to redefine FXTAS in light of its differing presentations and associated features. PMID:23867198

Computers and clinical arrhythmias.

PubMed

Knoebel, S B; Lovelace, D E

1983-02-01

Cardiac arrhythmias are ubiquitous in normal and abnormal hearts. These disorders may be life-threatening or benign, symptomatic or unrecognized. Arrhythmias may be the precursor of sudden death, a cause or effect of cardiac failure, a clinical reflection of acute or chronic disorders, or a manifestation of extracardiac conditions. Progress is being made toward unraveling the diagnostic and therapeutic problems involved in arrhythmogenesis. Many of the advances would not be possible, however, without the availability of computer technology. To preserve the proper balance and purposeful progression of computer usage, engineers and physicians have been exhorted not to work independently in this field. Both should learn some of the other's trade. The two disciplines need to come together to solve important problems with computers in cardiology. The intent of this article was to acquaint the practicing cardiologist with some of the extant and envisioned computer applications and some of the problems with both. We conclude that computer-based database management systems are necessary for sorting out the clinical factors of relevance for arrhythmogenesis, but computer database management systems are beset with problems that will require sophisticated solutions. The technology for detecting arrhythmias on routine electrocardiograms is quite good but human over-reading is still required, and the rationale for computer application in this setting is questionable. Systems for qualitative, continuous monitoring and review of extended time ECG recordings are adequate with proper noise rejection algorithms and editing capabilities. The systems are limited presently for clinical application to the recognition of ectopic rhythms and significant pauses. Attention should now be turned to the clinical goals for detection and quantification of arrhythmias. We should be asking the following questions: How quantitative do systems need to be? Are computers required for the detection of

Advanced Parkinson's disease: clinical characteristics and treatment. Part II.

PubMed

Kulisevsky, J; Luquin, M R; Arbelo, J M; Burguera, J A; Carrillo, F; Castro, A; Chacón, J; García-Ruiz, P J; Lezcano, E; Mir, P; Martinez-Castrillo, J C; Martínez-Torres, I; Puente, V; Sesar, A; Valldeoriola-Serra, F; Yañez, R

2013-01-01

Many patients who have had Parkinson's disease (PD) for several years will present severe motor fluctuations and dyskinesias which require more aggressive therapies. The different approaches which are now available include deep brain stimulation of the subthalamic nucleus or medial globus pallidus, subcutaneous infusion of apomorphine, and intestinal infusion of levodopa-carbidopa. To define the indications and results for the 3 available therapies for advanced PD. Exhaustive review of the literature concerning the indications and results of deep brain stimulation, subcutaneous apomorphine infusion and duodenal infusion of levodopa/carbidopa gel to treat patients with advanced Parkinson disease. Although numerous studies have confirmed the efficacy of the 3 different therapies in advanced PD, there are no comparative studies that would allow us to define the best candidate for each technique. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction

PubMed Central

Margulies, Kenneth B.; Hernandez, Adrian F.; Redfield, Margaret M.; Givertz, Michael M.; Oliveira, Guilherme H.; Cole, Robert; Mann, Douglas L.; Whellan, David J.; Kiernan, Michael S.; Felker, G. Michael; McNulty, Steven E.; Anstrom, Kevin J.; Shah, Monica R.; Braunwald, Eugene; Cappola, Thomas P.

2016-01-01

IMPORTANCE Abnormal cardiac metabolism contributes to the pathophysiology of advanced heart failure with reduced left ventricular ejection fraction (LVEF). Glucagon-like peptide 1 (GLP-1) agonists have shown cardioprotective effects in early clinical studies of patients with advanced heart failure, irrespective of type 2 diabetes status. OBJECTIVE To test whether therapy with a GLP-1 agonist improves clinical stability following hospitalization for acute heart failure. DESIGN, SETTING, AND PARTICIPANTS Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with established heart failure and reduced LVEF who were recently hospitalized. Patients were enrolled between August 2013 and March 2015 at 24 US sites. INTERVENTIONS The GLP-1 agonist liraglutide (n = 154) or placebo (n = 146) via a daily subcutaneous injection; study drug was advanced to a dosage of 1.8 mg/d during the first 30 days as tolerated and continued for 180 days. MAIN OUTCOMES AND MEASURES The primary end point was a global rank score in which all patients, regardless of treatment assignment, were ranked across 3 hierarchical tiers: time to death, time to rehospitalization for heart failure, and time-averaged proportional change in N-terminal pro-B-type natriuretic peptide level from baseline to 180 days. Higher values indicate better health (stability). Exploratory secondary outcomes included primary end point components, cardiac structure and function, 6-minute walk distance, quality of life, and combined events. RESULTS Among the 300 patients who were randomized (median age, 61 years [interquartile range {IQR}, 52–68 years]; 64 [21%] women; 178 [59%] with type 2 diabetes; median LVEF of 25% [IQR, 19%–33%]; median N-terminal pro-B-type natriuretic peptide level of 2049 pg/mL [IQR, 1054–4235 pg/mL]), 271 completed the study. Compared with placebo, liraglutide had no significant effect on the primary end point (mean rank of 146 for the liraglutide group vs 156 for the

Clinical and Pharmaceutical Solutions through Analysis (CPSA BRASIL 2015): on the way to innovation - pharmaceutical/analytical technology, regulation and knowledge management.

PubMed

Needham, Shane; Yates, Nathan; Barrientos, Rafael; Steel, Martin; Lee, Mike

2015-12-01

Clinical and Pharmaceutical Solutions through Analysis, São Paulo, Brazil, 3-5 August 2015 The 2nd Annual Symposium on Clinical and Pharmaceutical Solutions through Analysis was held on 3-5 August 2015 at Club Transatlântico, São Paulo, Brazil. This annual meeting began in 2014 and was the first industry-led event in Brazil to focus on the specific needs of industry researchers while bringing together technology and regulators. The goal of CPSA is to provide an in-depth review of innovative technology and industry practices through open discussion of industry-related issues and needs. Education and specialized training are the foundation of all CPSA events. As the industry has evolved so has CPSA. The CPSA annual meeting thrived with high quality scientific content, open interaction from industry opinion leaders and a collegial environment.

Establishing a Multicenter Longitudinal Clinical Cohort Study in Ethiopia: Advanced Clinical Monitoring of Antiretroviral Treatment Project.

PubMed

Teklu, Alula M; Tsegaye, Eyuel; Fekade, Daniel; Hailemelak, Abraham; Weiss, William; Hassen, Elham; Simmons, Nicole; Zewdu, Solomon; Berhan, Yifru; Getachew, Assefa; Hagos, Tesfalem; Alebachew, Achamyeleh; Damena, Melake; Sitotaw, Yohannes; Assefa, Yibeltal; Medhin, Girmay; Ruff, Andrea

2017-02-01

The purpose of this paper is to describe the establishment of the Advanced Clinical Monitoring of ART Project in Ethiopia for monitoring and evaluation of the longitudinal effectiveness of the ART program and to show the opportunities it presents. This cohort was established in response to the 2005 call by WHO for establishing additional mechanisms for stronger monitoring of ART and the need for creating the platform to generate evidence to guide the care given for the ever increasing number of patients on ART in Ethiopia. A participatory and multi-stage process which started from a consensus building workshop and steered by a mother protocol as well as guiding documents which dictated the degree of engagement and expectations was followed. The primary and secondary aims of the study were agreed upon. A multi-site longitudinal observational clinical cohort was established by a consortium of stakeholders including seven Ethiopian medical schools and their affiliated referral hospitals, John Hopkins University, Ethiopian Public Health Institute, Ministry of Science and Technology, US Centers for Disease Prevention and Control - CDC-Ethiopia, and the Federal Ministry of Health. Adult and adolescent cohorts covering the age range of 14+ years) and pediatric cohorts covering those below age 14 years were the two main cohorts. During the initial recruitment of these cohorts information was extracted from existing documents for a total of 2,100 adult participants. In parallel, a prospective cohort of 1,400 adult and adolescent patients were enrolled for ART initiation and follow-up. Using similar recruitment procedures, a total of 120 children were enrolled in each of retrospective and prospective cohorts. Replacement of participants were made in subsequent years based on lost follow up and death rates to maintain adequacy of the sample to be followed-up. Between January 2005 and August 2013 a total of 4,339 patients were followed for a median of 41.6 months and data on

Simulation as a preoperative planning approach in advanced heart failure patients. A retrospective clinical analysis.

PubMed

Capoccia, Massimo; Marconi, Silvia; Singh, Sanjeet Avtaar; Pisanelli, Domenico M; De Lazzari, Claudio

2018-05-02

Modelling and simulation may become clinically applicable tools for detailed evaluation of the cardiovascular system and clinical decision-making to guide therapeutic intervention. Models based on pressure-volume relationship and zero-dimensional representation of the cardiovascular system may be a suitable choice given their simplicity and versatility. This approach has great potential for application in heart failure where the impact of left ventricular assist devices has played a significant role as a bridge to transplant and more recently as a long-term solution for non eligible candidates. We sought to investigate the value of simulation in the context of three heart failure patients with a view to predict or guide further management. CARDIOSIM © was the software used for this purpose. The study was based on retrospective analysis of haemodynamic data previously discussed at a multidisciplinary meeting. The outcome of the simulations addressed the value of a more quantitative approach in the clinical decision process. Although previous experience, co-morbidities and the risk of potentially fatal complications play a role in clinical decision-making, patient-specific modelling may become a daily approach for selection and optimisation of device-based treatment for heart failure patients. Willingness to adopt this integrated approach may be the key to further progress.

Rasmussen’s encephalitis: clinical features, pathobiology, and treatment advances

PubMed Central

Varadkar, Sophia; Bien, Christian G; Kruse, Carol A; Jensen, Frances E; Bauer, Jan; Pardo, Carlos A; Vincent, Angela; Mathern, Gary W; Cross, J Helen

2014-01-01

Rasmussen’s encephalitis is a rare chronic neurological disorder, characterised by unilateral inflammation of the cerebral cortex, drug-resistant epilepsy, and progressive neurological and cognitive deterioration. Neuropathological and immunological studies support the notion that Rasmussen’s encephalitis is probably driven by a T-cell response to one or more antigenic epitopes, with potential additional contribution by autoantibodies. Careful analysis of the association between histopathology and clinical presentation suggests that initial damage to the brain is mediated by T cells and microglia, suggesting a window for treatment if Rasmussen’s encephalitis can be diagnosed early. Advances in neuroimaging suggest that progression of the inflammatory process seen with MRI might be a good biomarker in Rasmussen’s encephalitis. For many patients, families, and doctors, choosing the right time to move from medical management to surgery is a real therapeutic dilemma. Cerebral hemispherectomy remains the only cure for seizures, but there are inevitable functional compromises. Decisions of whether or when surgery should be undertaken are challenging in the absence of a dense neurological deficit, and vary by institutional experience. Further, the optimum time for surgery, to give the best language and cognitive outcome, is not yet well understood. Immunomodulatory treatments seem to slow rather than halt disease progression in Rasmussen’s encephalitis, without changing the eventual outcome. PMID:24457189

Current advances and future perspectives in extrusion-based bioprinting.

PubMed

Ozbolat, Ibrahim T; Hospodiuk, Monika

2016-01-01

Extrusion-based bioprinting (EBB) is a rapidly growing technology that has made substantial progress during the last decade. It has great versatility in printing various biologics, including cells, tissues, tissue constructs, organ modules and microfluidic devices, in applications from basic research and pharmaceutics to clinics. Despite the great benefits and flexibility in printing a wide range of bioinks, including tissue spheroids, tissue strands, cell pellets, decellularized matrix components, micro-carriers and cell-laden hydrogels, the technology currently faces several limitations and challenges. These include impediments to organ fabrication, the limited resolution of printed features, the need for advanced bioprinting solutions to transition the technology bench to bedside, the necessity of new bioink development for rapid, safe and sustainable delivery of cells in a biomimetically organized microenvironment, and regulatory concerns to transform the technology into a product. This paper, presenting a first-time comprehensive review of EBB, discusses the current advancements in EBB technology and highlights future directions to transform the technology to generate viable end products for tissue engineering and regenerative medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Utilising the Intel RealSense Camera for Measuring Health Outcomes in Clinical Research.

PubMed

Siena, Francesco Luke; Byrom, Bill; Watts, Paul; Breedon, Philip

2018-02-05

Applications utilising 3D Camera technologies for the measurement of health outcomes in the health and wellness sector continues to expand. The Intel® RealSense™ is one of the leading 3D depth sensing cameras currently available on the market and aligns itself for use in many applications, including robotics, automation, and medical systems. One of the most prominent areas is the production of interactive solutions for rehabilitation which includes gait analysis and facial tracking. Advancements in depth camera technology has resulted in a noticeable increase in the integration of these technologies into portable platforms, suggesting significant future potential for pervasive in-clinic and field based health assessment solutions. This paper reviews the Intel RealSense technology's technical capabilities and discusses its application to clinical research and includes examples where the Intel RealSense camera range has been used for the measurement of health outcomes. This review supports the use of the technology to develop robust, objective movement and mobility-based endpoints to enable accurate tracking of the effects of treatment interventions in clinical trials.

Advanced material and approach for metal ions removal from aqueous solutions

PubMed Central

Turhanen, Petri A.; Vepsäläinen, Jouko J.; Peräniemi, Sirpa

2015-01-01

A Novel approach to remove metals from aqueous solutions has been developed. The method is based on a resin free, solid, non-toxic, microcrystalline bisphosphonate material, which has very low solubility in water (59 mg/l to ion free Milli-Q water and 13 mg/l to 3.5% NaCl solution). The material has been produced almost quantitatively on a 1 kg scale (it has been prepared also on a pilot scale, ca. 7 kg) and tested successfully for its ability to collect metal cations from different sources, such as ground water and mining process waters. Not only was this material highly efficient at collecting several metal ions out of solution it also proved to be regenerable and reusable over a number of adsorption/desorption, which is crucial for environmental friendliness. This material has several advantages compared to the currently used approaches, such as no need for any precipitation step. PMID:25758924

An innovative solution to raise public awareness using a mobile colorectal clinic - The 'bowel bus'.

PubMed

Naguib, N; Lewis, M; Iredale, R; Pugh, R; Haray, P N

2017-03-01

Colorectal cancer is the fourth most common cancer in the United Kingdom; however, figures show that the uptake for bowel cancer screening lags behind other cancer screening programmes. This is a report of a multi-staged development of an outreach colorectal clinical community service provided through a Mobile Unit (a Bowel Bus). The unit delivers a one-stop colorectal clinic that provides a rapid access pathway to members of the public who have concerns about, or symptoms of, bowel cancer. The aims of the project were to increase public awareness about colorectal cancer and to provide an outreach clinic as a supplement to the hospital based colorectal clinic. This service is a result of collaborative efforts between Tenovus Cancer Care (TCC) and the colorectal surgery department of the local NHS Hospital. During one year, the Bowel Bus has provided services to 772 members of the local community. 244 patients were examined by the colorectal nurse specialist including 66 drop-in patients and 135 patients referred by the GPs. The service led to decrease in the waiting list for routine referrals to be seen in the colorectal clinic at the hospital from a mean of 10.5 weeks-5.9 weeks. A feedback questionnaire from 180 patients, used to audit the quality of the service, has confirmed an overwhelming satisfaction with the service. The Mobile Unit is a novel solution to addressing the ever increasing demand for specialist outpatient services without compromising the quality of care whilst enhancing the patient experience. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Irrigation of Abdomen With Imipenem Solution Decreases Surgical Site Infections in Patients With Perforated Appendicitis: A Randomized Clinical Trial

PubMed Central

Hesami, Mohammad Ali; Alipour, Hamid; Nikoupour Daylami, Hamed; Alipour, Bijan; Bazargan-Hejazi, Shahrzad; Ahmadi, Alireza

2014-01-01

Background: Perforated appendicitis is one of the most common causes of acute abdomen requiring emergent surgery for immediate appendectomy and peritoneal cavity irrigation; however, the efficacy of irrigation with antibiotic solutions is controversial. Objectives: The aim of this study was to assess the efficacy of imipenem solution irrigation on post-operative surgical site infections (SSIs), hospital length of stay, and hospital costs. We hypothesized that there would be lower rate of SSIs, a shorter hospital stay, and lower hospital cost in patients with perforated appendicitis who received peritoneal cavity irrigation with imipenem solution in comparison to their counterparts who received irrigation with normal saline. Patients and Methods: In this randomized single-blind parallel-group clinical trial, we enrolled 90 patients with perforated appendicitis with 12-50 years of age and randomly allocated them into experimental group (n = 45) and control group (n = 45). The control group received peritoneal irrigation with normal saline (0.9%) and experimental group underwent peritoneal irrigation with imipenem solution (1 mg/mL). All surgical procedures were performed in Imam Reza Hospital of Kermanshah University of Medical Sciences. The study primary outcome was surgical site infections (including wound infection and abdominal abscess) and the secondary outcomes were length of hospital stay and hospital cost. Chi-squared and t-tests were used to analyze the study data. Results: Imipenem solution irrigation was associated with significant clinical improvement at one-month follow-up. The experimental group presented with significantly lower rate of SSIs and shorter length of hospital stay. The experimental group had lower rate of SSIs compared to the control group (4.4% vs. 22.2%, respectively) (p= 0.013). The duration of hospital stay was nearly one day longer in control group (5.84 ± 2.58 days) vs. experimental group (4.91 ± 1.29 days) (P = 0.034), and

A regulatory perspective of clinical trial applications for biological products with particular emphasis on Advanced Therapy Medicinal Products (ATMPs)

PubMed Central

Jones, David R; McBlane, James W; McNaughton, Graham; Rajakumaraswamy, Nishanthan; Wydenbach, Kirsty

2013-01-01

The safety of trial subjects is the tenet that guides the regulatory assessment of a Clinical Trial Authorization application and applies equally to trials involving small molecules and those with biological/biotechnological products, including Advanced Therapy Medicinal Products. The objective of a regulator is to ensure that the potential risk faced by a trial subject is outweighed by the potential benefit to them from taking part in the trial. The focus of the application review is to assess whether risks have been identified and appropriate steps taken to alleviate these as much as possible. Other factors are also taken into account during a review, such as regulatory requirements, and emerging non-clinical and clinical data from other trials on the same or similar products. This paper examines the regulatory review process of a Clinical Trial Authorization application from the perspectives of Quality, Non-Clinical and Clinical Regulatory Assessors at the Medicines and Healthcare products Regulatory Agency. It should be noted that each perspective has highlighted specific issues from their individual competence and that these can be different between the disciplines. PMID:23216470

Applications of the MapReduce programming framework to clinical big data analysis: current landscape and future trends

PubMed Central

2014-01-01

The emergence of massive datasets in a clinical setting presents both challenges and opportunities in data storage and analysis. This so called “big data” challenges traditional analytic tools and will increasingly require novel solutions adapted from other fields. Advances in information and communication technology present the most viable solutions to big data analysis in terms of efficiency and scalability. It is vital those big data solutions are multithreaded and that data access approaches be precisely tailored to large volumes of semi-structured/unstructured data. The MapReduce programming framework uses two tasks common in functional programming: Map and Reduce. MapReduce is a new parallel processing framework and Hadoop is its open-source implementation on a single computing node or on clusters. Compared with existing parallel processing paradigms (e.g. grid computing and graphical processing unit (GPU)), MapReduce and Hadoop have two advantages: 1) fault-tolerant storage resulting in reliable data processing by replicating the computing tasks, and cloning the data chunks on different computing nodes across the computing cluster; 2) high-throughput data processing via a batch processing framework and the Hadoop distributed file system (HDFS). Data are stored in the HDFS and made available to the slave nodes for computation. In this paper, we review the existing applications of the MapReduce programming framework and its implementation platform Hadoop in clinical big data and related medical health informatics fields. The usage of MapReduce and Hadoop on a distributed system represents a significant advance in clinical big data processing and utilization, and opens up new opportunities in the emerging era of big data analytics. The objective of this paper is to summarize the state-of-the-art efforts in clinical big data analytics and highlight what might be needed to enhance the outcomes of clinical big data analytics tools. This paper is concluded by

Applications of the MapReduce programming framework to clinical big data analysis: current landscape and future trends.

PubMed

Mohammed, Emad A; Far, Behrouz H; Naugler, Christopher

2014-01-01

The emergence of massive datasets in a clinical setting presents both challenges and opportunities in data storage and analysis. This so called "big data" challenges traditional analytic tools and will increasingly require novel solutions adapted from other fields. Advances in information and communication technology present the most viable solutions to big data analysis in terms of efficiency and scalability. It is vital those big data solutions are multithreaded and that data access approaches be precisely tailored to large volumes of semi-structured/unstructured data. THE MAPREDUCE PROGRAMMING FRAMEWORK USES TWO TASKS COMMON IN FUNCTIONAL PROGRAMMING: Map and Reduce. MapReduce is a new parallel processing framework and Hadoop is its open-source implementation on a single computing node or on clusters. Compared with existing parallel processing paradigms (e.g. grid computing and graphical processing unit (GPU)), MapReduce and Hadoop have two advantages: 1) fault-tolerant storage resulting in reliable data processing by replicating the computing tasks, and cloning the data chunks on different computing nodes across the computing cluster; 2) high-throughput data processing via a batch processing framework and the Hadoop distributed file system (HDFS). Data are stored in the HDFS and made available to the slave nodes for computation. In this paper, we review the existing applications of the MapReduce programming framework and its implementation platform Hadoop in clinical big data and related medical health informatics fields. The usage of MapReduce and Hadoop on a distributed system represents a significant advance in clinical big data processing and utilization, and opens up new opportunities in the emerging era of big data analytics. The objective of this paper is to summarize the state-of-the-art efforts in clinical big data analytics and highlight what might be needed to enhance the outcomes of clinical big data analytics tools. This paper is concluded by

W(h)ither human cardiac and body magnetic resonance at ultrahigh fields? technical advances, practical considerations, applications, and clinical opportunities.

PubMed

Niendorf, Thoralf; Paul, Katharina; Oezerdem, Celal; Graessl, Andreas; Klix, Sabrina; Huelnhagen, Till; Hezel, Fabian; Rieger, Jan; Waiczies, Helmar; Frahm, Jens; Nagel, Armin M; Oberacker, Eva; Winter, Lukas

2016-09-01

The objective of this study was to document and review advances and groundbreaking progress in cardiac and body MR at ultrahigh fields (UHF, B0 ≥ 7.0 T) with the goal to attract talent, clinical adopters, collaborations and resources to the biomedical and diagnostic imaging communities. This review surveys traits, advantages and challenges of cardiac and body MR at 7.0 T. The considerations run the gamut from technical advances to clinical opportunities. Key concepts, emerging technologies, practical considerations, frontier applications and future directions of UHF body and cardiac MR are provided. Examples of UHF cardiac and body imaging strategies are demonstrated. Their added value over the kindred counterparts at lower fields is explored along with an outline of research promises. The achievements of cardiac and body UHF-MR are powerful motivators and enablers, since extra speed, signal and imaging capabilities may be invested to overcome the fundamental constraints that continue to hamper traditional cardiac and body MR applications. If practical obstacles, concomitant physics effects and technical impediments can be overcome in equal measure, sophisticated cardiac and body UHF-MR will help to open the door to new MRI and MRS approaches for basic research and clinical science, with the lessons learned at 7.0 T being transferred into broad clinical use including diagnostics and therapy guiding at lower fields. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Methodology of health-related quality of life analysis in phase III advanced non-small-cell lung cancer clinical trials: a critical review.

PubMed

Fiteni, Frédéric; Anota, Amélie; Westeel, Virginie; Bonnetain, Franck

2016-02-18

Health-related quality of life (HRQoL) is recognized as a component endpoint for cancer therapy approvals. The aim of this review was to evaluate the methodology of HRQoL analysis and reporting in phase III clinical trials of first-line chemotherapy in advanced non-small cell lung cancers (NSCLC). A search in MEDLINE databases identified phase III clinical trials in first-line chemotherapy for advanced NSCLC, published between January 2008 to December 2014. Two authors independently extracted information using predefined data abstraction forms. A total of 55 phase III advanced NSCLC trials were identified. HRQoL was declared as an endpoint in 27 studies (49%). Among these 27 studies, The EORTC questionnaire Quality of Life Questionnaire C30 was used in 13 (48%) of the studies and The Functional Assessment of Cancer Therapy-General was used in 12 (44%) trials. The targeted dimensions of HRQoL, the minimal clinically important difference and the statistical approaches for dealing with missing data were clearly specified in 13 (48.1%), 9 (33.3%) and 5 (18.5%) studies, respectively. The most frequent statistical methods for HRQoL analysis were: the mean change from baseline (33.3%), the linear mixed model for repeated measures (22.2%) and time to HRQoL score deterioration (18.5%). For each targeted dimension, the results for each group, the estimated effect size and its precision were clearly reported in 4 studies (14.8%), not clearly reported in 11 studies (40.7%) and not reported at all in 12 studies (44.4%). This review demonstrated the weakness and the heterogeneity of the measurement, analysis, and reporting of HRQoL in phase III advanced NSCLC trials. Precise and uniform recommendations are needed to compare HRQoL results across publications and to provide understandable messages for patients and clinicians.

Circulating tumor cells: advances in isolation and analysis, and challenges for clinical applications

PubMed Central

Harouaka, Ramdane; Kang, Zhigang; Zheng, Siyang; Cao, Liang

2013-01-01

Circulating tumor cells (CTCs) are rare cancer cells released from tumors into the bloodstream that are thought to have a key role in cancer metastasis. The presence of CTCs has been associated with worse prognosis in several major cancer types, including breast, prostate and colorectal cancer. There is considerable interest in CTC research and technologies for their potential use as cancer biomarkers that may enhance cancer diagnosis and prognosis, facilitate drug development, and improve the treatment of cancer patients. This review provides an update on recent progress in CTC isolation and molecular characterization technologies. Furthermore, the review covers significant advances and limitations in the clinical applications of CTC-based assays for cancer prognosis, response to anti-cancer therapies, and exploratory studies in biomarkers predictive of sensitivity and resistance to cancer therapies. PMID:24134902

Circulating tumor cells: advances in isolation and analysis, and challenges for clinical applications.

PubMed

Harouaka, Ramdane; Kang, Zhigang; Zheng, Si-Yang; Cao, Liang

2014-02-01

Circulating tumor cells (CTCs) are rare cancer cells released from tumors into the bloodstream that are thought to have a key role in cancer metastasis. The presence of CTCs has been associated with worse prognosis in several major cancer types, including breast, prostate and colorectal cancer. There is considerable interest in CTC research and technologies for their potential use as cancer biomarkers that may enhance cancer diagnosis and prognosis, facilitate drug development, and improve the treatment of cancer patients. This review provides an update on recent progress in CTC isolation and molecular characterization technologies. Furthermore, the review covers significant advances and limitations in the clinical applications of CTC-based assays for cancer prognosis, response to anti-cancer therapies, and exploratory studies in biomarkers predictive of sensitivity and resistance to cancer therapies. Published by Elsevier Inc.

Advanced marketing: how to protect and advance your practice.

PubMed

Lexa, Frank James

2007-02-01

Radiology practices in the United States are facing mounting competitive challenges in many metropolitan areas. This competition is multifaceted and includes other traditional diagnostic imagers. However, the most severe pressures are from new entrants, such as primary and specialty physicians outside of radiology. The business science of marketing provides a set of solutions to help you fight back against this onslaught. In particular, advanced marketing techniques offer compelling strengths for raising awareness of the unique nature of our specialty among both the lay population and primary referrers. Applications of advanced marketing can be used to simultaneously hold and expand your turf. Relying on smarts rather than dollars, they also help overcome the fears that many radiology practices have about the high costs of traditional broadcasting.

Processing of solid solution, mixed uranium/refractory metal carbides for advanced space nuclear power and propulsion systems

NASA Astrophysics Data System (ADS)

Knight, Travis Warren

Nuclear thermal propulsion (NTP) and space nuclear power are two enabling technologies for the manned exploration of space and the development of research outposts in space and on other planets such as Mars. Advanced carbide nuclear fuels have been proposed for application in space nuclear power and propulsion systems. This study examined the processing technologies and optimal parameters necessary to fabricate samples of single phase, solid solution, mixed uranium/refractory metal carbides. In particular, the pseudo-ternary carbide, UC-ZrC-NbC, system was examined with uranium metal mole fractions of 5% and 10% and corresponding uranium densities of 0.8 to 1.8 gU/cc. Efforts were directed to those methods that could produce simple geometry fuel elements or wafers such as those used to fabricate a Square Lattice Honeycomb (SLHC) fuel element and reactor core. Methods of cold uniaxial pressing, sintering by induction heating, and hot pressing by self-resistance heating were investigated. Solid solution, high density (low porosity) samples greater than 95% TD were processed by cold pressing at 150 MPa and sintering above 2600 K for times longer than 90 min. Some impurity oxide phases were noted in some samples attributed to residual gases in the furnace during processing. Also, some samples noted secondary phases of carbon and UC2 due to some hyperstoichiometric powder mixtures having carbon-to-metal ratios greater than one. In all, 33 mixed carbide samples were processed and analyzed with half bearing uranium as ternary carbides of UC-ZrC-NbC. Scanning electron microscopy, x-ray diffraction, and density measurements were used to characterize samples. Samples were processed from powders of the refractory mono-carbides and UC/UC 2 or from powders of uranium hydride (UH3), graphite, and refractory metal carbides to produce hypostoichiometric mixed carbides. Samples processed from the constituent carbide powders and sintered at temperatures above the melting point of UC

Advanced medical imaging protocol workflow-a flexible electronic solution to optimize process efficiency, care quality and patient safety in the National VA Enterprise.

PubMed

Medverd, Jonathan R; Cross, Nathan M; Font, Frank; Casertano, Andrew

2013-08-01

Radiologists routinely make decisions with only limited information when assigning protocol instructions for the performance of advanced medical imaging examinations. Opportunity exists to simultaneously improve the safety, quality and efficiency of this workflow through the application of an electronic solution leveraging health system resources to provide concise, tailored information and decision support in real-time. Such a system has been developed using an open source, open standards design for use within the Veterans Health Administration. The Radiology Protocol Tool Recorder (RAPTOR) project identified key process attributes as well as inherent weaknesses of paper processes and electronic emulators of paper processes to guide the development of its optimized electronic solution. The design provides a kernel that can be expanded to create an integrated radiology environment. RAPTOR has implications relevant to the greater health care community, and serves as a case model for modernization of legacy government health information systems.

Point-of-Care Technologies for Precision Cardiovascular Care and Clinical Research

PubMed Central

King, Kevin; Grazette, Luanda P.; Paltoo, Dina N.; McDevitt, John T.; Sia, Samuel K.; Barrett, Paddy M.; Apple, Fred S.; Gurbel, Paul A.; Weissleder, Ralph; Leeds, Hilary; Iturriaga, Erin J.; Rao, Anupama; Adhikari, Bishow; Desvigne-Nickens, Patrice; Galis, Zorina S.; Libby, Peter

2016-01-01

Point-of-care technologies (POC or POCT) are enabling innovative cardiovascular diagnostics that promise to improve patient care across diverse clinical settings. The National Heart, Lung, and Blood Institute convened a working group to discuss POCT in cardiovascular medicine. The multidisciplinary working group, which included clinicians, scientists, engineers, device manufacturers, regulatory officials, and program staff, reviewed the state of the POCT field; discussed opportunities for POCT to improve cardiovascular care, realize the promise of precision medicine, and advance the clinical research enterprise; and identified barriers facing translation and integration of POCT with existing clinical systems. A POCT development roadmap emerged to guide multidisciplinary teams of biomarker scientists, technologists, health care providers, and clinical trialists as they: 1) formulate needs assessments; 2) define device design specifications; 3) develop component technologies and integrated systems; 4) perform iterative pilot testing; and 5) conduct rigorous prospective clinical testing to ensure that POCT solutions have substantial effects on cardiovascular care. PMID:26977455

From orphan drugs to adopted therapies: Advancing C3-targeted intervention to the clinical stage

PubMed Central

Mastellos, Dimitrios C.; Reis, Edimara S.; Yancopoulou, Despina; Hajishengallis, George; Ricklin, Daniel; Lambris, John D.

2016-01-01

Complement dysregulation is increasingly recognized as an important pathogenic driver in a number of clinical disorders. Complement-triggered pathways intertwine with key inflammatory and tissue destructive processes that can either increase the risk of disease or exacerbate pathology in acute or chronic conditions. The launch of the first complement-targeted drugs in the clinic has undeniably stirred the field of complement therapeutic design, providing new insights into complement's contribution to disease pathogenesis and also helping to leverage a more personalized, comprehensive approach to patient management. In this regard, a rapidly expanding toolbox of complement therapeutics is being developed to address unmet clinical needs in several immune-mediated and inflammatory diseases. Elegant approaches employing both surface-directed and fluid-phase inhibitors have exploited diverse components of the complement cascade as putative points of therapeutic intervention. Targeting C3, the central hub of the system, has proven to be a promising strategy for developing biologics as well as small-molecule inhibitors with clinical potential. Complement modulation at the level of C3 has recently shown promise in preclinical primate models, opening up new avenues for therapeutic intervention in both acute and chronic indications fueled by uncontrolled C3 turnover. This review highlights recent developments in the field of complement therapeutics, focusing on C3-directed inhibitors and alternative pathway (AP) regulator-based approaches. Translational perspectives and considerations are discussed, particularly with regard to the structure-guided drug optimization and clinical advancement of a new generation of C3-targeted peptidic inhibitors. PMID:27353192

Analysis of clinically important factors on the performance of advanced hydraulic, microprocessor-controlled exo-prosthetic knee joints based on 899 trial fittings.

PubMed

Hahn, Andreas; Lang, Michael; Stuckart, Claudia

2016-11-01

The objective of this work is to evaluate whether clinically important factors may predict an individual's capability to utilize the functional benefits provided by an advanced hydraulic, microprocessor-controlled exo-prosthetic knee component.This retrospective cross-sectional cohort analysis investigated the data of above knee amputees captured during routine trial fittings. Prosthetists rated the performance indicators showing the functional benefits of the advanced maneuvering capabilities of the device. Subjects were asked to rate their perception. Simple and multiple linear and logistic regression was applied.Data from 899 subjects with demographics typical for the population were evaluated. Ability to vary gait speed, perform toileting, and ascend stairs were identified as the most sensitive performance predictors. Prior C-Leg users showed benefits during advanced maneuvering. Variables showed plausible and meaningful effects, however, could not claim predictive power. Mobility grade showed the largest effect but also failed to be predictive.Clinical parameters such as etiology, age, mobility grade, and others analyzed here do not suffice to predict individual potential. Daily walking distance may pose a threshold value and be part of a predictive instrument. Decisions based solely on single parameters such as mobility grade rating or walking distance seem to be questionable.

A Generalized Deduction of the Ideal-Solution Model

ERIC Educational Resources Information Center

Leo, Teresa J.; Perez-del-Notario, Pedro; Raso, Miguel A.

2006-01-01

A new general procedure for deriving the Gibbs energy of mixing is developed through general thermodynamic considerations, and the ideal-solution model is obtained as a special particular case of the general one. The deduction of the Gibbs energy of mixing for the ideal-solution model is a rational one and viewed suitable for advanced students who…

Comprehensive genomic profiling of 295 cases of clinically advanced urothelial carcinoma of the urinary bladder reveals a high frequency of clinically relevant genomic alterations.

PubMed

Ross, Jeffrey S; Wang, Kai; Khaira, Depinder; Ali, Siraj M; Fisher, Huge A G; Mian, Badar; Nazeer, Tipu; Elvin, Julia A; Palma, Norma; Yelensky, Roman; Lipson, Doron; Miller, Vincent A; Stephens, Philip J; Subbiah, Vivek; Pal, Sumanta K

2016-03-01

In the current study, the authors present a comprehensive genomic profile (CGP)-based study of advanced urothelial carcinoma (UC) designed to detect clinically relevant genomic alterations (CRGAs). DNA was extracted from 40 µm of formalin-fixed, paraffin-embedded sections from 295 consecutive cases of recurrent/metastatic UC. CGP was performed on hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of 688X for all coding exons of 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer, using process-matched normal control samples as a reference. CRGAs were defined as GAs linked to drugs on the market or currently under evaluation in mechanism-driven clinical trials. All 295 patients assessed were classified with high-grade (International Society of Urological Pathology classification) and advanced stage (stage III/IV American Joint Committee on Cancer) disease, and 294 of 295 patients (99.7%) had at least 1 GA on CGP with a mean of 6.4 GAs per UC (61% substitutions/insertions/deletions, 37% copy number alterations, and 2% fusions). Furthermore, 275 patients (93%) had at least 1 CRGA involving 75 individual genes with a mean of 2.6 CRGAs per UC. The most common CRGAs involved cyclin-dependent kinase inhibitor 2A (CDKN2A) (34%), fibroblast growth factor receptor 3 (FGFR3) (21%), phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) (20%), and ERBB2 (17%). FGFR3 GAs were diverse types and included 10% fusions. ERBB2 GAs were equally divided between amplifications and substitutions. ERBB2 substitutions were predominantly within the extracellular domain and were highly enriched in patients with micropapillary UC (38% of 32 cases vs 5% of 263 nonmicropapillary UC cases; P<.0001). Using a CGP assay capable of detecting all classes of GA simultaneously, an extraordinarily high frequency of CRGA was identified in a large series of patients with advanced UC. Cancer 2016;122:702-711. © 2015 American

National Institute of Biomedical Imaging and Bioengineering Point-of-Care Technology Research Network: Advancing Precision Medicine

PubMed Central

Ford Carleton, Penny; Parrish, John A.; Collins, John M.; Crocker, J. Benjamin; Dixon, Ronald F.; Edgman-Levitan, Susan; Lewandrowski, Kent B.; Stahl, James E.; Klapperich, Catherine; Cabodi, Mario; Gaydos, Charlotte A.; Rompalo, Anne M.; Manabe, Yukari; Wang, Tza-Huei; Rothman, Richard; Geddes, Chris D.; Widdice, Lea; Jackman, Joany; Mathura, Rishi A.; Lash, Tiffani Bailey

2016-01-01

To advance the development of point-of-care technology (POCT), the National Institute of Biomedical Imaging and Bioengineering established the POCT Research Network (POCTRN), comprised of Centers that emphasize multidisciplinary partnerships and close facilitation to move technologies from an early stage of development into clinical testing and patient use. This paper describes the POCTRN and the three currently funded Centers as examples of academic-based organizations that support collaborations across disciplines, institutions, and geographic regions to successfully drive innovative solutions from concept to patient care. PMID:27730014

Some Solutions for Successful Aging.

ERIC Educational Resources Information Center

Demery, Marie

America is rapidly becoming an aging society. This phenomenon is supported by statistics and fueled by socioeconomic developments, medical advances, and the probability of continued lower fertility. Seven themes provide some solutions for the successful process of aging: (1) "Vital Involvement" stresses interactions that are important to the…

A clinical ladder for occupational health nurses.

PubMed

Lang, Yolanda C

2010-06-01

Occupational health nurses must have a growing, expanding knowledge base to remain current in practice. The American Board for Occupational Health Nurses, Inc. encourages advancement with the availability of certification examinations. Health care centers support clinical advancement programs for bedside nurses. Nurses who continue their education either through a degree program or via continuing education or certification advance up the clinical ladder, receiving a higher salary, recognition from their peers, and perhaps even financial assistance to continue climbing, yet occupational health nurses do not have their own clinical advancement ladder. This article examines the steps necessary to develop a clinical ladder and presents a clinical ladder specific to occupational health nursing developed by the author. Copyright 2010, SLACK Incorporated.

The fractal heart — embracing mathematics in the cardiology clinic

PubMed Central

Captur, Gabriella; Karperien, Audrey L.; Hughes, Alun D.; Francis, Darrel P.; Moon, James C.

2017-01-01

For clinicians grappling with quantifying the complex spatial and temporal patterns of cardiac structure and function (such as myocardial trabeculae, coronary microvascular anatomy, tissue perfusion, myocyte histology, electrical conduction, heart rate, and blood-pressure variability), fractal analysis is a powerful, but still underused, mathematical tool. In this Perspectives article, we explain some fundamental principles of fractal geometry and place it in a familiar medical setting. We summarize studies in the cardiovascular sciences in which fractal methods have successfully been used to investigate disease mechanisms, and suggest potential future clinical roles in cardiac imaging and time series measurements. We believe that clinical researchers can deploy innovative fractal solutions to common cardiac problems that might ultimately translate into advancements for patient care. PMID:27708281

The association of contact lens solution use and Acanthamoeba keratitis.

PubMed

Joslin, Charlotte E; Tu, Elmer Y; Shoff, Megan E; Booton, Gregory C; Fuerst, Paul A; McMahon, Timothy T; Anderson, Robert J; Dworkin, Mark S; Sugar, Joel; Davis, Faith G; Stayner, Leslie T

2007-08-01

To investigate Acanthamoeba keratitis (AK) risk factors. Diagnosis of AK, a rare but serious corneal infection, has recently increased significantly at the University of Illinois at Chicago (UIC) Cornea Service. Retrospective case-control study. settings: University, tertiary care hospital. patients: Fifty-five AK cases with contact lens use were diagnosed between May 1, 2003 and September 15, 2006. Clinic-matched controls with contact lens use were recruited. Subjects completed surveys targeting lens hygiene, contact lens solution use, and water exposure. main outcome measure: Acanthamoeba keratitis. Thirty-nine (73.6%) cases and 113 (65.3%) controls participated; 38 cases had complete contact lens data. Thirty-five of 38 cases (92.1%) and 47 of 100 controls (47.0%) used soft lenses. Analysis was performed on 30 cases and 39 controls with matched pairs with soft lens use. Exclusive use of Advance Medical Optics (AMO) Complete MoisturePlus Multi-Purpose Solution was independently associated with AK in multivariable analysis (55.2% vs 10.5%; odds ratio [OR], 16.67; 95% confidence interval [CI] 2.11 to 162.63; P = .008). However, 38.8% of cases reported no use of AMO Complete MoisturePlus Multi-Purpose Solution either alone or in combination with other solutions. Although not statistically significant, additional hygiene-related variables (solution "reuse," lack of "rubbing," and showering with lenses) suggest a pattern of risk. AMO Complete MoisturePlus Multi-Purpose Solution use is independently associated with AK among soft contact lens users. However, it does not explain all cases, suggesting additional factors. Further research into environmental risk factors and hygiene practices is warranted, especially considering this is the second outbreak of an atypical, contact lens-related infection.

A randomized, controlled trial of in situ pediatric advanced life support recertification ("pediatric advanced life support reconstructed") compared with standard pediatric advanced life support recertification for ICU frontline providers*.

PubMed

Kurosawa, Hiroshi; Ikeyama, Takanari; Achuff, Patricia; Perkel, Madeline; Watson, Christine; Monachino, Annemarie; Remy, Daphne; Deutsch, Ellen; Buchanan, Newton; Anderson, Jodee; Berg, Robert A; Nadkarni, Vinay M; Nishisaki, Akira

2014-03-01

Recent evidence shows poor retention of Pediatric Advanced Life Support provider skills. Frequent refresher training and in situ simulation are promising interventions. We developed a "Pediatric Advanced Life Support-reconstructed" recertification course by deconstructing the training into six 30-minute in situ simulation scenario sessions delivered over 6 months. We hypothesized that in situ Pediatric Advanced Life Support-reconstructed implementation is feasible and as effective as standard Pediatric Advanced Life Support recertification. A prospective randomized, single-blinded trial. Single-center, large, tertiary PICU in a university-affiliated children's hospital. Nurses and respiratory therapists in PICU. Simulation-based modular Pediatric Advanced Life Support recertification training. Simulation-based pre- and postassessment sessions were conducted to evaluate participants' performance. Video-recorded sessions were rated by trained raters blinded to allocation. The primary outcome was skill performance measured by a validated Clinical Performance Tool, and secondary outcome was behavioral performance measured by a Behavioral Assessment Tool. A mixed-effect model was used to account for baseline differences. Forty participants were prospectively randomized to Pediatric Advanced Life Support reconstructed versus standard Pediatric Advanced Life Support with no significant difference in demographics. Clinical Performance Tool score was similar at baseline in both groups and improved after Pediatric Advanced Life Support reconstructed (pre, 16.3 ± 4.1 vs post, 22.4 ± 3.9; p < 0.001), but not after standard Pediatric Advanced Life Support (pre, 14.3 ± 4.7 vs post, 14.9 ± 4.4; p =0.59). Improvement of Clinical Performance Tool was significantly higher in Pediatric Advanced Life Support reconstructed compared with standard Pediatric Advanced Life Support (p = 0.006). Behavioral Assessment Tool improved in both groups: Pediatric Advanced Life Support

Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline.

PubMed

Ramakrishna, Naren; Temin, Sarah; Chandarlapaty, Sarat; Crews, Jennie R; Davidson, Nancy E; Esteva, Francisco J; Giordano, Sharon H; Gonzalez-Angulo, Ana M; Kirshner, Jeffrey J; Krop, Ian; Levinson, Jennifer; Modi, Shanu; Patt, Debra A; Perez, Edith A; Perlmutter, Jane; Winer, Eric P; Lin, Nancy U

2014-07-01

To provide formal expert consensus-based recommendations to practicing oncologists and others on the management of brain metastases for patients with human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer. The American Society of Clinical Oncology (ASCO) convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts and conducted a systematic review of the literature. When that failed to yield sufficiently strong quality evidence, the Expert Panel undertook a formal expert consensus-based process to produce these recommendations. ASCO used a modified Delphi process. The panel members drafted recommendations, and a group of other experts joined them for two rounds of formal ratings of the recommendations. No studies or existing guidelines met the systematic review criteria; therefore, ASCO conducted a formal expert consensus-based process. Patients with brain metastases should receive appropriate local therapy and systemic therapy, if indicated. Local therapies include surgery, whole-brain radiotherapy, and stereotactic radiosurgery. Treatments depend on factors such as patient prognosis, presence of symptoms, resectability, number and size of metastases, prior therapy, and whether metastases are diffuse. Other options include systemic therapy, best supportive care, enrollment onto a clinical trial, and/or palliative care. Clinicians should not perform routine magnetic resonance imaging (MRI) to screen for brain metastases, but rather should have a low threshold for MRI of the brain because of the high incidence of brain metastases among patients with HER2-positive advanced breast cancer. © 2014 by American Society of Clinical Oncology.

Technological advances in radiotherapy for cervical cancer.

PubMed

Walsh, Lorraine; Morgia, Marita; Fyles, Anthony; Milosevic, Michael

2011-09-01

To discuss the important technological advances that have taken place in the planning and delivery of both external beam radiotherapy and brachytherapy for patients with locally advanced cervical cancer, and the implications for improved clinical outcomes. Technological advances in external beam radiation treatment and brachytherapy for patients with cervical cancer allow more precise targeting of tumour and relative sparing of surrounding normal organs and tissues. Early evidence is emerging to indicate that these advances will translate into improvements in tumour control and reduced side effects. However, there are patient, tumour and treatment-related factors that can detract from these benefits. Foremost among these is complex, unpredictable and sometimes dramatic internal tumour and normal organ motion during treatment. The focus of current research and clinical development is on tracking internal anatomic change in individual patients and adapting treatment plans as required to assure that optimal tumour coverage and normal tissue sparing is maintained at all times. The success of this approach will depend on clear definitions of target volumes, high resolution daily soft tissue imaging, and new software tools for rapid contouring, treatment planning and quality assurance. Radiation treatment of locally advanced cervical cancer is evolving rapidly, driven by advances in technology, towards more individualized patient care that has the potential to substantially improve clinical outcomes.

Importance of Pharmaceutical Training and Clinical Research at Medical Facilities.

PubMed

Myotoku, Michiaki

2017-01-01

To respond to advancements in medical techniques, and to address the separation of medical and dispensary practices, clinical professors are required to educate human resource staff to become highly-skilled pharmacists. For this purpose, it is extremely important for these professors to learn about cutting-edge practical skills and knowledge, as well as to advance their expertise. In addition, they need to conduct clinical research in cooperation with relevant facilities. As our university does not have its own hospital or pharmacy, it is important to provide training for clinical professors in clinical facilities. Such training mainly involves medical teams' in-hospital rounds and participation in conferences (nutrition support team; NST), operation of the pharmacy department, and intervention targeting improvement in the department's duties. We have conducted collaborative studies, provided research instructions, implemented studies aimed at improving the department's work (pharmacists appointed on wards at all times to ensure medical safety) as well as studies regarding team medical care (nutritional evaluation during outpatient chemotherapy), and resolved issues regarding this work (drug solution mixability in a hand-held constant infusion pump, and a safe pump-filling methods). Thus, it has become possible to keep track of the current state of a pharmacists' work within team medical care, to access information about novel drugs, to view clinical and prescription-claim data, to cooperate with other professionals (e.g., doctors and nurses), to promote pharmacists' self-awareness of their roles in cooperative medical practice, and to effectively maintain the hospital's clinical settings.

Novel everting urologic access sheath: potential advantages of decreased cellular advancement.

PubMed

Camargo, Affonso H L A; Rubenstein, Jonathan N; Sozen, Sinan; Ershoff, Brent D; Stoller, Marshall L

2006-02-01

Axial forces are imposed on the urothelium during advancement of instruments across the urinary tract, potentially transferring cellular debris, bacteria, or urothelial carcinoma from one anatomic location to another. A prototype access sheath (Cystoglide; Percutaneous Systems, Mountain View, CA) was created that everts and radially dilates but does not provide axial forces during deployment that can be used in a variety of anatomic systems. We created a urinary-tract model to evaluate the in-vitro advancement of cells to compare this technology with using instruments alone. Blocks of sterile agar were created with 17F tracts of three lengths (2.7, 5.5, and 11 cm) with 5 mL of Luria-Bertani broth/ampicillin solution in a well at the end. The tips of a Cystoglide sheath and a traditional urologic instrument of the same diameter were dipped into a suspension of ampicillin-resistant Escherichia coli and advanced through the tracts. After a 10-second exposure, 4 mL of broth was collected and cultured. Bacterial growth was compared by measuring the optical density (OD) of the broth at multiple time points. The mean overall OD of the broth was significantly lower (P < 0.001) in the novel-sheath cultures than with a traditional instrument for all advancements at all tract lengths. The Cystoglide sheath significantly reduces the advancement of cells within an artificial urinary tract compared with a non-everting instrument. Clinical studies are needed to assess the utility of this technology in vivo.

Advanced upper limb prosthetic devices: implications for upper limb prosthetic rehabilitation.

PubMed

Resnik, Linda; Meucci, Marissa R; Lieberman-Klinger, Shana; Fantini, Christopher; Kelty, Debra L; Disla, Roxanne; Sasson, Nicole

2012-04-01

The number of catastrophic injuries caused by improvised explosive devices in the Afghanistan and Iraq Wars has increased public, legislative, and research attention to upper limb amputation. The Department of Veterans Affairs (VA) has partnered with the Defense Advanced Research Projects Agency and DEKA Integrated Solutions to optimize the function of an advanced prosthetic arm system that will enable greater independence and function. In this special communication, we examine current practices in prosthetic rehabilitation including trends in adoption and use of prosthetic devices, financial considerations, and the role of rehabilitation team members in light of our experiences with a prototype advanced upper limb prosthesis during a VA study to optimize the device. We discuss key challenges in the adoption of advanced prosthetic technology and make recommendations for service provision and use of advanced upper limb prosthetics. Rates of prosthetic rejection are high among upper limb amputees. However, these rates may be reduced with sufficient training by a highly specialized, multidisciplinary team of clinicians, and a focus on patient education and empowerment throughout the rehabilitation process. There are significant challenges emerging that are unique to implementing the use of advanced upper limb prosthetic technology, and a lack of evidence to establish clinical guidelines regarding prosthetic prescription and treatment. Finally, we make recommendations for future research to aid in the identification of best practices and development of policy decisions regarding insurance coverage of prosthetic rehabilitation. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials.

PubMed

Phillips, Patrick P J; Mendel, Carl M; Burger, Divan A; Crook, Angela M; Crook, Angela; Nunn, Andrew J; Dawson, Rodney; Diacon, Andreas H; Gillespie, Stephen H

2016-02-04

Despite recent increased clinical trials activity, no regimen has proved able to replace the standard 6-month regimen for drug-sensitive tuberculosis. Understanding the relationship between microbiological markers measured during treatment and long-term clinical outcomes is critical to evaluate their usefulness for decision-making for both individual patient care and for advancing novel regimens into time-consuming and expensive pivotal phase III trials. Using data from the randomized controlled phase III trial REMoxTB, we evaluated sputum-based markers of speed of clearance of bacilli: time to smear negative status; time to culture negative status on LJ or in MGIT; daily rate of change of log10(TTP) to day 56; and smear or culture results at weeks 6, 8 or 12; as individual- and trial-level surrogate endpoints for long-term clinical outcome. Time to culture negative status on LJ or in MGIT, time to smear negative status and daily rate of change in log10(TTP) were each independent predictors of clinical outcome, adjusted for treatment (p <0.001). However, discrimination between low and high risk patients, as measured by the c-statistic, was modest and not much higher than the reference model adjusted for BMI, history of smoking, HIV status, cavitation, gender and MGIT TTP. Culture conversion during treatment for tuberculosis, however measured, has only a limited role in decision-making for advancing regimens into phase III trials or in predicting the outcome of treatment for individual patients. REMoxTB ClinicalTrials.gov number: NCT00864383.

A multidisciplinary prostate cancer clinic for newly diagnosed patients: developing the role of the advanced practice nurse.

PubMed

Madsen, Lydia T; Craig, Catherine; Kuban, Deborah

2009-06-01

Newly diagnosed patients with prostate cancer have various treatment options, and a multidisciplinary prostate cancer clinic (MPCC) can present all options in a single setting. An MPCC was started in 2004 at the University of Texas M.D. Anderson Cancer Center, and 258 patients with prostate cancer were evaluated in its first year. The clinic expanded in 2006 and an oncology advanced practice nurse (APN) was recruited to address specific objectives. The APN role was used to implement a quality-of-life protocol, provide detailed patient education (including a treatment summary and care plan), and serve as a single point of contact as patients move toward a treatment decision. Formal evaluation of the MPCC showed that patients were satisfied with this approach to the complex decision-making process in prostate cancer.

New directions in hypnosis research: strategies for advancing the cognitive and clinical neuroscience of hypnosis

PubMed Central

Jensen, Mark P; Jamieson, Graham A; Lutz, Antoine; Mazzoni, Giuliana; McGeown, William J; Santarcangelo, Enrica L; Demertzi, Athena; De Pascalis, Vilfredo; Bányai, Éva I; Rominger, Christian; Vuilleumier, Patrik; Faymonville, Marie-Elisabeth; Terhune, Devin B

2017-01-01

Abstract This article summarizes key advances in hypnosis research during the past two decades, including (i) clinical research supporting the efficacy of hypnosis for managing a number of clinical symptoms and conditions, (ii) research supporting the role of various divisions in the anterior cingulate and prefrontal cortices in hypnotic responding, and (iii) an emerging finding that high hypnotic suggestibility is associated with atypical brain connectivity profiles. Key recommendations for a research agenda for the next decade include the recommendations that (i) laboratory hypnosis researchers should strongly consider how they assess hypnotic suggestibility in their studies, (ii) inclusion of study participants who score in the middle range of hypnotic suggestibility, and (iii) use of expanding research designs that more clearly delineate the roles of inductions and specific suggestions. Finally, we make two specific suggestions for helping to move the field forward including (i) the use of data sharing and (ii) redirecting resources away from contrasting state and nonstate positions toward studying (a) the efficacy of hypnotic treatments for clinical conditions influenced by central nervous system processes and (b) the neurophysiological underpinnings of hypnotic phenomena. As we learn more about the neurophysiological mechanisms underlying hypnosis and suggestion, we will strengthen our knowledge of both basic brain functions and a host of different psychological functions. PMID:29034102

The pharmacotherapy of the HeartMate II, a continuous flow left ventricular assist device, in patients with advanced heart failure: integration of disease, device, and drug.

PubMed

Jennings, Douglas L; Chambers, Rachel M; Schillig, Jessica M

2010-10-01

Advanced heart failure continues to be a significant cause of morbidity and mortality in the US. Patients with advanced heart failure have a poor prognosis without cardiac transplantation. The use of left ventricular assist devices (LVADs) as destination therapy for these patients is therefore expected to increase in the coming years as technology advances. The HeartMate II, a continuous flow implantable device, is currently the only LVAD that has been approved by the Food and Drug Administration for destination therapy in patients with advanced heart failure. The pharmacotherapy associated with this device is very complex and, therefore, the need for expertly trained clinical pharmacists to care for this expanding patient population will also likely increase. Unfortunately, most pharmacists are unfamiliar with the effect of LVADs on the physiology and pharmacotherapy of a patient's heart failure. The purpose of this article is to give clinical pharmacists an introduction to the most common pharmacotherapeutic issues for patients with LVADs and present practical solutions for managing common drug therapy problems.

Effect of Kangfuxin Solution on Chemo/Radiotherapy-Induced Mucositis in Nasopharyngeal Carcinoma Patients: A Multicenter, Prospective Randomized Phase III Clinical Study

PubMed Central

Luo, Yangkun; Feng, Mei; Fan, Zixuan; Zhu, Xiaodong; Jin, Feng; Li, Rongqing; Wu, Jingbo; Yang, Xia; Jiang, Qinghua; Bai, Hongfang; Huang, Yecai; Lang, Jinyi

2016-01-01

Objective. To evaluate the efficacy and safety of Kangfuxin Solution, a pure Chinese herbal medicine, on mucositis induced by chemoradiotherapy in nasopharyngeal carcinoma patients. Methods. A randomized, parallel-group, multicenter clinical study was performed. A total of 240 patients were randomized to receive either Kangfuxin Solution (test group) or compound borax gargle (control group) during chemoradiotherapy. Oral mucositis, upper gastrointestinal mucositis, and oral pain were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and the Verbal Rating Scale (VRS). Results. Of 240 patients enrolled, 215 were eligible for efficacy analysis. Compared with the control group, the incidence and severity of oral mucositis in the test group were significantly reduced (P = 0.01). The time to different grade of oral mucositis occurrence (grade 1, 2, or 3) was longer in test group (P < 0.01), and the accumulated radiation dose was also higher in test group comparing to the control group (P < 0.05). The test group showed lower incidence of oral pain and gastrointestinal mucositis than the control group (P < 0.01). No significant adverse events were observed. Conclusion. Kangfuxin Solution demonstrated its superiority to compound borax gargle on mucositis induced by chemoradiotherapy. Its safety is acceptable for clinical application. PMID:27375766

Tracking Patient Encounters and Clinical Skills to Determine Competency in Ambulatory Care Advanced Pharmacy Practice Experiences

PubMed Central

Pereira, Chrystian R.; Harris, Ila M.; Moon, Jean Y.; Westberg, Sarah M.; Kolar, Claire

2016-01-01

Objective. To determine if the amount of exposure to patient encounters and clinical skills correlates to student clinical competency on ambulatory care advanced pharmacy practice experiences (APPEs). Design. Students in ambulatory care APPEs tracked the number of patients encountered by medical condition and the number of patient care skills performed. At the end of the APPE, preceptors evaluated students’ competency for each medical condition and skill, referencing the Dreyfus model for skill acquisition. Assessment. Data was collected from September 2012 through August 2014. Forty-six responses from a student tracking tool were matched to preceptor ratings. Students rated as competent saw more patients and performed more skills overall. Preceptors noted minimal impact on workload. Conclusions. Increased exposure to patient encounters and skills performed had a positive association with higher Dreyfus stage, which may represent a starting point in the conversation for more thoughtful design of ambulatory care APPEs. PMID:26941440

Implementation of clinical research trials using web-based and mobile devices: challenges and solutions.

PubMed

Eagleson, Roy; Altamirano-Diaz, Luis; McInnis, Alex; Welisch, Eva; De Jesus, Stefanie; Prapavessis, Harry; Rombeek, Meghan; Seabrook, Jamie A; Park, Teresa; Norozi, Kambiz

2017-03-17

With the increasing implementation of web-based, mobile health interventions in clinical trials, it is crucial for researchers to address the security and privacy concerns of patient information according to high ethical standards. The full process of meeting these standards is often made more complicated due to the use of internet-based technology and smartphones for treatment, telecommunication, and data collection; however, this process is not well-documented in the literature. The Smart Heart Trial is a single-arm feasibility study that is currently assessing the effects of a web-based, mobile lifestyle intervention for overweight and obese children and youth with congenital heart disease in Southwestern Ontario. Participants receive telephone counseling regarding nutrition and fitness; and complete goal-setting activities on a web-based application. This paper provides a detailed overview of the challenges the study faced in meeting the high standards of our Research Ethics Board, specifically regarding patient privacy. We outline our solutions, successes, limitations, and lessons learned to inform future similar studies; and model much needed transparency in ensuring high quality security and protection of patient privacy when using web-based and mobile devices for telecommunication and data collection in clinical research.

An overview of measurement solutions for digital systems

NASA Astrophysics Data System (ADS)

Lemke, D.

An overview of digital measurement solutions is presented. A summary of the digital instrumentation that is currently available on the commercial market is given. The technology trends that are driving commercial instrumentation suppliers to provide newer and more advanced features and better measurement solutions for the future is reviewed. The implications of developments in design automation for electrical engineers is discussed.

Is it feasible to discuss an advance directive with a Chinese patient with advanced malignancy? A prospective cohort study.

PubMed

Wong, S Y; Lo, S H; Chan, C H; Chui, H S; Sze, W K; Tung, Y

2012-06-01

Advance directives have been implemented for years in western countries, but the concept is new to Asian cultures. According to traditional Chinese culture, family members usually play a decisive role in a patient's treatment plan. Thus it may be hard to implement an advance directive despite its importance to the treatment of patients. The objectives of this study were to assess the feasibility of advance directive engagement and to explore significant contributing factors to achieving such a goal. Prospective cohort study. Palliative Care Unit of Clinical Oncology, Tuen Mun Hospital, Hong Kong. The subjects of the investigation were adult patients diagnosed to have advanced malignancy and newly referred to the hospice service from 24 April 2009 to 30 July 2009. Data were collected from nursing assessment forms, locally designed advance directive forms, a checklist completed by oncologists, and details available in the electronic hospital record. Of the 191 eligible patients, 120 (63%) had the advance directive, whereas 71 (37%) did not. In the Cox regression model, the patient having insight of a poor prognosis was the most significant factor facilitating advance directive engagement (P=0.001). Any family objection in the discussion of advance directives was also an important factor, though it did not reach statistical significance (P=0.082). Other factors like age, gender, education, religion, financial status, living environment, understanding the diagnosis, bereavement experience, type of cancer, nature of illness, courses of chemotherapy or radiotherapy received, main caregiver, in-house supporter, nurse-led clinic attendance, clinical psychologist consultation, and in-patient hospice nurse coordinator interview were all statistically insignificant. Our study demonstrated that it was feasible to discuss an advance directive with Chinese patients with advanced malignancy. When patients have insight about their poor prognosis and family members have no

Advanced systemic mastocytosis: from molecular and genetic progress to clinical practice.

PubMed

Ustun, Celalettin; Arock, Michel; Kluin-Nelemans, Hanneke C; Reiter, Andreas; Sperr, Wolfgang R; George, Tracy; Horny, Hans-Peter; Hartmann, Karin; Sotlar, Karl; Damaj, Gandhi; Hermine, Olivier; Verstovsek, Srdan; Metcalfe, Dean D; Gotlib, Jason; Akin, Cem; Valent, Peter

2016-10-01

Systemic mastocytosis is a heterogeneous disease characterized by the accumulation of neoplastic mast cells in the bone marrow and other organ organs/tissues. Mutations in KIT, most frequently KIT D816V, are detected in over 80% of all systemic mastocytosis patients. While most systemic mastocytosis patients suffer from an indolent disease variant, some present with more aggressive variants, collectively called "advanced systemic mastocytosis", which include aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic, clonal non mast cell-lineage disease, and mast cell leukemia. Whereas patients with indolent systemic mastocytosis have a near normal life expectancy, patients with advanced systemic mastocytosis have a reduced life expectancy. Although cladribine and interferon-alpha are of benefit in a group of patients with advanced systemic mastocytosis, no curative therapy is available for these patients except possible allogeneic hematopoietic stem cell transplantation. Recent studies have also revealed additional somatic defects (apart from mutations in KIT) in a majority of patients with advanced systemic mastocytosis. These include TET2, SRSF2, ASXL1, RUNX1, JAK2, and/or RAS mutations, which may adversely impact prognosis and survival in particular systemic mastocytosis with an associated hematological neoplasm. In addition, several additional signaling molecules involved in the abnormal proliferation of mast cells in systemic mastocytosis have been identified. These advances have led to a better understanding of the biology of advanced systemic mastocytosis and to the development of new targeted treatment concepts. Herein, we review the biology and pathogenesis of advanced systemic mastocytosis, with a special focus on novel molecular findings as well as current and evolving therapeutic options. Copyright© Ferrata Storti Foundation.

Advanced plasma etch technologies for nanopatterning

NASA Astrophysics Data System (ADS)

Wise, Rich

2013-10-01

Advances in patterning techniques have enabled the extension of immersion lithography from 65/45 nm through 14/10 nm device technologies. A key to this increase in patterning capability has been innovation in the subsequent dry plasma etch processing steps. Multiple exposure techniques, such as litho-etch-litho-etch, sidewall image transfer, line/cut mask, and self-aligned structures, have been implemented to solution required device scaling. Advances in dry plasma etch process control across wafer uniformity and etch selectivity to both masking materials have enabled adoption of vertical devices and thin film scaling for increased device performance at a given pitch. Plasma etch processes, such as trilayer etches, aggressive critical dimension shrink techniques, and the extension of resist trim processes, have increased the attainable device dimensions at a given imaging capability. Precise control of the plasma etch parameters affecting across-design variation, defectivity, profile stability within wafer, within lot, and across tools has been successfully implemented to provide manufacturable patterning technology solutions. IBM has addressed these patterning challenges through an integrated total patterning solutions team to provide seamless and synergistic patterning processes to device and integration internal customers. We will discuss these challenges and the innovative plasma etch solutions pioneered by IBM and our alliance partners.

Advanced plasma etch technologies for nanopatterning

NASA Astrophysics Data System (ADS)

Wise, Rich

2012-03-01

Advances in patterning techniques have enabled the extension of immersion lithography from 65/45nm through 14/10nm device technologies. A key to this increase in patterning capability has been innovation in the subsequent dry plasma etch processing steps. Multiple exposure techniques such as litho-etch-litho-etch, sidewall image transfer, line/cut mask and self-aligned structures have been implemented to solution required device scaling. Advances in dry plasma etch process control, across wafer uniformity and etch selectivity to both masking materials and have enabled adoption of vertical devices and thin film scaling for increased device performance at a given pitch. Plasma etch processes such as trilayer etches, aggressive CD shrink techniques, and the extension of resist trim processes have increased the attainable device dimensions at a given imaging capability. Precise control of the plasma etch parameters affecting across design variation, defectivity, profile stability within wafer, within lot, and across tools have been successfully implemented to provide manufacturable patterning technology solutions. IBM has addressed these patterning challenges through an integrated Total Patterning Solutions team to provide seamless and synergistic patterning processes to device and integration internal customers. This paper will discuss these challenges and the innovative plasma etch solutions pioneered by IBM and our alliance partners.

Advancing clinical development pathways for new CFTR modulators in cystic fibrosis.

PubMed

Mayer-Hamblett, Nicole; Boyle, Michael; VanDevanter, Donald

2016-05-01

Cystic fibrosis (CF) is a life-shortening genetic disease affecting approximately 70,000 individuals worldwide. Until recently, drug development efforts have emphasised therapies treating downstream signs and symptoms resulting from the underlying CF biological defect: reduced function of the CF transmembrane conductance regulator (CFTR) protein. The current CF drug development landscape has expanded to include therapies that enhance CFTR function by either restoring wild-type CFTR protein expression or increasing (modulating) the function of mutant CFTR proteins in cells. To date, two systemic small-molecule CFTR modulators have been evaluated in pivotal clinical trials in individuals with CF and specific mutant CFTR genotypes that have led to regulatory review and/or approval. Advances in the discovery of CFTR modulators as a promising new class of therapies have been impressive, yet work remains to develop highly effective, disease-modifying modulators for individuals of all CF genotypes. The objectives of this review are to outline the challenges and opportunities in drug development created by systemic genotype-specific CFTR modulators, highlight the advantages of sweat chloride as an established biomarker of CFTR activity to streamline early-phase development and summarise options for later phase clinical trial designs that respond to the adoption of approved genotype-specific modulators into standard of care. An optimal development framework will be needed to move the most promising therapies efficiently through the drug development pipeline and ultimately deliver efficacious and safe therapies to all individuals with CF. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The efficacy and safety of neoadjuvant chemotherapy +/- letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial.

PubMed

Mohammadianpanah, Mohammad; Ashouri, Yaghoub; Hoseini, Sare; Amadloo, Niloofar; Talei, Abdolrasoul; Tahmasebi, Sedigheh; Nasrolahi, Hamid; Mosalaei, Ahmad; Omidvari, Shapour; Ansari, Mansour; Mosleh-Shirazi, Mohammad Amin

2012-04-01

This two-arm randomized clinical study aimed to evaluate the efficacy and safety of neoadjuvant concurrent chemotherapy and letrozole in postmenopausal women with locally advanced breast carcinoma. One hundred and one postmenopausal women aged 50-83 years with pathologically proven locally advanced (clinical stage T3, T4 and/or N2, N3) breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (control arm, n = 51) or neoadjuvant chemotherapy concurrent with letrozole 2.5 mg (study arm, n = 50). Chemotherapy consisted of a median 4 (range 3-5) cycles of intravenous 5-fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 600 mg/m(2), every three weeks. All patients subsequently underwent modified radical mastectomy approximately two weeks after the last cycle of chemotherapy. Pathologic complete response rates were 25.5% and 10.2% in the study and the control group, respectively (P = 0.049). Similarly, clinical complete response rates were 27.6% and 10.2% in the study and the control group, respectively (P = 0.037). In the subgroup analysis of hormone receptor-positive cases, the complete response rates were more prominent in study group compared with control group. Common treatment-related side effects such as nausea, vomiting, bone marrow suppression, and mucositis were similar in both groups, but hot flush was more prevalent in study group compared with control group (P = 0.023). The addition of letrozole concurrently with neoadjuvant chemotherapy provides a higher clinical and pathologic response rates with acceptable toxicity compared with chemotherapy alone in postmenopausal women with locally advanced sensitive breast cancer.

Considering context in academic medicine: differences in demographic and professional characteristics and in research productivity and advancement metrics across seven clinical departments.

PubMed

Warner, Erica T; Carapinha, René; Weber, Griffin M; Hill, Emorcia V; Reede, Joan Y

2015-08-01

To understand the disciplinary contexts in which faculty work, the authors examined demographics, professional characteristics, research productivity, and advancement across seven clinical departments at Harvard Medical School (HMS) and nationally. HMS analyses included faculty from seven clinical departments-anesthesiology, medicine, neurology, pediatrics, psychiatry, radiology, and surgery-in May 2011 (N = 7,304). National analyses included faculty at 141 U.S. medical schools in the same seven departments as of December 31, 2011 (N = 91,414). The authors used chi-square and Wilcoxon Mann-Whitney tests to compare departmental characteristics. Heterogeneity in demographics, professional characteristics, and advancement across departments was observed in HMS and national data. At HMS, psychiatry had the highest percentage of underrepresented minority faculty at 6.6% (75/1,139). In anesthesiology, 24.2% (128/530) of faculty were Asian, whereas in psychiatry only 7.9% (90/1,139) were (P < .0001). Female faculty were the majority in pediatrics and psychiatry, whereas in surgery 26.3% (172/654) of the faculty were female (P < .0001). At HMS, surgery, radiology, and neurology had the shortest median times to promotion and the highest median number of publications, H-index, and second-degree centrality. Neurology also had the highest percentage of faculty who had been principal investigators on a National Institutes of Health-funded grant. There were differences in demographics, professional characteristics, and advancement across clinical departments at HMS and nationally. The context in which faculty work, of which department is a proxy, should be accounted for in research on faculty career outcomes and diversity inclusion in academic medicine.

Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer.

PubMed

Rafii, Saeed; Gourley, Charlie; Kumar, Rajiv; Geuna, Elena; Ern Ang, Joo; Rye, Tzyvia; Chen, Lee-May; Shapira-Frommer, Ronnie; Friedlander, Michael; Matulonis, Ursula; De Greve, Jacques; Oza, Amit M; Banerjee, Susana; Molife, L Rhoda; Gore, Martin E; Kaye, Stan B; Yap, Timothy A

2017-07-18

The PARP inhibitor olaparib was recently granted Food and Drug Administration (FDA) accelerated approval in patients with advanced BRCA1/2 mutation ovarian cancer. However, antitumor responses are observed in only approximately 40% of patients and the impact of baseline clinical factors on response to treatment remains unclear. Although platinum sensitivity has been suggested as a marker of response to PARP inhibitors, patients with platinum-resistant disease still respond to olaparib. 108 patients with advanced BRCA1/2 mutation ovarian cancers were included. The interval between the end of the most recent platinum chemotherapy and PARPi (PTPI) was used to predict response to olaparib independent of conventional definition of platinum sensitivity. RECIST complete response (CR) and partial response (PR) rates were 35% in patients with platinum-sensitive versus 13% in platinum-resistant (p<0.005). Independent of platinum sensitivity status, the RECIST CR/PR rates were 42% in patients with PTPI greater than 52 weeks and 18% in patients with PTPI less than 52 weeks (p=0.016). No association was found between baseline clinical factors such as FIGO staging, debulking surgery, BRCA1 versus BRCA2 mutations, prior history of breast cancer and prior chemotherapy for breast cancer, and the response to olaparib. We conducted an international multicenter retrospective study to investigate the association between baseline clinical characteristics of patients with advanced BRCA1/2 mutation ovarian cancers from eight different cancer centers and their antitumor response to olaparib. PTPI may be used to refine the prediction of response to PARP inhibition based on the conventional categorization of platinum sensitivity.

Advanced Practice Registered Nurses and Physician Assistants in Sleep Centers and Clinics: A Survey of Current Roles and Educational Background

PubMed Central

Colvin, Loretta; Cartwright, Ann; Collop, Nancy; Freedman, Neil; McLeod, Don; Weaver, Terri E.; Rogers, Ann E.

2014-01-01

Study Objectives: To survey Advanced Practice Registered Nurse (APRN) and Physician Assistant (PA) utilization, roles and educational background within the field of sleep medicine. Methods: Electronic surveys distributed to American Academy of Sleep Medicine (AASM) member centers and APRNs and PAs working within sleep centers and clinics. Results: Approximately 40% of responding AASM sleep centers reported utilizing APRNs or PAs in predominantly clinical roles. Of the APRNs and PAs surveyed, 95% reported responsibilities in sleep disordered breathing and more than 50% in insomnia and movement disorders. Most APRNs and PAs were prepared at the graduate level (89%), with sleep-specific education primarily through “on the job” training (86%). All APRNs surveyed were Nurse Practitioners (NPs), with approximately double the number of NPs compared to PAs. Conclusions: APRNs and PAs were reported in sleep centers at proportions similar to national estimates of NPs and PAs in physicians' offices. They report predominantly clinical roles, involving common sleep disorders. Given current predictions that the outpatient healthcare structure will change and the number of APRNs and PAs will increase, understanding the role and utilization of these professionals is necessary to plan for the future care of patients with sleep disorders. Surveyed APRNs and PAs reported a significant deficiency in formal and standardized sleep-specific education. Efforts to provide formal and standardized educational opportunities for APRNs and PAs that focus on their clinical roles within sleep centers could help fill a current educational gap. Citation: Colvin L, Cartwright Ann, Collop N, Freedman N, McLeod D, Weaver TE, Rogers AE. Advanced practice registered nurses and physician assistants in sleep centers and clinics: a survey of current roles and educational background. J Clin Sleep Med 2014;10(5):581-587. PMID:24812545

Solution of plane cascade flow using improved surface singularity methods

NASA Technical Reports Server (NTRS)

Mcfarland, E. R.

1981-01-01

A solution method has been developed for calculating compressible inviscid flow through a linear cascade of arbitrary blade shapes. The method uses advanced surface singularity formulations which were adapted from those found in current external flow analyses. The resulting solution technique provides a fast flexible calculation for flows through turbomachinery blade rows. The solution method and some examples of the method's capabilities are presented.

Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers

PubMed Central

Blakely, Collin M.; Watkins, Thomas B.K.; Wu, Wei; Gini, Beatrice; Chabon, Jacob J.; McCoach, Caroline E.; McGranahan, Nicholas; Wilson, Gareth A.; Birkbak, Nicolai J.; Olivas, Victor R.; Rotow, Julia; Maynard, Ashley; Wang, Victoria; Gubens, Matthew A.; Banks, Kimberly C.; Lanman, Richard B.; Caulin, Aleah F.; John, John St.; Cordero, Anibal R.; Giannikopoulos, Petros; Simmons, Andrew D.; Mack, Philip C.; Gandara, David R.; Husain, Hatim; Doebele, Robert C.; Riess, Jonathan W.; Diehn, Maximilian; Swanton, Charles; Bivona, Trever G.

2017-01-01

A widespread approach to modern cancer therapy is to identify a single oncogenic driver gene and target its mutant protein product (e.g. EGFR inhibitor treatment in EGFR-mutant lung cancers). However, genetically-driven resistance to targeted therapy limits patient survival. Through genomic analysis of 1122 EGFR-mutant lung cancer cell-free DNA samples and whole exome analysis of seven longitudinally collected tumor samples from an EGFR-mutant lung cancer patient, we identify critical co-occurring oncogenic events present in most advanced-stage EGFR-mutant lung cancers. We define new pathways limiting EGFR inhibitor response, including WNT/β-catenin and cell cycle gene (e.g. CDK4, CDK6) alterations. Tumor genomic complexity increases with EGFR inhibitor treatment and co-occurring alterations in CTNNB1, and PIK3CA exhibit non-redundant functions that cooperatively promote tumor metastasis or limit EGFR inhibitor response. This study challenges the prevailing single-gene driver oncogene view and links clinical outcomes to co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancer patients. PMID:29106415

In utero stem cell transplantation and gene therapy: rationale, history, and recent advances toward clinical application

PubMed Central

Almeida-Porada, Graça; Atala, Anthony; Porada, Christopher D

2016-01-01

Recent advances in high-throughput molecular testing have made it possible to diagnose most genetic disorders relatively early in gestation with minimal risk to the fetus. These advances should soon allow widespread prenatal screening for the majority of human genetic diseases, opening the door to the possibility of treatment/correction prior to birth. In addition to the obvious psychological and financial benefits of curing a disease in utero, and thereby enabling the birth of a healthy infant, there are multiple biological advantages unique to fetal development, which provide compelling rationale for performing potentially curative treatments, such as stem cell transplantation or gene therapy, prior to birth. Herein, we briefly review the fields of in utero transplantation (IUTx) and in utero gene therapy and discuss the biological hurdles that have thus far restricted success of IUTx to patients with immunodeficiencies. We then highlight several recent experimental breakthroughs in immunology, hematopoietic/marrow ontogeny, and in utero cell delivery, which have collectively provided means of overcoming these barriers, thus setting the stage for clinical application of these highly promising therapies in the near future. PMID:27069953

Circulating tumor DNA evaluated by Next-Generation Sequencing is predictive of tumor response and prolonged clinical benefit with nivolumab in advanced non-small cell lung cancer.

PubMed

Giroux Leprieur, Etienne; Herbretau, Guillaume; Dumenil, Coraline; Julie, Catherine; Giraud, Violaine; Labrune, Sylvie; Dumoulin, Jennifer; Tisserand, Julie; Emile, Jean-François; Blons, Hélène; Chinet, Thierry

2018-01-01

Nivolumab is an anti-PD1 antibody, given in second-line or later treatment in advanced non-small cell lung cancer (NSCLC). The objective of this study was to describe the predictive value of circulating tumor DNA (ctDNA) on the efficacy of nivolumab in advanced NSCLC. We prospectively included all consecutive patients with advanced NSCLC treated with nivolumab in our Department between June 2015 and October 2016. Plasma samples were obtained before the first injection of nivolumab and at the first tumor evaluation with nivolumab. ctDNA was analyzed by Next-Generation Sequencing (NGS), and the predominant somatic mutation was followed for each patient and correlated with tumor response, clinical benefit (administration of nivolumab for more than 6 months), and progression-free survival (PFS). Of 23 patients, 15 had evaluable NGS results at both times of analysis. ctDNA concentration at the first tumor evaluation and ctDNA change correlated with tumor response, clinical benefit and PFS. ROC curve analyses showed good diagnostic performances for tumor response and clinical benefit, both for ctDNA concentration at the first tumor evaluation (tumor response: positive predictive value (PPV) at 100.0% and negative predictive value (NPV) at 71.0%; clinical benefit: PPV at 83.3% and NPV 77.8%) and the ctDNA change (tumor response: PPV 100.0% and NPV 62.5%; clinical benefit: PPV 100.0% and NPV 80.0%). Patients without ctDNA concentration increase >9% at 2 months had a long-term benefit of nivolumab. In conclusion, NGS analysis of ctDNA allows the early detection of tumor response and long-term clinical benefit with nivolumab in NSCLC.

Analysis of clinically important factors on the performance of advanced hydraulic, microprocessor-controlled exo-prosthetic knee joints based on 899 trial fittings

PubMed Central

Hahn, Andreas; Lang, Michael; Stuckart, Claudia

2016-01-01

Abstract The objective of this work is to evaluate whether clinically important factors may predict an individual's capability to utilize the functional benefits provided by an advanced hydraulic, microprocessor-controlled exo-prosthetic knee component. This retrospective cross-sectional cohort analysis investigated the data of above knee amputees captured during routine trial fittings. Prosthetists rated the performance indicators showing the functional benefits of the advanced maneuvering capabilities of the device. Subjects were asked to rate their perception. Simple and multiple linear and logistic regression was applied. Data from 899 subjects with demographics typical for the population were evaluated. Ability to vary gait speed, perform toileting, and ascend stairs were identified as the most sensitive performance predictors. Prior C-Leg users showed benefits during advanced maneuvering. Variables showed plausible and meaningful effects, however, could not claim predictive power. Mobility grade showed the largest effect but also failed to be predictive. Clinical parameters such as etiology, age, mobility grade, and others analyzed here do not suffice to predict individual potential. Daily walking distance may pose a threshold value and be part of a predictive instrument. Decisions based solely on single parameters such as mobility grade rating or walking distance seem to be questionable. PMID:27828871

Effects of facilitated family case conferencing for advanced dementia: A cluster randomised clinical trial

PubMed Central

2017-01-01

Background Palliative care planning for nursing home residents with advanced dementia is often suboptimal. This study compared effects of facilitated case conferencing (FCC) with usual care (UC) on end-of-life care. Methods A two arm parallel cluster randomised controlled trial was conducted. The sample included people with advanced dementia from 20 Australian nursing homes and their families and professional caregivers. In each intervention nursing home (n = 10), Palliative Care Planning Coordinators (PCPCs) facilitated family case conferences and trained staff in person-centred palliative care for 16 hours per week over 18 months. The primary outcome was family-rated quality of end-of-life care (End-of-Life Dementia [EOLD] Scales). Secondary outcomes included nurse-rated EOLD scales, resident quality of life (Quality of Life in Late-stage Dementia [QUALID]) and quality of care over the last month of life (pharmacological/non-pharmacological palliative strategies, hospitalization or inappropriate interventions). Results Two-hundred-eighty-six people with advanced dementia took part but only 131 died (64 in UC and 67 in FCC which was fewer than anticipated), rendering the primary analysis under-powered with no group effect seen in EOLD scales. Significant differences in pharmacological (P < 0.01) and non-pharmacological (P < 0.05) palliative management in last month of life were seen. Intercurrent illness was associated with lower family-rated EOLD Satisfaction with Care (coefficient 2.97, P < 0.05) and lower staff-rated EOLD Comfort Assessment with Dying (coefficient 4.37, P < 0.01). Per protocol analyses showed positive relationships between EOLD and staff hours to bed ratios, proportion of residents with dementia and staff attitudes. Conclusion FCC facilitates a palliative approach to care. Future trials of case conferencing should consider outcomes and processes regarding decision making and planning for anticipated events and acute illness. Trial registration

Managing dyspnea in patients with advanced chronic obstructive pulmonary disease: A Canadian Thoracic Society clinical practice guideline

PubMed Central

Marciniuk, Darcy D; Goodridge, Donna; Hernandez, Paul; Rocker, Graeme; Balter, Meyer; Bailey, Pat; Ford, Gordon; Bourbeau, Jean; O’Donnell, Denis E; Maltais, Francois; Mularski, Richard A; Cave, Andrew J; Mayers, Irvin; Kennedy, Vicki; Oliver, Thomas K; Brown, Candice

2011-01-01

Dyspnea is a cardinal symptom of chronic obstructive pulmonary disease (COPD), and its severity and magnitude increases as the disease progresses, leading to significant disability and a negative effect on quality of life. Refractory dyspnea is a common and difficult symptom to treat in patients with advanced COPD. There are many questions concerning optimal management and, specifically, whether various therapies are effective in this setting. The present document was compiled to address these important clinical issues using an evidence-based systematic review process led by a representative interprofessional panel of experts. The evidence supports the benefits of oral opioids, neuromuscular electrical stimulation, chest wall vibration, walking aids and pursed-lip breathing in the management of dyspnea in the individual patient with advanced COPD. Oxygen is recommended for COPD patients with resting hypoxemia, but its use for the targeted management of dyspnea in this setting should be reserved for patients who receive symptomatic benefit. There is insufficient evidence to support the routine use of anxiolytic medications, nebulized opioids, acupuncture, acupressure, distractive auditory stimuli (music), relaxation, hand-held fans, counselling programs or psychotherapy. There is also no evidence to support the use of supplemental oxygen to reduce dyspnea in nonhypoxemic patients with advanced COPD. Recognizing the current unfamiliarity with prescribing and dosing of opioid therapy in this setting, a potential approach for their use is illustrated. The role of opioid and other effective therapies in the comprehensive management of refractory dyspnea in patients with advanced COPD is discussed. PMID:21499589

Clinical bacteriology in low-resource settings: today's solutions.

PubMed

Ombelet, Sien; Ronat, Jean-Baptiste; Walsh, Timothy; Yansouni, Cedric P; Cox, Janneke; Vlieghe, Erika; Martiny, Delphine; Semret, Makeda; Vandenberg, Olivier; Jacobs, Jan

2018-03-05

Low-resource settings are disproportionately burdened by infectious diseases and antimicrobial resistance. Good quality clinical bacteriology through a well functioning reference laboratory network is necessary for effective resistance control, but low-resource settings face infrastructural, technical, and behavioural challenges in the implementation of clinical bacteriology. In this Personal View, we explore what constitutes successful implementation of clinical bacteriology in low-resource settings and describe a framework for implementation that is suitable for general referral hospitals in low-income and middle-income countries with a moderate infrastructure. Most microbiological techniques and equipment are not developed for the specific needs of such settings. Pending the arrival of a new generation diagnostics for these settings, we suggest focus on improving, adapting, and implementing conventional, culture-based techniques. Priorities in low-resource settings include harmonised, quality assured, and tropicalised equipment, consumables, and techniques, and rationalised bacterial identification and testing for antimicrobial resistance. Diagnostics should be integrated into clinical care and patient management; clinically relevant specimens must be appropriately selected and prioritised. Open-access training materials and information management tools should be developed. Also important is the need for onsite validation and field adoption of diagnostics in low-resource settings, with considerable shortening of the time between development and implementation of diagnostics. We argue that the implementation of clinical bacteriology in low-resource settings improves patient management, provides valuable surveillance for local antibiotic treatment guidelines and national policies, and supports containment of antimicrobial resistance and the prevention and control of hospital-acquired infections. Copyright © 2018 Elsevier Ltd. All rights reserved.

Advances and new directions in crystallization control.

PubMed

Nagy, Zoltan K; Braatz, Richard D

2012-01-01

The academic literature on and industrial practice of control of solution crystallization processes have seen major advances in the past 15 years that have been enabled by progress in in-situ real-time sensor technologies and driven primarily by needs in the pharmaceutical industry for improved and more consistent quality of drug crystals. These advances include the accurate measurement of solution concentrations and crystal characteristics as well as the first-principles modeling and robust model-based and model-free feedback control of crystal size and polymorphic identity. Research opportunities are described in model-free controller design, new crystallizer designs with enhanced control of crystal size distribution, strategies for the robust control of crystal shape, and interconnected crystallization systems for multicomponent crystallization.

A qualitative analysis of how advanced practice nurses use clinical decision support systems.

PubMed

Weber, Scott

2007-12-01

The purpose of this study was to generate a grounded theory that will reflect the experiences of advanced practice nurses (APNs) working as critical care nurse practitioners (NPs) and clinical nurse specialists (CNS) with computer-based decision-making systems. A study design using grounded theory qualitative research methods and convenience sampling was employed in this study. Twenty-three APNs (13 CNS and 10 NPs) were recruited from 16 critical care units located in six large urban medical centers in the U.S. Midwest. Single-structured in-depth interviews with open-ended audio-taped questions were conducted with each APN. Through this process, APNs defined what they consider to be relevant themes and patterns of clinical decision system use in their critical care practices, and they identified the interrelatedness of the conceptual categories that emerged from the results. Data were analyzed using the constant comparative analysis method of qualitative research. APN participants were predominantly female, white/non-Hispanic, had a history of access to the clinical decision system used in their critical care settings for an average of 14 months, and had attended a formal training program to learn how to use clinical decision systems. "Forecasting decision outcomes," which was defined as the voluntary process employed to forecast the outcomes of patient care decisions in critical care prior to actual decision making, was the core variable describing system use that emerged from the responses. This variable consisted of four user constructs or components: (a) users' perceptions of their initial system learning experience, (b) users' sense of how well they understand how system technology works, (c) users' understanding of how system inferences are created or derived, and (d) users' relative trust of system-derived data. Each of these categories was further described through the grounded theory research process, and the relationships between the categories were

Advanced Traveler Information Systems (ATIS) 2.0 Precursor System: Final Report

DOT National Transportation Integrated Search

2018-03-01

Advanced Traveler Information Systems (ATIS) have experienced significant growth since their initial inception in the 1990s. Technologies have continued to evolve at a rapid pace, enabling the integration of advanced solutions for traveler informatio...

Prostate intensity-modulated radiotherapy planning in seven mouse clicks: Development of a class solution for cancer.

PubMed

Wood, Maree; Fonseca, Amara; Sampson, David; Kovendy, Andrew; Westhuyzen, Justin; Shakespeare, Thomas; Turnbull, Kirsty

2016-01-01

The aim of the retrospective study was to develop a planning class solution for prostate intensity-modulated radiotherapy (IMRT) that achieved target and organs-at-risk (OAR) doses within acceptable departmental protocol criteria using the Monaco treatment planning system (Elekta-CMS Software, MO, USA). Advances in radiation therapy technology have led to a re-evaluation of work practices. Class solutions have the potential to produce highly conformal plans in a time-efficient manner. Using data from intermediate and high risk prostate cancer patients, a stepwise quality improvement model was employed. Stage 1 involved the development of a broadly based treatment template developed across 10 patients. Stage 2 involved template refinement and clinical audit ( n  = 20); Stage 3, template review ( n  = 50) and Stage 4 an assessment of a revised template against the actual treatment plan involving 72 patients. The computer algorithm that comprised the Stage 4 template met clinical treatment criteria for 82% of patients. Minor template changes were required for a further 13% of patients. Major changes were required in 4%; one patient could not be assessed. The average calculation time was 13 min and involved seven mouse clicks by the planner. Thus, the new template met treatment criteria or required only minor changes in 95% of prostate patients; this is an encouraging result suggesting improvements in planning efficiency and consistency. It is feasible to develop a class solution for prostate IMRT using a stepwise quality improvement model which delivers clinically acceptable plans in the great majority of prostate cases.

Efficacy of fulvestrant in the treatment of postmenopausal women with endocrine-resistant advanced breast cancer in routine clinical practice.

PubMed

Blancas, I; Fontanillas, M; Conde, V; Lao, J; Martínez, E; Sotelo, M J; Jaen, A; Bayo, J L; Carabantes, F; Illarramendi, J J; Gordon, M M; Cruz, J; García-Palomo, A; Mendiola, C; Pérez-Ruiz, E; Bofill, J S; Baena-Cañada, J M; Jáñez, N M; Esquerdo, G; Ruiz-Borrego, M

2018-07-01

This study aimed to describe the efficacy of fulvestrant 500 mg in postmenopausal women with estrogen receptor (ER)-positive advanced/metastatic breast cancer who had disease progression after receiving anti-estrogen therapy in clinical practice, getting real-world data. Multicenter, retrospective, observational study conducted in Spain. Postmenopausal women with locally advanced/metastatic ER-positive breast cancer who received treatment with fulvestrant 500 mg after progression with a previous anti-estrogen therapy were eligible. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), clinical benefit rate (CBR), duration of clinical benefit (DoCB), and safety profile. A total of 263 women were evaluated (median age, 65.8 years). At a median follow-up of 21.5 months, median PFS and OS were 10.6 and 43.2 months, respectively. PFS according to 1st, 2nd, 3rd, and ≥ 4th lines were 11.5, 10.6, 9.9, and 8.5 months, respectively (p = 0.0245). PFS in patients with visceral involvement was 10 months vs 10.6 months in patients without visceral involvement (p = 0.6604), 9.6 months in patients with high Ki67 vs 10 months in patients with low Ki67 (p = 0.7224), and 10.2 months in HER2+ patients vs 10.3 months in HER2- patients (p = 0.6809). The CBR was 56.5% and the DoCB was 18.4 months. The most frequently adverse events were injection site pain (10.3%) and musculoskeletal disorders (7.6%). Fulvestrant 500 mg administered in clinical practice was shown to be effective (PFS, 10.6 months; CBR, 56.5%) and well tolerated, in accordance with previous trials.

Modern Innovative Solutions in Improving Outcomes in Chronic Obstructive Pulmonary Disease (MISSION COPD): A Comparison of Clinical Outcomes Before and After the MISSION Clinic

PubMed Central

Green, Ben; Brown, Thomas; Storrar, Will; Jones, Thomas; Fogg, Carole; Dewey, Ann; Longstaff, Jayne; Bassett, Paul

2017-01-01

Background Chronic obstructive pulmonary disorder (COPD) affects over 1 million people in the United Kingdom, and 1 person dies from COPD every 20 minutes. The cost to people with COPD and the National Health Service is huge – more than 24 million working days lost a year and the annual expenditure on COPD is £810 million and £930 million a year. Objective We aim to identify patients with COPD who are at risk of exacerbations and hospital admissions as well as those who have not been formally diagnosed, yet remain at risk. Methods This mixed-methods study will use both data and interviews from patients and health care professionals. The project Modern Innovative SolutionS in Improving Outcomes iN COPD (MISSION COPD) will hold multidisciplinary carousel style clinics to rapidly assess the patients’ COPD and related comorbidities, and enhance patient knowledge and skills for self-management. Results This study is ongoing. Conclusions This research will capture quantitative and qualitative outcomes to accompany a program of quality improvement through delivery of novel care models. PMID:28583907

Current technological advances in magnetic resonance with critical impact for clinical diagnosis and therapy.

PubMed

Runge, Val M

2013-12-01

The last 5 years of technological advances with major impact on clinical magnetic resonance (MR) are discussed, with greater emphasis on those that are most recent. These developments have already had a critical positive effect on clinical diagnosis and therapy and presage continued rapid improvements for the next 5 years. This review begins with a discussion of 2 topics that encompass the breadth of MR, in terms of anatomic applications, contrast media, and MR angiography. Subsequently, innovations are discussed by anatomic category, picking the areas with the greatest development, starting with the brain, moving forward to the liver and kidney, and concluding with the musculoskeletal system, breast, and prostate. Two final topics are then considered, which will likely, with time, become independent major fields in their own right, interventional MR and MR positron emission tomography (PET).The next decade will bring a new generation of MR contrast media, with research focused on substantial improvements (>100-fold) in relaxivity (contrast effect), thus providing greater efficacy, safety, and tissue targeting. Magnetic resonance angiography will see major advances because of the use of compressed sensing, in terms of spatial and temporal resolution, with movement away from nondynamic imaging. The breadth of available techniques and tissue contrast has greatly expanded in brain imaging, benefiting both from the introduction of new basic categories of imaging techniques, such as readout-segmented echo planar imaging and 3D fast spin echo imaging with variable flip angles, and from new refinements specific to anatomic areas, such as double inversion recovery and MP2RAGE. Liver imaging has benefited from the development of techniques to easily and rapidly assess lipid, and will see, overall, a marked improvement in the next 5 years from new techniques on the verge of clinical introduction, such as controlled aliasing in parallel imaging results in higher acceleration

Review of the clinical applications and technological advances of circulating tumor DNA in cancer monitoring.

PubMed

Chang, Yi; Tolani, Bhairavi; Nie, Xiuhong; Zhi, Xiuyi; Hu, Mu; He, Biao

2017-01-01

Circulating cell-free DNA (cfDNA) released by tumor cells, termed ctDNA, closely reflects the heterogeneity of primary cancers and their metastases. As a noninvasive, real-time monitoring biomarker, ctDNA is a promising tool for detecting driver gene mutations, assessing tumor burden and acquired resistance, and early diagnosis. However, isolation and enrichment of cfDNA is a big challenge due to the high degree of DNA fragmentation and its relatively low abundance in the bloodstream. This review aims to provide insights into the recent technological advances in acquisition of optimal quality cfDNA, the use of preservatives, isolation methods, processing timelines, and detection techniques. It also describes clinical applications of ctDNA in cancer patient management.

Clinical response to chemotherapy in locally advanced breast cancer was not associated with several polymorphisms in detoxification enzymes and DNA repair genes.

PubMed

Saadat, Mostafa; Khalili, Maryam; Nasiri, Meysam; Rajaei, Mehrdad; Omidvari, Shahpour; Saadat, Iraj

2012-03-02

The main aim of the present study was to investigate the association between several genetic polymorphisms (in glutathione S-transferase members and DNA repair genes) and clinical response to chemotherapy in locally advanced breast cancer. A sequential series of 101 patients were prospectively included in this study. Clinical assessment of treatment was accomplished by comparing initial tumor size with preoperative tumor size using revised RECIST guideline (version 1.1). Clinical response was regarded as a response or no response. There was no difference between non-responders and responders for the prevalence of genotypes of the study polymorphisms. Copyright © 2012 Elsevier Inc. All rights reserved.

Solar Energy - Solution or Pipedream?

ERIC Educational Resources Information Center

Polk, Joyce

This series of lessons and class activities is designed for presentation in a sequence of nine class days. The collection is intended to provide the student in advanced science classes with awareness of the possibilities and limitations of solar energy as a potential solution to the energy crisis. Included are discussion of the following: (1)…

Clinical effectiveness of multimodality treatment on advanced pediatric hepatoblastoma.

PubMed

Zhang, Y; Zhang, W-L; Huang, D-S; Hong, L; Wang, Y-Z; Zhu, X; Hu, H-M; Zhang, P-W; Yi, Y; Han, T

2014-01-01

To investigate the effect of multimodality treatment of advanced paediatric hepatoblastoma and the factors affecting the prognosis. 35 childhood patients were treated with multimodality treatments consisting of chemotherapy, surgery, interventional therapy, and autologous peripheral blood stem cell transplantation. Patients were followed up every month. 33 patients completed the follow-up, of which 17 were in complete remission, 5 were in partial remission, 1 case got worse, and 10 died. The remission rate was 66.7% (22/33), and the overall survival rate was 69.7% (23/33). 1 patient with advanced hepatoblastoma got high-dose chemotherapy combined with autologous peripheral blood stem cell transplantation (APBSCT) treatment, and a primary lesion by 18 x 15 x 9 cm reduced to 10 x 8 x 4 cm. Remote metastases significantly alleviated, and partial remission reached six months. The overall survival was 9 months after transplantation. Patients with the mixed phenotype of hepatoblastoma had a worse prognosis than with the epithelial phenotype (p < 0.001), and patients in stage IV had a lower survival rate than in stage III (p < 0.001). Multimodality treatment can effectively improve remission rate and prolong the survival of children with the advanced hepatoblastoma. In addition, alpha-fetoprotein (AFP), hepatoblastoma pathological classification and staging are of great use in prediction of prognosis.

Promoting the Appropriate Use of Advanced Radiation Technologies in Oncology: Summary of a National Cancer Policy Forum Workshop.

PubMed

Smith, Grace L; Ganz, Patricia A; Bekelman, Justin E; Chmura, Steven J; Dignam, James J; Efstathiou, Jason A; Jagsi, Reshma; Johnstone, Peter A; Steinberg, Michael L; Williams, Stephen B; Yu, James B; Zietman, Anthony L; Weichselbaum, Ralph R; Tina Shih, Ya-Chen

2017-03-01

Leaders in the oncology community are sounding a clarion call to promote "value" in cancer care decisions. Value in cancer care considers the clinical effectiveness, along with the costs, when selecting a treatment. To discuss possible solutions to the current obstacles to achieving value in the use of advanced technologies in oncology, the National Cancer Policy Forum of the National Academies of Sciences, Engineering, and Medicine held a workshop, "Appropriate Use of Advanced Technologies for Radiation Therapy and Surgery in Oncology" in July 2015. The present report summarizes the discussions related to radiation oncology. The workshop convened stakeholders, including oncologists, researchers, payers, policymakers, and patients. Speakers presented on key themes, including the rationale for a value discussion on advanced technology use in radiation oncology, the generation of scientific evidence for value of advanced radiation technologies, the effect of both scientific evidence and "marketplace" (or economic) factors on the adoption of technologies, and newer approaches to improving value in the practice of radiation oncology. The presentations were followed by a panel discussion with dialogue among the stakeholders. Challenges to generating evidence for the value of advanced technologies include obtaining contemporary, prospective, randomized, and representative comparative effectiveness data. Proposed solutions include the use of prospective registry data; integrating radiation oncology treatment, outcomes, and quality benchmark data; and encouraging insurance coverage with evidence development. Challenges to improving value in practice include the slow adoption of higher value and the de-adoption of lower value treatments. The proposed solutions focused on engaging stakeholders in iterative, collaborative, and evidence-based efforts to define value and promote change in radiation oncology practice. Recent examples of ongoing or successful responses to the

Internet Business Solutions

NASA Technical Reports Server (NTRS)

1997-01-01

Cogent Software, Inc. was formed in January 1995 by David Atkinson and Irene Woerner, both former employees of the Jet Propulsion Laboratory (JPL). Several other Cogent employees also worked at JPL. Atkinson headed JPL's Information Systems Technology section and Woerner lead the Advanced User Interfaces Group. Cogent's mission is to help companies organize and manage their online content by developing advanced software for the next generation of online directories and information catalogs. The company offers a complete range of Internet solutions, including Internet access, Web site design, local and wide-area networks, and custom software for online commerce applications. Cogent also offers DesignSphere Online, an electronic community for the communications arts industry. Customers range from small offices to manufacturers with thousands of employees, including Chemi-Con, one of the largest manufacturers of capacitors in the world.

Membrane separation for non-aqueous solution

NASA Astrophysics Data System (ADS)

Widodo, S.; Khoiruddin; Ariono, D.; Subagjo; Wenten, I. G.

2018-01-01

Membrane technology has been widely used in a number of applications competing with conventional technologies in various ways. Despite the enormous applications, they are mainly used for the aqueous system. The use of membrane-based processes in a non-aqueous system is an emerging area. This is because developed membranes are still limited in separations involving aqueous solution which show several drawbacks when implemented in a non-aqueous system. The purpose of this paper is to provide a review of the current application of membrane processes in non-aqueous solutions, such as mineral oil treatment, vegetable oil processing, and organic solvent recovery. Developments of advanced membrane materials for the non-aqueous solutions such as super-hydrophobic and organic solvent resistant membranes are reviewed. In addition, challenges and future outlook of membrane separation for the non-aqueous solution are discussed.

Effect of the Goals of Care Intervention for Advanced Dementia: A Randomized Clinical Trial.

PubMed

Hanson, Laura C; Zimmerman, Sheryl; Song, Mi-Kyung; Lin, Feng-Chang; Rosemond, Cherie; Carey, Timothy S; Mitchell, Susan L

2017-01-01

In advanced dementia, goals of care decisions are challenging and medical care is often more intensive than desired. To test a goals of care (GOC) decision aid intervention to improve quality of communication and palliative care for nursing home residents with advanced dementia. A single-blind cluster randomized clinical trial, including 302 residents with advanced dementia and their family decision makers in 22 nursing homes. A GOC video decision aid plus a structured discussion with nursing home health care providers; attention control with an informational video and usual care planning. Primary outcomes at 3 months were quality of communication (QOC, questionnaire scored 0-10 with higher ratings indicating better quality), family report of concordance with clinicians on the primary goal of care (endorsing same goal as the "best goal to guide care and medical treatment," and clinicians' "top priority for care and medical treatment"), and treatment consistent with preferences (Advance Care Planning Problem score). Secondary outcomes at 9 months were family ratings of symptom management and care, palliative care domains in care plans, Medical Orders for Scope of Treatment (MOST) completion, and hospital transfers. Resident-family dyads were the primary unit of analysis, and all analyses used intention-to-treat assignment. Residents' mean age was 86.5 years, 39 (12.9%) were African American, and 246 (81.5%) were women. With the GOC intervention, family decision makers reported better quality of communication (QOC, 6.0 vs 5.6; P = .05) and better end-of-life communication (QOC end-of-life subscale, 3.7 vs 3.0; P = .02). Goal concordance did not differ at 3 months, but family decision makers with the intervention reported greater concordance by 9 months or death (133 [88.4%] vs 108 [71.2%], P = .001). Family ratings of treatment consistent with preferences, symptom management, and quality of care did not differ. Residents in the intervention group had more

Surfing Global Change: Negotiating Sustainable Solutions

ERIC Educational Resources Information Center

Ahamer, Gilbert

2006-01-01

SURFING GLOBAL CHANGE (SGC) serves as a procedural shell for attaining sustainable solutions for any interdisciplinary issue and is intended for use in advanced university courses. The participants' activities evolve through five levels from individual argumentation to molding one's own views for the "common good." The paradigm of…

Potential impacts of advanced aerodynamic technology on air transportation system productivity

NASA Technical Reports Server (NTRS)

Bushnell, Dennis M. (Editor)

1994-01-01

Summaries of a workshop held at NASA Langley Research Center in 1993 to explore the application of advanced aerodynamics to airport productivity improvement are discussed. Sessions included discussions of terminal area productivity problems and advanced aerodynamic technologies for enhanced high lift and reduced noise, emissions, and wake vortex hazard with emphasis upon advanced aircraft configurations and multidisciplinary solution options.

[Clinical observation of apatinib mesylate for the treatment of multi-drug resistant advanced breast cancer].

PubMed

Lü, H M; Zhang, M W; Niu, L M; Zeng, H A; Yan, M

2018-04-24

Objective: To assess the clinical efficacy and adverse outcomes of apatinib mesylate for the treatment of multi-drug resistant advanced breast cancer. Methods: A total of 24 patients with multi-drug-resistant advanced breast cancer who underwent apatinib mesylate treatment were retrospectively analyzed at the Diagnosis and Treatment Center for Breast Cancer of Henan Cancer Hospital. Patients were reviewed every 4 weeks after initial treatment and then every 8 weeks after stable disease. Objective response rate (ORR), progression free survival (PFS), overall survival (OS) , toxicity and adverse outcomes of apatinib mesylate treatment were evaluated by imaging examinations. Results: Totally, 24 patients received apatinib mesylate at a dose of 500 mg QD. Out of the 24 patients treated, complete remission (CR) occurred in none of the patients, partial remission (PR) in 10 cases, stable disease (SD) in 10 cases, progressive disease (PD) in 4 cases, and drug with drawal in 2 cases due to adverse outcomes. Treatment with apatinib mesylate resulted in an ORR of 41.7% (10/24), disease control rate (DCR) of 83.3%, PFS of 4.7 months, and OS of 8.0 months. Adverse outcomes included proteinuria, high blood pressure, fatigue, hand-foot skin reaction (HFSR), hyperbilirubinemia, leukopenia, hair/skin pigmentation decreased. Most of the adverse events were tolerable and can be controlled after symptomatic management. Conclusions: Single-agent apatinib mesylate demonstrated the good short-term efficacy for multi-drug resistant advanced breast cancer in patients who previously underwent multiple line treatment failures. Adverse effects were controllable after symptomatic management. Treatment with apatinib mesylate maybe a viable option when other treatment modalities failed.

The Accuracy of Physicians' Clinical Predictions of Survival in Patients With Advanced Cancer.

PubMed

Amano, Koji; Maeda, Isseki; Shimoyama, Satofumi; Shinjo, Takuya; Shirayama, Hiroto; Yamada, Takeshi; Ono, Shigeki; Yamamoto, Ryo; Yamamoto, Naoki; Shishido, Hideki; Shimizu, Mie; Kawahara, Masanori; Aoki, Shigeru; Demizu, Akira; Goshima, Masahiro; Goto, Keiji; Gyoda, Yasuaki; Hashimoto, Kotaro; Otomo, Sen; Sekimoto, Masako; Shibata, Takemi; Sugimoto, Yuka; Morita, Tatsuya

2015-08-01

Accurate prognoses are needed for patients with advanced cancer. To evaluate the accuracy of physicians' clinical predictions of survival (CPS) and assess the relationship between CPS and actual survival (AS) in patients with advanced cancer in palliative care units, hospital palliative care teams, and home palliative care services, as well as those receiving chemotherapy. This was a multicenter prospective cohort study conducted in 58 palliative care service centers in Japan. The palliative care physicians evaluated patients on the first day of admission and followed up all patients to their death or six months after enrollment. We evaluated the accuracy of CPS and assessed the relationship between CPS and AS in the four groups. We obtained a total of 2036 patients: 470, 764, 404, and 398 in hospital palliative care teams, palliative care units, home palliative care services, and chemotherapy, respectively. The proportion of accurate CPS (0.67-1.33 times AS) was 35% (95% CI 33-37%) in the total sample and ranged from 32% to 39% in each setting. While the proportion of patients living longer than CPS (pessimistic CPS) was 20% (95% CI 18-22%) in the total sample, ranging from 15% to 23% in each setting, the proportion of patients living shorter than CPS (optimistic CPS) was 45% (95% CI 43-47%) in the total sample, ranging from 43% to 49% in each setting. Physicians tend to overestimate when predicting survival in all palliative care patients, including those receiving chemotherapy. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Component Analysis of Multipurpose Contact Lens Solutions To Enhance Activity against Pseudomonas aeruginosa and Staphylococcus aureus

PubMed Central

Lin, Leo; Kim, Janie; Chen, Hope; Kowalski, Regis

2016-01-01

More than 125 million people wear contact lenses worldwide, and contact lens use is the single greatest risk factor for developing microbial keratitis. We tested the antibacterial activity of multipurpose contact lens solutions and their individual component preservatives against the two most common pathogens causing bacterial keratitis, Pseudomonas aeruginosa and Staphylococcus aureus. The in vitro antibacterial activity of five multipurpose contact lens solutions (Opti-Free GP, Boston Simplus, Boston Advance, Menicare GP, and Lobob) was assayed by the standard broth dilution method. Synergy between the preservative components found in the top performing solutions was assayed using checkerboard and time-kill assays. The ISO 14729 criteria and the standard broth dilution method were used to define an optimized contact lens solution formulation against a clinical panel of drug-susceptible and drug-resistant P. aeruginosa and S. aureus strains. Preservatives with the biguanide function group, chlorhexidine and polyaminopropylbiguanide (PAPB), had the best antistaphylococcal activity, while EDTA was the best antipseudomonal preservative. The combination of chlorhexidine and EDTA had excellent synergy against P. aeruginosa. A solution formulation containing chlorhexidine (30 ppm), PAPB (5 ppm), and EDTA (5,000 ppm) had three to seven times more antipseudomonal activity than anything available to consumers today. A multipurpose contact lens solution containing a combination of chlorhexidine, PAPB, and EDTA could help to reduce the incidence of microbial keratitis for contact lens users worldwide. PMID:27139484

Physician burnout: contributors, consequences and solutions.

PubMed

West, C P; Dyrbye, L N; Shanafelt, T D

2018-06-01

Physician burnout, a work-related syndrome involving emotional exhaustion, depersonalization and a sense of reduced personal accomplishment, is prevalent internationally. Rates of burnout symptoms that have been associated with adverse effects on patients, the healthcare workforce, costs and physician health exceed 50% in studies of both physicians-in-training and practicing physicians. This problem represents a public health crisis with negative impacts on individual physicians, patients and healthcare organizations and systems. Drivers of this epidemic are largely rooted within healthcare organizations and systems and include excessive workloads, inefficient work processes, clerical burdens, work-home conflicts, lack of input or control for physicians with respect to issues affecting their work lives, organizational support structures and leadership culture. Individual physician-level factors also play a role, with higher rates of burnout commonly reported in female and younger physicians. Effective solutions align with these drivers. For example, organizational efforts such as locally developed practice modifications and increased support for clinical work have demonstrated benefits in reducing burnout. Individually focused solutions such as mindfulness-based stress reduction and small-group programmes to promote community, connectedness and meaning have also been shown to be effective. Regardless of the specific approach taken, the problem of physician burnout is best addressed when viewed as a shared responsibility of both healthcare systems and individual physicians. Although our understanding of physician burnout has advanced considerably in recent years, many gaps in our knowledge remain. Longitudinal studies of burnout's effects and the impact of interventions on both burnout and its effects are needed, as are studies of effective solutions implemented in combination. For medicine to fulfil its mission for patients and for public health, all stakeholders

Advances in Clinical Cardiology 2016: A Summary of the Key Clinical Trials.

PubMed

Gray, Alastair; McQuillan, Conor; Menown, Ian B A

2017-07-01

The findings of many new cardiology clinical trials over the last year have been published or presented at major international meetings. This paper aims to describe and place in context a summary of the key clinical trials in cardiology presented between January and December 2016. The authors reviewed clinical trials presented at major cardiology conferences during 2016 including the American College of Cardiology (ACC), European Association for Percutaneous Cardiovascular Interventions (EuroPCR), European Society of Cardiology (ESC), European Association for the Study of Diabetes (EASD), Transcatheter Cardiovascular Therapeutics (TCT), and the American Heart Association (AHA). Selection criteria were trials with a broad relevance to the cardiology community and those with potential to change current practice. A total of 57 key cardiology clinical trials were identified for inclusion. Here we describe and place in clinical context the key findings of new data relating to interventional and structural cardiology including delayed stenting following primary angioplasty, contrast-induced nephropathy, management of jailed wires, optimal duration of dual antiplatelet therapy (DAPT), stenting vs bypass for left main disease, new generation stents (BioFreedom, Orsiro, Absorb), transcatheter aortic valve implantation (Edwards Sapien XT, transcatheter embolic protection), and closure devices (Watchman, Amplatzer). New preventative cardiology data include trials of bariatric surgery, empagliflozin, liraglutide, semaglutide, PCSK9 inhibitors (evolocumab and alirocumab), and inclisiran. Antiplatelet therapy trials include platelet function monitoring and ticagrelor vs clopidogrel for peripheral vascular disease. New data are also presented in fields of heart failure (sacubitril/valsartan, aliskiren, spironolactone), atrial fibrillation (rivaroxaban in patients undergoing coronary intervention, edoxaban in DC cardioversion), cardiac devices (implantable cardioverter

Plasma genetic and genomic abnormalities predict treatment response and clinical outcome in advanced prostate cancer.

PubMed

Xia, Shu; Kohli, Manish; Du, Meijun; Dittmar, Rachel L; Lee, Adam; Nandy, Debashis; Yuan, Tiezheng; Guo, Yongchen; Wang, Yuan; Tschannen, Michael R; Worthey, Elizabeth; Jacob, Howard; See, William; Kilari, Deepak; Wang, Xuexia; Hovey, Raymond L; Huang, Chiang-Ching; Wang, Liang

2015-06-30

Liquid biopsies, examinations of tumor components in body fluids, have shown promise for predicting clinical outcomes. To evaluate tumor-associated genomic and genetic variations in plasma cell-free DNA (cfDNA) and their associations with treatment response and overall survival, we applied whole genome and targeted sequencing to examine the plasma cfDNAs derived from 20 patients with advanced prostate cancer. Sequencing-based genomic abnormality analysis revealed locus-specific gains or losses that were common in prostate cancer, such as 8q gains, AR amplifications, PTEN losses and TMPRSS2-ERG fusions. To estimate tumor burden in cfDNA, we developed a Plasma Genomic Abnormality (PGA) score by summing the most significant copy number variations. Cox regression analysis showed that PGA scores were significantly associated with overall survival (p < 0.04). After androgen deprivation therapy or chemotherapy, targeted sequencing showed significant mutational profile changes in genes involved in androgen biosynthesis, AR activation, DNA repair, and chemotherapy resistance. These changes may reflect the dynamic evolution of heterozygous tumor populations in response to these treatments. These results strongly support the feasibility of using non-invasive liquid biopsies as potential tools to study biological mechanisms underlying therapy-specific resistance and to predict disease progression in advanced prostate cancer.

Conceptualisation of the characteristics of advanced practitioners in the medical radiation professions

PubMed Central

Smith, Tony; Harris, Jillian; Woznitza, Nick; Maresse, Sharon; Sale, Charlotte

2015-01-01

Professions grapple with defining advanced practice and the characteristics of advanced practitioners. In nursing and allied health, advanced practice has been defined as ‘a state of professional maturity in which the individual demonstrates a level of integrated knowledge, skill and competence that challenges the accepted boundaries of practice and pioneers new developments in health care’. Evolution of advanced practice in Australia has been slower than in the United Kingdom, mainly due to differences in demography, the health system and industrial relations. This article describes a conceptual model of advanced practitioner characteristics in the medical radiation professions, taking into account experiences in other countries and professions. Using the CanMEDS framework, the model includes foundation characteristics of communication, collaboration and professionalism, which are fundamental to advanced clinical practice. Gateway characteristics are: clinical expertise, with high level competency in a particular area of clinical practice; scholarship and teaching, including a masters qualification and knowledge dissemination through educating others; and evidence-based practice, with judgements made on the basis of research findings, including research by the advanced practitioner. The pinnacle of advanced practice is clinical leadership, where the practitioner has a central role in the health care team, with the capacity to influence decision making and advocate for others, including patients. The proposed conceptual model is robust yet adaptable in defining generic characteristics of advanced practitioners, no matter their clinical specialty. The advanced practice roles that evolve to meet future health service demand must focus on the needs of patients, local populations and communities. PMID:26451243

Conceptualisation of the characteristics of advanced practitioners in the medical radiation professions.

PubMed

Smith, Tony; Harris, Jillian; Woznitza, Nick; Maresse, Sharon; Sale, Charlotte

2015-09-01

Professions grapple with defining advanced practice and the characteristics of advanced practitioners. In nursing and allied health, advanced practice has been defined as 'a state of professional maturity in which the individual demonstrates a level of integrated knowledge, skill and competence that challenges the accepted boundaries of practice and pioneers new developments in health care'. Evolution of advanced practice in Australia has been slower than in the United Kingdom, mainly due to differences in demography, the health system and industrial relations. This article describes a conceptual model of advanced practitioner characteristics in the medical radiation professions, taking into account experiences in other countries and professions. Using the CanMEDS framework, the model includes foundation characteristics of communication, collaboration and professionalism, which are fundamental to advanced clinical practice. Gateway characteristics are: clinical expertise, with high level competency in a particular area of clinical practice; scholarship and teaching, including a masters qualification and knowledge dissemination through educating others; and evidence-based practice, with judgements made on the basis of research findings, including research by the advanced practitioner. The pinnacle of advanced practice is clinical leadership, where the practitioner has a central role in the health care team, with the capacity to influence decision making and advocate for others, including patients. The proposed conceptual model is robust yet adaptable in defining generic characteristics of advanced practitioners, no matter their clinical specialty. The advanced practice roles that evolve to meet future health service demand must focus on the needs of patients, local populations and communities.

Conceptualisation of the characteristics of advanced practitioners in the medical radiation professions

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

Smith, Tony; Harris, Jillian; Woznitza, Nick

Professions grapple with defining advanced practice and the characteristics of advanced practitioners. In nursing and allied health, advanced practice has been defined as ‘a state of professional maturity in which the individual demonstrates a level of integrated knowledge, skill and competence that challenges the accepted boundaries of practice and pioneers new developments in health care’. Evolution of advanced practice in Australia has been slower than in the United Kingdom, mainly due to differences in demography, the health system and industrial relations. This article describes a conceptual model of advanced practitioner characteristics in the medical radiation professions, taking into account experiencesmore » in other countries and professions. Using the CanMEDS framework, the model includes foundation characteristics of communication, collaboration and professionalism, which are fundamental to advanced clinical practice. Gateway characteristics are: clinical expertise, with high level competency in a particular area of clinical practice; scholarship and teaching, including a masters qualification and knowledge dissemination through educating others; and evidence-based practice, with judgements made on the basis of research findings, including research by the advanced practitioner. The pinnacle of advanced practice is clinical leadership, where the practitioner has a central role in the health care team, with the capacity to influence decision making and advocate for others, including patients. The proposed conceptual model is robust yet adaptable in defining generic characteristics of advanced practitioners, no matter their clinical specialty. The advanced practice roles that evolve to meet future health service demand must focus on the needs of patients, local populations and communities.« less

[A prospective multicenter randomized controlled clinical study on the efficacy and safety of Guaifenesin compound pseudoephedrine hydrochloride oral solution].

PubMed

Lu, Quan

2010-03-01

To evaluate efficacy and safety of Guaifenesin compound pseudoephedrine hydrochloride oral solution for the treatment of cough, expectoration, nasal congestion and runny nose in children. This was a prospective multicenter randomized single-blind, parallel-controlled clinical study. A total of 10 centers participated in this study, the actual number of cases in line with the program was 412, of whom 205 cases in trial group were treated with Guaifenesin compound pseudoephedrine hydrochloride oral solution, and 207 cases in control group with ambroxol hydrochloride oral solution, treatment of both groups persisted for 7 days. The improvement rate of each single symptom and the combined symptoms and the overall effective rate were compared between the two groups. The adverse drug reactions and compliance were assessed as well. The treatment of both groups showed efficacy. Except sputum stickiness, the improvement of all symptoms in trial group was superior to that in the control group on the 3rd day after treatment (P < 0.05) and except nasal congestion, the efficacy in all the other symptoms of trial group was better than that in the control group as well on the 7th day (P < 0.01). The improvement rate for combined symptoms of Guaifenesin compound pseudoephedrine hydrochloride oral solution was 82.9% and the overall efficacy rate was 89.3%. Guaifenesin compound Pseudoephedrine hydrochloride oral solution had higher compliance and its adverse event rate was merely 0.92%. Guaifenesin compound pseudoephedrine hydrochloride oral solution showed significant efficacy and safety in children for treatment of cough, expectoration, nasal congestion and runny nose caused by common cold or acute tracheobronchitis.

The role of technical advances in the adoption and integration of patient-reported outcomes in clinical care.

PubMed

Jensen, Roxanne E; Rothrock, Nan E; DeWitt, Esi M; Spiegel, Brennan; Tucker, Carole A; Crane, Heidi M; Forrest, Christopher B; Patrick, Donald L; Fredericksen, Rob; Shulman, Lisa M; Cella, David; Crane, Paul K

2015-02-01

Patient-reported outcomes (PROs) are gaining recognition as key measures for improving the quality of patient care in clinical care settings. Three factors have made the implementation of PROs in clinical care more feasible: increased use of modern measurement methods in PRO design and validation, rapid progression of technology (eg, touchscreen tablets, Internet accessibility, and electronic health records), and greater demand for measurement and monitoring of PROs by regulators, payers, accreditors, and professional organizations. As electronic PRO collection and reporting capabilities have improved, the challenges of collecting PRO data have changed. To update information on PRO adoption considerations in clinical care, highlighting electronic and technical advances with respect to measure selection, clinical workflow, data infrastructure, and outcomes reporting. Five practical case studies across diverse health care settings and patient populations are used to explore how implementation barriers were addressed to promote the successful integration of PRO collection into the clinical workflow. The case studies address selecting and reporting of relevant content, workflow integration, previsit screening, effective evaluation, and electronic health record integration. These case studies exemplify elements of well-designed electronic systems, including response automation, tailoring of item selection and reporting algorithms, flexibility of collection location, and integration with patient health care data elements. They also highlight emerging logistical barriers in this area, such as the need for specialized technological and methodological expertise, and design limitations of current electronic data capture systems.

The Role of Technical Advances in the Adoption and Integration of Patient-Reported Outcomes in Clinical Care

PubMed Central

Jensen, Roxanne E.; Rothrock, Nan E.; DeWitt, Esi Morgan; Spiegel, Brennan; Tucker, Carole A.; Crane, Heidi M.; Forrest, Christopher B.; Patrick, Donald L.; Fredericksen, Rob; Shulman, Lisa M.; Cella, David; Crane, Paul K.

2016-01-01

Background Patient-reported outcomes (PROs) are gaining recognition as key measures for improving the quality of patient care in clinical care settings. Three factors have made the implementation of PROs in clinical care more feasible: increased use of modern measurement methods in PRO design and validation, rapid progression of technology (e.g., touch screen tablets, Internet accessibility, and electronic health records (EHRs)), and greater demand for measurement and monitoring of PROs by regulators, payers, accreditors, and professional organizations. As electronic PRO collection and reporting capabilities have improved, the challenges of collecting PRO data have changed. Objectives To update information on PRO adoption considerations in clinical care, highlighting electronic and technical advances with respect to measure selection, clinical workflow, data infrastructure, and outcomes reporting. Methods Five practical case studies across diverse healthcare settings and patient populations are used to explore how implementation barriers were addressed to promote the successful integration of PRO collection into the clinical workflow. The case studies address selecting and reporting of relevant content, workflow integration, pre-visit screening, effective evaluation, and EHR integration. Conclusions These case studies exemplify elements of well-designed electronic systems, including response automation, tailoring of item selection and reporting algorithms, flexibility of collection location, and integration with patient health care data elements. They also highlight emerging logistical barriers in this area, such as the need for specialized technological and methodological expertise, and design limitations of current electronic data capture systems. PMID:25588135

Advances in the understanding of the clinically relevant genetic pathways and molecular aspects of canine mammary tumours. Part 2: invasion, angiogenesis, metastasis and therapy.

PubMed

Santos, A A; Matos, A J F

2015-08-01

Significant advances have been made recently in the understanding of the molecular events and critical pathways associated with and driving cancer of the mammary gland in humans and dogs. The study of canine mammary tumour biology, particularly the interactions of neoplastic cells with stromal and immune cells, is crucial for the development of novel effective therapeutic agents and strategies. This second part of a two-part review discusses some of the latest advances in the understanding of the clinically relevant genetic and molecular pathways involved in metastasis and in the interactions between tumour and stromal cells, including inflammatory and immune cells, cancer-associated fibroblasts, and endothelial cells. Recent experimental data on the role of matrix-degrading proteases and angiogenic factors are also discussed. Finally, the clinical utility of different non-surgical therapeutic modalities is reviewed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Facing the challenges and building solutions in clinical psychiatric nursing in Iran: a qualitative study.

PubMed

Zarea, Kourosh; Nikbakht-Nasrabadi, Alireza; Abbaszadeh, Abbas; Mohammadpour, Ali

2012-10-01

Psychiatric nurses play an important role in the process of caring for mentally ill patients and are continually faced with the numerous challenges and complex issues related to this field. This study aimed to understand the perspectives of psychiatric nurses regarding the issues they face while providing care and examine the possible solutions for improvement of inpatient care in clinical settings. The study adopted a qualitative approach that utilized a content analysis of audio taped, semi-structured interviews that had been conducted with 24 nurses. Two main themes emerged from the data. The first, Challenges in Providing Care within Psychiatric Wards, had the following subthemes: Politics and Rules of Organization, Safety and Security Issues, Uncertainty about the Role, Lack of Trained Staff, and Sociocultural Issues. The second theme, Solutions for Improving Psychiatric Care, had the subthemes of Empowerment across four domains: Psychiatric Nurses, Mentally Ill Patients and their Families, The Psychiatric Mental Health System, and the Cultural Context. The results indicated that if nurses are expected to provide optimal nursing care within a psychiatric ward, then there is a need for a stable and responsible organizational structure, skilled psychiatric nurses, and community-based care along with an anti-stigma program.

Recent advances in proteomic applications for schistosomiasis research: potential clinical impact.

PubMed

Sotillo, Javier; Doolan, Denise; Loukas, Alex

2017-02-01

Schistosomiasis is a neglected tropical disease affecting hundreds of millions of people worldwide. Recent advances in the field of proteomics and the development of new and highly sensitive mass spectrometers and quantitative techniques have provided new tools for advancing the molecular biology, cell biology, diagnosis and vaccine development for public health threats such as schistosomiasis. Areas covered: In this review we describe the latest advances in research that utilizes proteomics-based tools to address some of the key challenges to developing effective interventions against schistosomiasis. We also provide information about the potential of extracellular vesicles to advance the fight against this devastating disease. Expert commentary: Different proteins are already being tested as vaccines against schistosomiasis with promising results. The re-analysis of the Schistosoma spp. proteomes using new and more sensitive mass spectrometers as well as better separation approaches will help identify more vaccine targets in a rational and informed manner. In addition, the recent development of new proteome microarrays will facilitate characterisation of novel markers of infection as well as new vaccine and diagnostic candidate antigens.

Adenoid cystic carcinoma: A review of recent advances, molecular targets, and clinical trials.

PubMed

Dillon, Patrick M; Chakraborty, Samhita; Moskaluk, Christopher A; Joshi, Prashant J; Thomas, Christopher Y

2016-04-01

Adenoid cystic carcinoma (ACC) is a rare tumor of secretory glands. In this study, recent advances in molecular characterization and in therapeutics are reviewed. A search of articles in PubMed and of abstracts from national meetings was performed regarding ACC. Recent genetic analyses found that recurrent chromosome 6:9 translocations in ACC generate an MYB:NFIB gene fusion resulting in overexpression of the MYB oncoprotein. Several other frequent mutations are recently published that may be relevant for drug development. Several trials of targeted drugs are reviewed. Some agents delay tumor progression, but tumor responses remain rare. ACCs have a characteristic chromosomal translocation, but also frequently pick up additional mutations. Clinical research is limited by the rarity and slow growth of ACC. Several ongoing trials are testing agents that inhibit fibroblast growth factor receptor signaling or other signaling pathways. Novel treatments based on the recently sequenced tumor genome are under development. © 2015 Wiley Periodicals, Inc.

Advances in Basic and Clinical Immunology 2009

PubMed Central

Chinen, Javier; Shearer, William T.

2010-01-01

In 2009, reports on basic and clinical immunology had an increased focus on human disease mechanisms and management. The molecular pathogenesis of familial angioedema associated with estrogen was further explored to find possible factors affecting severity, including polymorphisms in enzymes and receptors related to bradykinin pathways. A placebo-controlled clinical trial of C1INH concentrate in hereditary angioedema patients demonstrated the safety of its use and the efficacy to reduce duration of angioedema attacks. The interaction of innate immunity and adaptive responses was further examined in several reports establishing the significant role of toll-like receptor stimulation for the development of optimal specific antibody responses. The 2009 update of the classification of primary immunodeficiencies introduced over 15 new genetic defects related to the immune response, including DOCK8 mutations responsible for the autosomal recessive form of the hyper IgE syndrome. Other reports expanded the clinical spectrum of disease and improved the characterization of conditions such as warts, hypogammaglobulinemia and myelokathexis (WHIM) syndrome, or the occurrence of mucormycosis and Serratia infections in chronic granulomatous disease. The frequent presentation of gastrointestinal disorders in humoral immunodeficiencies was recognized and recommendations for management were reviewed. Clinical research focused in severe combined immunodeficiency included the development and implementation of a state-wide newborn screening program for this condition, a desired goal considering the significant reduction of mortality rate when diagnosis is made early before opportunistic infections occur. PMID:20226292

MO-FG-207-00: Technological Advances in PET/MR Imaging

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

NONE

2015-06-15

The use of integrated PET/MRI systems in clinical applications can best benefit from understanding their technological advances and limitations. The currently available clinical PET/MRI systems have their own characteristics. Thorough analyses of existing technical data and evaluation of necessary performance metrics for quality assurances could be conducted to optimize application-specific PET/MRI protocols. This Symposium will focus on technical advances and limitations of clinical PET/MRI systems, and how this exciting imaging modality can be utilized in applications that can benefit from both PET and MRI. Learning Objectives: To understand the technological advances of clinical PET/MRI systems To correctly identify clinical applicationsmore » that can benefit from PET/MRI To understand ongoing work to further improve the current PET/MRI technology Floris Jansen is a GE Healthcare employee.« less

Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development.

PubMed

Tomar, Dheeraj S; Kumar, Sandeep; Singh, Satish K; Goswami, Sumit; Li, Li

2016-01-01

Effective translation of breakthrough discoveries into innovative products in the clinic requires proactive mitigation or elimination of several drug development challenges. These challenges can vary depending upon the type of drug molecule. In the case of therapeutic antibody candidates, a commonly encountered challenge is high viscosity of the concentrated antibody solutions. Concentration-dependent viscosity behaviors of mAbs and other biologic entities may depend on pairwise and higher-order intermolecular interactions, non-native aggregation, and concentration-dependent fluctuations of various antibody regions. This article reviews our current understanding of molecular origins of viscosity behaviors of antibody solutions. We discuss general strategies and guidelines to select low viscosity candidates or optimize lead candidates for lower viscosity at early drug discovery stages. Moreover, strategies for formulation optimization and excipient design are also presented for candidates already in advanced product development stages. Potential future directions for research in this field are also explored.

Perimetric progression using the Visual Field Index and the Advanced Glaucoma Intervention Study score and its clinical correlations.

PubMed

Gros-Otero, Juan; Castejón, Miguel; Paz-Moreno, Javier; Mikropoulos, Dimitrios; Teus, Miguel

2015-01-01

To evaluate the association between clinical parameters and the diagnosis of progression using VFI (Visual Field Index) and AGIS (Advanced Glaucoma Intervention Study) score in primary open angle glaucoma. Retrospective study of 517 visual fields of 78 eyes with primary open angle glaucoma analyzed with VFI and AGIS score. Clinical data registered included: age, sphere, pachimetry, basal intraocular pressure (IOP), and IOP during the follow up. Only the AGIS score diagnosis of progression was associated with the clinical parameters registered. Among the analyzed data, the mean IOP during follow up (p = 0.0005) and IOP at the third month of follow up (p = 0.004) were statistically associated with progression using the AGIS criteria. The diagnosis of perimetric progression using the AGIS score in the current study was closer to the real functional progression than the diagnosis using the VFI, as the former was associated with known risk factors for progression in glaucoma. Copyright © 2014 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

Clinical evaluation of GEM 21S® and a collagen membrane with a coronally advanced flap as a root coverage procedure in the treatment of gingival recession defects: A comparative study

PubMed Central

Singh, Preetinder; Suresh, D. K.

2012-01-01

Aim: Clinical evaluation of efficacy of rhPDGF-BB plus beta tricalcium phosphate (GEM 21S®) along with a collagen membrane in root coverage using a coronally advanced flap. Materials and Methods: This human case series evaluated the clinical outcome of rhPDGF-BB with beta-tricalcium phosphate (GEM 21S®) and a collagen membrane in the treatment of recession defects using a coronally advanced flap. Patients were followed postoperatively, and healing was evaluated at 1, 3, and 6 months, with recession depth as the primary outcome measure. Results: This pioneer case series revealed a favorable tissue response to GEM 21S® and collagen membrane from both clinical and esthetic point of view in regenerative periodontal surgery. PMID:23493720

Management of advanced colon cancer in a community hospital--impact of age on clinical management and survival.

PubMed

Mogili, Sujatha; Yousaf, Mobeen; Nadaraja, Nagendra; Woodlock, Timothy

2012-09-01

Colon cancer is more common in the elderly than in younger and middle-aged people. Cancer clinical trials focus more on younger patients and the management of elderly patients with advanced disease is still unclear. We studied all patients presenting with colon adenocarcinoma metastasis to liver at a community teaching hospital from Dec 2000 through Dec 2007 by a retrospective review of Tumor Registry data and patient chart review with focus on age, clinical management, decision making, and survival. Sixty-seven patients with a median age of 69 and a male to female ratio of 31:36 were identified. The patients with obstructive symptoms and Eastern Cooperative Oncology Group performance status on presentation though varied little by age, smaller proportion of elderly patients underwent resection of the primary bowel tumor in the presence of liver metastases with ten of 16 (63%) aged 80 or greater being managed without surgery. The percentage of patient's preference to physician's preference for patients not undergoing the primary bowel resection increased for older age group. Median survival decreased significantly with age (p < 0.05). Age-related clinical management, decision-making autonomy, and survival are apparent in this study, and there was an increasing trend of patient's involvement in decision making as the age increases and, thus, affecting the age-related clinical management.

Integrative clinical genomics of advanced prostate cancer.

PubMed

Robinson, Dan; Van Allen, Eliezer M; Wu, Yi-Mi; Schultz, Nikolaus; Lonigro, Robert J; Mosquera, Juan-Miguel; Montgomery, Bruce; Taplin, Mary-Ellen; Pritchard, Colin C; Attard, Gerhardt; Beltran, Himisha; Abida, Wassim; Bradley, Robert K; Vinson, Jake; Cao, Xuhong; Vats, Pankaj; Kunju, Lakshmi P; Hussain, Maha; Feng, Felix Y; Tomlins, Scott A; Cooney, Kathleen A; Smith, David C; Brennan, Christine; Siddiqui, Javed; Mehra, Rohit; Chen, Yu; Rathkopf, Dana E; Morris, Michael J; Solomon, Stephen B; Durack, Jeremy C; Reuter, Victor E; Gopalan, Anuradha; Gao, Jianjiong; Loda, Massimo; Lis, Rosina T; Bowden, Michaela; Balk, Stephen P; Gaviola, Glenn; Sougnez, Carrie; Gupta, Manaswi; Yu, Evan Y; Mostaghel, Elahe A; Cheng, Heather H; Mulcahy, Hyojeong; True, Lawrence D; Plymate, Stephen R; Dvinge, Heidi; Ferraldeschi, Roberta; Flohr, Penny; Miranda, Susana; Zafeiriou, Zafeiris; Tunariu, Nina; Mateo, Joaquin; Perez-Lopez, Raquel; Demichelis, Francesca; Robinson, Brian D; Schiffman, Marc; Nanus, David M; Tagawa, Scott T; Sigaras, Alexandros; Eng, Kenneth W; Elemento, Olivier; Sboner, Andrea; Heath, Elisabeth I; Scher, Howard I; Pienta, Kenneth J; Kantoff, Philip; de Bono, Johann S; Rubin, Mark A; Nelson, Peter S; Garraway, Levi A; Sawyers, Charles L; Chinnaiyan, Arul M

2015-05-21

Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals. Copyright © 2015 Elsevier Inc. All rights reserved.

Integrative clinical genomics of advanced prostate cancer

PubMed Central

Dan, Robinson; Van Allen, Eliezer M.; Wu, Yi-Mi; Schultz, Nikolaus; Lonigro, Robert J.; Mosquera, Juan-Miguel; Montgomery, Bruce; Taplin, Mary-Ellen; Pritchard, Colin C; Attard, Gerhardt; Beltran, Himisha; Abida, Wassim M.; Bradley, Robert K.; Vinson, Jake; Cao, Xuhong; Vats, Pankaj; Kunju, Lakshmi P.; Hussain, Maha; Feng, Felix Y.; Tomlins, Scott A.; Cooney, Kathleen A.; Smith, David C.; Brennan, Christine; Siddiqui, Javed; Mehra, Rohit; Chen, Yu; Rathkopf, Dana E.; Morris, Michael J.; Solomon, Stephen B.; Durack, Jeremy C.; Reuter, Victor E.; Gopalan, Anuradha; Gao, Jianjiong; Loda, Massimo; Lis, Rosina T.; Bowden, Michaela; Balk, Stephen P.; Gaviola, Glenn; Sougnez, Carrie; Gupta, Manaswi; Yu, Evan Y.; Mostaghel, Elahe A.; Cheng, Heather H.; Mulcahy, Hyojeong; True, Lawrence D.; Plymate, Stephen R.; Dvinge, Heidi; Ferraldeschi, Roberta; Flohr, Penny; Miranda, Susana; Zafeiriou, Zafeiris; Tunariu, Nina; Mateo, Joaquin; Lopez, Raquel Perez; Demichelis, Francesca; Robinson, Brian D.; Schiffman, Marc A.; Nanus, David M.; Tagawa, Scott T.; Sigaras, Alexandros; Eng, Kenneth W.; Elemento, Olivier; Sboner, Andrea; Heath, Elisabeth I.; Scher, Howard I.; Pienta, Kenneth J.; Kantoff, Philip; de Bono, Johann S.; Rubin, Mark A.; Nelson, Peter S.; Garraway, Levi A.; Sawyers, Charles L.; Chinnaiyan, Arul M.

2015-01-01

SUMMARY Toward development of a precision medicine framework for metastatic, castration resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53 and PTEN were frequent (40–60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified novel genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin and ZBTB16/PLZF. Aberrations of BRCA2, BRCA1 and ATM were observed at substantially higher frequencies (19.3% overall) than seen in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides evidence that clinical sequencing in mCRPC is feasible and could impact treatment decisions in significant numbers of affected individuals. PMID:26000489

Hurdles in clinical implementation of academic advanced therapy medicinal products: A national evaluation.

PubMed

de Wilde, Sofieke; Veltrop-Duits, Louise; Hoozemans-Strik, Merel; Ras, Thirza; Blom-Veenman, Janine; Guchelaar, Henk-Jan; Zandvliet, Maarten; Meij, Pauline

2016-06-01

Since the implementation of the European Union (EU) regulation for advanced therapy medicinal products (ATMPs) in 2009, only six ATMPs achieved marketing authorization approval in the EU. Recognizing the major developments in the ATMP field, starting mostly in academic institutions, we investigated which hurdles were experienced in the whole pathway of ATMP development towards clinical care. Quality interviews were executed with different stakeholders in The Netherlands involved in the ATMP development field, e.g. academic research groups, national authorities and patient organizations. Based on the hurdles mentioned in the interviews, questionnaires were subsequently sent to the academic principal investigators (PIs) and ATMP good manufacturing practice (GMP) facility managers to quantify these hurdles. Besides the familiar regulatory routes of marketing authorization (MA) and hospital exemption (HE), a part of the academic PIs perceived that ATMPs should become available by the Tissues and Cells Directive or did not anticipate on the next development steps towards implementation of their ATMP towards regular clinical care. The main hurdles identified were: inadequate financial support, rapidly evolving field, study-related problems, lacking regulatory knowledge, lack of collaborations and responsibility issues. Creating an academic environment stimulating and planning ATMP development and licensing as well as investing in expanding the relevant regulatory knowledge in academic institutions seems a prerequisite to develop ATMPs from bench to patient. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Myositis registries and biorepositories: powerful tools to advance clinical, epidemiologic and pathogenic research

PubMed Central

Rider, Lisa G.; Dankó, Katalin; Miller, Frederick W.

2016-01-01

Purpose of review Clinical registries and biorepositories have proven extremely useful in many studies of diseases, especially rare diseases. Given their rarity and diversity, the idiopathic inflammatory myopathies, or myositis syndromes, have benefited from individual researchers’ collections of cohorts of patients. Major efforts are being made to establish large registries and biorepositories that will allow many additional studies to be performed that were not possible before. Here we describe the registries developed by investigators and patient support groups that are currently available for collaborative research purposes. Recent findings We have identified 46 myositis research registries, including many with biorepositories, which have been developed for a wide variety of purposes and have resulted in great advances in understanding the range of phenotypes, clinical presentations, risk factors, pathogenic mechanisms, outcome assessment, therapeutic responses, and prognoses. These are now available for collaborative use to undertake additional studies. Two myositis patient registries have been developed for research, and myositis patient support groups maintain demographic registries with large numbers of patients available to be contacted for potential research participation. Summary Investigator-initiated myositis research registries and biorepositories have proven extremely useful in understanding many aspects of these rare and diverse autoimmune diseases. These registries and biorepositories, in addition to those developed by myositis patient support groups, deserve continued support to maintain the momentum in this field as they offer major opportunities to improve understanding of the pathogenesis and treatment of these diseases in cost-effective ways. PMID:25225838

Myositis registries and biorepositories: powerful tools to advance clinical, epidemiologic and pathogenic research.

PubMed

Rider, Lisa G; Dankó, Katalin; Miller, Frederick W

2014-11-01

Clinical registries and biorepositories have proven extremely useful in many studies of diseases, especially rare diseases. Given their rarity and diversity, the idiopathic inflammatory myopathies, or myositis syndromes, have benefited from individual researchers' collections of cohorts of patients. Major efforts are being made to establish large registries and biorepositories that will allow many additional studies to be performed that were not possible before. Here, we describe the registries developed by investigators and patient support groups that are currently available for collaborative research purposes. We have identified 46 myositis research registries, including many with biorepositories, which have been developed for a wide variety of purposes and have resulted in great advances in understanding the range of phenotypes, clinical presentations, risk factors, pathogenic mechanisms, outcome assessment, therapeutic responses, and prognoses. These are now available for collaborative use to undertake additional studies. Two myositis patient registries have been developed for research, and myositis patient support groups maintain demographic registries with large numbers of patients available to be contacted for potential research participation. Investigator-initiated myositis research registries and biorepositories have proven extremely useful in understanding many aspects of these rare and diverse autoimmune diseases. These registries and biorepositories, in addition to those developed by myositis patient support groups, deserve continued support to maintain the momentum in this field as they offer major opportunities to improve understanding of the pathogenesis and treatment of these diseases in cost-effective ways.

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

PubMed

Hering, Dagmara; Trzebski, Andrzej; Narkiewicz, Krzysztof

2017-03-01

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

Major clinical research advances in gynecologic cancer in 2015

PubMed Central

2016-01-01

In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7–9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review. PMID:27775259

Major clinical research advances in gynecologic cancer in 2015.

PubMed

Suh, Dong Hoon; Kim, Miseon; Kim, Hak Jae; Lee, Kyung Hun; Kim, Jae Weon

2016-11-01

In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7-9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review.

Advance directives: survey of primary care patients.

PubMed

O'Sullivan, Rory; Mailo, Kevin; Angeles, Ricardo; Agarwal, Gina

2015-04-01

To establish the prevalence of patients with advance directives in a family practice, and to describe patients' perspectives on a family doctor's role in initiating discussions about advance directives. A self-administered patient questionnaire. A busy urban family medicine teaching clinic in Hamilton, Ont. A convenience sample of adult patients attending the clinic over the course of a typical business week. The prevalence of advance directives in the patient population was determined, and the patients' expectations regarding the role of their family doctors were elucidated. The survey population consisted of 800 participants (a response rate of 72.5%) well distributed across age groups; 19.7% had written advance directives and 43.8% had previously discussed the topic of advance directives, but only 4.3% of these discussions had occurred with family doctors. In 5.7% of cases, a family physician had raised the issue; 72.3% of respondents believed patients should initiate the discussion. Patients who considered advance directives extremely important were significantly more likely to want their family doctors to start the conversation (odds ratio 3.98; P < .05). Advance directives were not routinely addressed in the family practice. Most patients preferred to initiate the discussion of advance directives. However, patients who considered the subject extremely important wanted their family doctors to initiate the discussion. Copyright© the College of Family Physicians of Canada.

Clinical and Cost Implications of Universal Versus Locally Advanced-Stage and Advanced-Stage-Only Molecular Testing for Epidermal Growth Factor Receptor Mutations and Anaplastic Lymphoma Kinase Rearrangements in Non-Small Cell Lung Carcinoma: A Tertiary Academic Institution Experience.

PubMed

Sauter, Jennifer L; Butnor, Kelly J

2016-04-01

Although epidermal growth factor receptor (EGFR)- and anaplastic lymphoma kinase (ALK)-directed therapies are not approved for patients with early-stage non-small cell lung carcinoma (NSCLC), many institutions perform EGFR and ALK testing for all patients with NSCLC at the time of initial diagnosis. Current consensus guidelines recommend EGFR testing and suggest ALK testing at the time of initial diagnosis for patients with advanced disease. To examine the cost and clinical impact of EGFR and ALK testing of patients with early-stage NSCLC. Records from all patients with a diagnosis of NSCLC made on a nonresection specimen at our institution during a single calendar year (2012) were reviewed, and a cost analysis was performed. Of 133 total patients, 47 (35%) had early-stage (stage I or II) disease and 86 (65%) had locally advanced (stage III) or advanced (stage IV) disease at presentation. Eight of 47 patients with early-stage disease (17%) had progression/recurrence during 18 to 30 months of follow-up, 6 of 8 (75%) of whom had pathologic confirmation of progression/recurrence. The estimated additional cost of EGFR and ALK testing for all newly diagnosed patients with NSCLC at our institution is $75,200 per year, compared to testing only patients with locally advanced and advanced-stage disease. The cost of universal molecular testing of NSCLC is substantial. EGFR and ALK testing of patients with early-stage disease appears to have negligible clinical impact, as most patients do not have disease recurrence/progression. Those whose disease recurs/progresses typically undergo rebiopsy. Our findings do not support the practice of universal EGFR and ALK testing in NSCLC at the time of initial diagnosis.

Clinical applications of advanced rotational radiation therapy

NASA Astrophysics Data System (ADS)

Nalichowski, Adrian

Purpose: With a fast adoption of emerging technologies, it is critical to fully test and understand its limits and capabilities. In this work we investigate new graphic processing unit (GPU) based treatment planning algorithm and its applications in helical tomotherapy dose delivery. We explore the limits of the system by applying it to challenging clinical cases of total marrow irradiation (TMI) and stereotactic radiosurgery (SRS). We also analyze the feasibility of alternative fractionation schemes for total body irradiation (TBI) and TMI based on reported historical data on lung dose and interstitial pneumonitis (IP) incidence rates. Methods and Materials: An anthropomorphic phantom was used to create TMI plans using the new GPU based treatment planning system and the existing CPU cluster based system. Optimization parameters were selected based on clinically used values for field width, modulation factor and pitch. Treatment plans were also created on Eclipse treatment planning system (Varian Medical Systems Inc, Palo Alto, CA) using volumetric modulated arc therapy (VMAT) for dose delivery on IX treatment unit. A retrospective review was performed of 42 publications that reported IP rates along with lung dose, fractionation regimen, dose rate and chemotherapy. The analysis consisted of nearly thirty two hundred patients and 34 unique radiation regimens. Multivariate logistic regression was performed to determine parameters associated with IP and establish does response function. Results: The results showed very good dosimetric agreement between the GPU and CPU calculated plans. The results from SBRT study show that GPU planning system can maintain 90% target coverage while meeting all the constraints of RTOG 0631 protocol. Beam on time for Tomotherapy and flattening filter free RapidArc was much faster than for Vero or Cyberknife. Retrospective data analysis showed that lung dose and Cyclophosphomide (Cy) are both predictors of IP in TBI/TMI treatments. The

[Physicochemical stability study of injectable solutions of cisatracurium besilate in clinical conditions].

PubMed

Pignard, J; Bourdeaux, D; Kauffmann, S; Constantin, J M; Sautou, V

2014-05-01

To assess the stability of cisatracurium besilate solution stored at 5°C and 25°C. Cisatracurium solutions at 2, 5 and 0.1mg/mL in 0.9 % sodium chloride or 5 % glucose were exposed to 5°C and 25°C under 60 % relative humidity for seven days. The physicochemical stability was assessed at 24, 48hours and seven days with dosage of the active substance, detection of degradation products and a possible racemization, measuring pH, osmolality and turbidity, assessment of coloration, visible particles and invisible particles count. Cisatracurium besilate present good stability for 24hours at 5°C and 25°C for concentrations between 0.1 and 5mg/mL. Beyond 24hours, the solutions at 2 and 5mg/mL remained stable for seven days at 5°C. At 25°C, potentially toxic degradation products appear in solutions of 0.1mg/mL between 24 and 48hours. No racemization was detected, the drug remains in its active form cis. Cisatracurium solutions at 2 and 5mg/mL may be stored at 5°C or 25°C for seven days. It's advisable to keep the solutions in a dilution of 0.1mg/mL in 0.9 % sodium chloride or 5 % glucose in the refrigerator. No diluted solution should be stored at room temperature beyond 24hours. Copyright © 2014 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

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

PubMed

Ahaghotu, Chiledum; Tyler, Robert; Sartor, Oliver

2016-04-01

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

A Second Opinion: A Case Narrative on Clinical Ethics Mediation.

PubMed

Weinstein, Michael S

2015-01-01

Contrasting traditional and common forms of ethics consultation with bioethics mediation, I describe the case of a "second opinion" consultation in the care of a patient with advanced cancer for whom treatment was futile. While the initial ethics consultation, performed by a colleague, led to a recommendation that some may deem ethical, the process failed to involve key stakeholders and failed to explore the underlying values and reasons for the opinions voiced by various stakeholders. The process of mediation ultimately led to creative solutions in which all stakeholders could reach consensus on a plan of care. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

An Academic-Business Partnership for Advancing Clinical Informatics.

ERIC Educational Resources Information Center

Connors, Helen R.; Weaver, Charlotte; Warren, Judith; Miller, Karen L.

2002-01-01

A partnership between a university school of nursing and a health care information technology supplier resulted in the Simulated E-hEalth Delivery System (SEEDS). This program enables nursing students to learn clinical skills in a state-of-the-art environment using a live-production, clinical information system designed for care delivery. (JOW)

[Recent advance in chemotherapy for advanced colorectal cancer].

PubMed

Aiba, K

1996-04-01

Chemotherapy for advanced colorectal cancer is reviewed stressing the historical development of combination chemotherapy and the application of a new idea called biochemical modulation based upon a preclinical biochemical and molecular pharmacological rationale. While 5-fluorouracil (5-FU) is a key drug for more than three decades, many a combination chemotherapy with 5-FU and other drugs such as methyl-CCNU, vincristine, streptozocin, mitomycin C and so on has been studied extensively only to show no significant improvement compared with monotherapy with 5-FU. Recently, the mechanisms of 5-FU action have been recognized more in detail biochemically, and it enabled us to try the drug in a more optimal way. For example, bolus i.v. infusion of 5-FU can produce a response rate of around 10% to 15% at most for advanced colorectal cancer. On the other hand, a more continuous mode of i.v. infusion, typically known as protracted i.v. infusion lasting up to 6 weeks or more, can produce the response rate of up to 40%. The difference underlying the mechanisms of action in these typical two administrative methods is that the main target can be RNA-directed cytotoxicity in the bolus type infusion and it can be shifted toward DNA-directed cytotoxicity in the continuous type infusion through the inhibition of thymidylate synthase (TS) enzyme activity which is relevant to DNA de novo synthesis. More importantly, investigations using clinical materials imply that DNA-directed cytotoxicity may be more relevant in a clinical setting, showing consistent findings between bench-top experiments and the clinical outcome. Given a precise knowledge about the mechanisms of 5-FU action, we could have developed a new type combination chemotherapy called biochemical modulation which manipulates non-cytotoxic agents or cytotoxic agents in non-cytotoxic level as modulators enhancing cytotoxicity of 5-FU biochemically. Among modulators, leucovorin (LV) has been shown to have a pivotal role in

X-ray phase-contrast imaging of the breast—advances towards clinical implementation

PubMed Central

Herzen, J; Willner, M; Grandl, S; Scherer, K; Bamberg, F; Reiser, M F; Pfeiffer, F; Hellerhoff, K

2014-01-01

Breast cancer constitutes about one-quarter of all cancers and is the leading cause of cancer death in women. To reduce breast cancer mortality, mammographic screening programmes have been implemented in many Western countries. However, these programmes remain controversial because of the associated radiation exposure and the need for improvement in terms of diagnostic accuracy. Phase-contrast imaging is a new X-ray-based technology that has been shown to provide enhanced soft-tissue contrast and improved visualization of cancerous structures. Furthermore, there is some indication that these improvements of image quality can be maintained at reduced radiation doses. Thus, X-ray phase-contrast mammography may significantly contribute to advancements in early breast cancer diagnosis. Feasibility studies of X-ray phase-contrast breast CT have provided images that allow resolution of the fine structure of tissue that can otherwise only be obtained by histology. This implies that X-ray phase-contrast imaging may also lead to the development of entirely new (micro-) radiological applications. This review provides a brief overview of the physical characteristics of this new technology and describes recent developments towards clinical implementation of X-ray phase-contrast imaging of the breast. PMID:24452106

Delineating advanced practice nursing in New Zealand: a national survey.

PubMed

Carryer, J; Wilkinson, J; Towers, A; Gardner, G