Foundational biomedical informatics research in the clinical and translational science era: a call to action.

PubMed

Payne, Philip R O; Embi, Peter J; Niland, Joyce

2010-01-01

Advances in clinical and translational science, along with related national-scale policy and funding mechanisms, have provided significant opportunities for the advancement of applied clinical research informatics (CRI) and translational bioinformatics (TBI). Such efforts are primarily oriented to application and infrastructure development and are critical to the conduct of clinical and translational research. However, they often come at the expense of the foundational CRI and TBI research needed to grow these important biomedical informatics subdisciplines and ensure future innovations. In light of this challenge, it is critical that a number of steps be taken, including the conduct of targeted advocacy campaigns, the development of community-accepted research agendas, and the continued creation of forums for collaboration and knowledge exchange. Such efforts are needed to ensure that the biomedical informatics community is able to advance CRI and TBI science in the context of the modern clinical and translational science era.

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 their transition to new roles. © 2015 John Wiley & Sons Ltd.

Novel drugs in clinical development for hepatocellular carcinoma.

PubMed

Waidmann, Oliver; Trojan, Jörg

2015-01-01

Sorafenib is the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). Within recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development either due to toxicity or lack of benefit. This review covers recent clinical data on systemic agents and ongoing trials in patients with advanced HCC. In unselected patients with advanced HCC, disappointing results have been reported from several large trials. However, in two subgroups encouraging results have been achieved. Treatment with the MET inhibitor tivantinib resulted in a substantial survival benefit in the subgroup of MET overexpressing tumors in a randomized Phase II trial. Furthermore, the vascular endothelial growth factor receptor 2 antibody ramucirumab resulted in improved overall survival in patients with baseline α-fetoprotein (AFP) ≥ 400 ng/ml in a Phase III trial. These two agents, and several others, will be further developed in HCC. Moreover, immunotherapeutics such as checkpoint inhibitors, programmed death receptor-1 blocking antibodies and oncolytic viruses are under investigation in advanced HCC.

The Role of Research in Advanced Dental Education.

ERIC Educational Resources Information Center

Profitt, William R.; Vig, Peter S.

1980-01-01

Even though research is an integral part of quality advanced dental programs, many dental departments with postdoctoral programs lack faculty and other resources for research productivity. Programs to produce clinical faculty with research training are called for through the development of clinical research centers. (JSR)

Implementation of a pharmacist career ladder program.

PubMed

Heavner, Mojdeh S; Tichy, Eric M; Yazdi, Marina

2016-10-01

The implementation and outcomes of a pharmacist career ladder program (PCLP) at a tertiary care, academic medical center are described. A PCLP was developed at Yale-New Haven Hospital to guide career development, motivate staff to perform beyond their daily tasks and responsibilities, and recognize and retain high performers through professional advancement. The PCLP advancement criteria include specific requirements for excellence in five categories: level of training and experience, pharmacy practice, drug information, education and scholarship, and leadership. The PCLP is designed with four distinct tiers: clinical pharmacist, clinical pharmacist II, clinical pharmacy specialist, and clinical pharmacy specialist II. The specific criteria are increasingly challenging to achieve when moving up the ladder. Pharmacists may apply voluntarily each year for advancement. A PCLP review committee consisting of pharmacist peers and managers meets annually to discuss and vote on career advancement decisions. Since PCLP implementation, we have observed an increasing success rate for advancement (50% in 2013, 85% in 2014, and 100% in 2015) and a considerable increase in pharmacist participation in clinical and process improvement projects, as well as intervention and medication-use variance documentation. The implementation of a PCLP at a tertiary care, academic medical center provided an opportunity for frontline pharmacists to advance professionally and increased their participation and leadership in clinical and process improvement projects and drug-use policy and medication safety initiatives; the program also increased the number of pharmacists with specialty board certification and peer-reviewed publications. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Advanced Critical Care Practitioners - Practical experience of implementing the Advanced Critical Care Practitioner Faculty of Intensive Care Medicine Curriculum in a London Critical Care Unit.

PubMed

Lee, Geraldine; Gilroy, Jo-Anne; Ritchie, Alistair; Grover, Vimal; Gull, Keetje; Gruber, Pascale

2018-05-01

With a chronic shortage of doctors in intensive care, alternative roles are being explored. One of these is the role of the Advanced Critical Care Practitioner. The Advanced Critical Care Practitioner Curriculum was developed by the Faculty of Intensive Care Medicine and is used to provide a structured programme of training. The Advanced Critical Care Practitioner programme consists of an academic and clinical component. This article outlines a practical approach of how the programme was developed and is currently being delivered at a single institution. This new advanced practice role offers opportunities to fill gaps in the medical workforce, improve continuity of patient care, provide mentoring and training for less experienced staff as well as offering a rewarding clinical role.

Advances in anesthesia technology are improving patient care, but many challenges remain.

PubMed

John Doyle, D; Dahaba, Ashraf; LeManach, Yannick

2018-04-13

Although significant advances in clinical monitoring technology and clinical practice development have taken place in the last several decades, in this editorial we argue that much more still needs to be done. We begin by identifying many of the improvements in perioperative technology that have become available in recent years; these include electroencephalographic depth of anesthesia monitoring, bedside ultrasonography, advanced neuromuscular transmission monitoring systems, and other developments. We then discuss some of the perioperative technical challenges that remain to be satisfactorily addressed, such as products that incorporate poor software design or offer a confusing user interface. Finally we suggest that the journal support initiatives to help remedy this problem by publishing reports on the evaluation of medical equipment as a means to restore the link between clinical research and clinical end-users.

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

The Development of a Postgraduate Orthopaedic Manual Therapy Residency Program in Nairobi, Kenya.

PubMed

Cunningham, Shala; Jackson, Richard; Muli, Daniel Kangutu; McFelea, Joni

2017-01-01

There are very few opportunities for long-term, comprehensive postgraduate education in developing countries because of fiscal and human resource constraints. Therefore, physiotherapists have little opportunity following graduation to advance their skills through the improvement of clinical reasoning and treatment planning and application. To address the need for sustainable advanced instruction in physiotherapy within the country, a postgraduate Residency program was initiated in Nairobi, Kenya in 2012. The mission of the program is to graduate advanced orthopedic practitioners who can lead their communities and local profession in the advancement of clinical care and education. Since its inception, six cohorts have been initiated for a total of 90 resident participants. In addition, six program graduates are being trained to continue the Residency program and are serving as teaching assistants for the on campus modules. This training will result in a self-sustaining program by 2020. The manual therapy Residency education model allowed for advancement of the participating physiotherapists professional development utilizing evidence-based practice. This was done without altering the current education system within the country, or accessing expensive equipment. The Residency program was developed and established with the cooperation of a local education institution and a non-profit corporation in the United States. This collaboration has facilitated the advancement of orthopedic clinical standards in the country and will, hopefully, one day serve an as a template for future programs.

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

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 neuropsychology in South Korea.

PubMed

Kim, Myung-Sun; Chey, Jeanyung

2016-11-01

Clinical neuropsychology in South Korea, albeit its relatively short history, has advanced dramatically. We review a brief history and current status of clinical neuropsychology in South Korea. The history, the educational pathway, the training pathway, the certification process, and careers in clinical neuropsychology in South Korea are reviewed. We have reviewed the neuropsychological services, including assessment and treatment, research on neurological and psychiatric populations, and neuropsychology education and the requirements related to education, training, and board examinations of those providing neuropsychological services in South Korea. We also describe how the Korean Society for Neuropsychology Research, the first and only meeting for neuropsychologists in the country established in 1999, has played a major role in how clinical neuropsychology is practiced and developed as a professional field in South Korea. Clinical neuropsychology in South Korea has achieved major progress over just a quarter of a century, and its future is promising in light of the increasing demand for neuropsychological services and advances in neuroscience in the country. Challenges that the community of clinical neuropsychologists are currently facing in South Korea, including formalizing neuropsychological curriculum and training programs and developing advanced credentialing procedures, are discussed.

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

Regulation of immunotherapeutic products for cancer and FDA’s role in product development and clinical evaluation

PubMed Central

2013-01-01

Immunotherapeutics include drugs and biologics that render therapeutic benefit by harnessing the power of the immune system. The promise of immune-mediated therapies is target specificity with a consequent reduction in off-target side effects. Recent scientific advances have led to clinical trials of both active and passive immunotherapeutic products that have the potential to convert life-ending diseases into chronic but manageable conditions. Clinical trials investigating immunotherapeutics are ongoing with some trials at advanced stages of development. However, as with many products involving novel mechanisms of action, major regulatory and scientific issues arising with clinical use of immunotherapeutic products remain to be addressed. In this review, we address issues related to different immunotherapeutics and provide recommendations for the characterization and evaluation of these products during various stages of product and clinical development. PMID:24764535

Engaging Clinical Nurses in Quality Improvement Projects.

PubMed

Moore, Susan; Stichler, Jaynelle F

2015-10-01

Clinical nurses have the knowledge and expertise required to provide efficient and proficient patient care. Time and knowledge deficits can prevent nurses from developing and implementing quality improvement or evidence-based practice projects. This article reviews a process for professional development of clinical nurses that helped them to define, implement, and analyze quality improvement or evidence-based practice projects. The purpose of this project was to educate advanced clinical nurses to manage a change project from inception to completion, using the Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) Change Acceleration Process as a framework. One-to-one mentoring and didactic in-services advanced the knowledge, appreciation, and practice of advanced practice clinicians who completed multiple change projects. The projects facilitated clinical practice changes, with improved patient outcomes; a unit cultural shift, with appreciation of quality improvement and evidence-based projects; and engagement with colleagues. Project outcomes were displayed in poster presentations at a hospital exposition for knowledge dissemination. Copyright 2015, SLACK Incorporated.

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.

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.

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

Advanced practice nurses' scope of practice: a qualitative study of advanced clinical competencies.

PubMed

Nieminen, Anna-Lena; Mannevaara, Bodil; Fagerström, Lisbeth

2011-12-01

To describe and explore Advanced Practice Nurses' clinical competencies and how these are expressed in clinical practice. Discussion concerning advanced clinical practice has been ongoing in the USA since the 1960s and in the UK since the late 1980s. Approximately 24 countries, excluding the USA, have implemented the role of Advance Practice Nurse (APN). In the Nordic countries, especially Sweden and Finland, APNs have been introduced in some organizations but their competency domains have not yet been clearly defined. The study's theoretical framework emanates from Aristotle's three-dimensional view of knowledge that is epistêmê, technê, and phronesis. Between October 2005 and January 2006, focus group interviews of Clinical Nurse Specialists who provide expert functions in pediatric, internal medicine, and surgical units (n = 26) and APN students (n = 8) were conducted. The data material was analyzed using inductive content analysis. Grouped into five main themes, the study results indicate that APNs possess advanced level clinical competencies in: (A) assessment of patients' caring needs and nursing care activities, (B) the caring relationship, (C) multi-professional teamwork, (D) development of competence and nursing care, and (E) leadership in a learning and caring culture. Clinical competencies consist of advanced skills, which typify an expanding role that offers new possibilities for holistic patient care practice. APNs' scope of practice is characterized by responsibility and competence in making autonomous judgments based on expanded clinical competence. On an advanced level, clinical competence consists not merely of advanced skills for assessing and meeting the needs of patients but also the creation of safe and trustful relationships with patients and collaboration with colleagues. APNs can realize advanced skills in their actions through their manner of knowing, doing, and being. © 2011 The Authors. Scandinavian Journal of Caring Sciences © 2011 Nordic College of Caring Science.

Factors influencing advanced practitioners' ability to enact leadership: a case study within Irish healthcare.

PubMed

Higgins, Agnes; Begley, Cecily; Lalor, Joan; Coyne, Imelda; Murphy, Kathy; Elliott, Naomi

2014-10-01

To report the factors that influence clinical specialists' and advanced nurse practitioners' ability to enact their clinical and professional leadership roles; findings from the SCAPE study. The importance of leadership for specialist and advanced practitioners is highlighted in the international literature and is considered an important factor in the provision of improved patient outcomes. Despite many studies identifying the barriers in developing and integrating new specialist/advanced practice roles into health services, little is known about the factors that influence the leadership dimension of their role. A case study design involving 23 clinical specialist/advanced practitioners working in Ireland and multidisciplinary team members working with them, was used. Data were collected using interview, observation and documentary analysis. Four mediating factors influence the specialist/advanced practitioner's ability to perform a leadership role, namely the presence of a framework for the professional development of the role; opportunities to act as leaders; mechanisms for sustaining leadership; and personal attributes of practitioners. Nursing/midwifery leaders and managers at all levels have a key role in supporting leadership potential, through countering the negative impact of professional isolation, expanding opportunities for specialist/advanced practitioners to influence policy and network with wider professional groups. © 2013 John Wiley & Sons Ltd.

Development of a video-based education and process change intervention to improve advance cardiopulmonary resuscitation decision-making.

PubMed

Waldron, Nicholas; Johnson, Claire E; Saul, Peter; Waldron, Heidi; Chong, Jeffrey C; Hill, Anne-Marie; Hayes, Barbara

2016-10-06

Advance cardiopulmonary resuscitation (CPR) decision-making and escalation of care discussions are variable in routine clinical practice. We aimed to explore physician barriers to advance CPR decision-making in an inpatient hospital setting and develop a pragmatic intervention to support clinicians to undertake and document routine advance care planning discussions. Two focus groups, which involved eight consultants and ten junior doctors, were conducted following a review of the current literature. A subsequent iterative consensus process developed two intervention elements: (i) an updated 'Goals of Patient Care' (GOPC) form and process; (ii) an education video and resources for teaching advance CPR decision-making and communication. A multidisciplinary group of health professionals and policy-makers with experience in systems development, education and research provided critical feedback. Three key themes emerged from the focus groups and the literature, which identified a structure for the intervention: (i) knowing what to say; (ii) knowing how to say it; (iii) wanting to say it. The themes informed the development of a video to provide education about advance CPR decision-making framework, improving communication and contextualising relevant clinical issues. Critical feedback assisted in refining the video and further guided development and evolution of a medical GOPC approach to discussing and recording medical treatment and advance care plans. Through an iterative process of consultation and review, video-based education and an expanded GOPC form and approach were developed to address physician and systemic barriers to advance CPR decision-making and documentation. Implementation and evaluation across hospital settings is required to examine utility and determine effect on quality of care.

Training and career development in clinical and translational science: an opportunity for rehabilitation scientists.

PubMed

Kelly, Thomas H; Mattacola, Carl G

2010-11-01

The National Institutes of Health's Clinical and Translational Science Award initiative is designed to establish and promote academic centers of clinical and translational science (CTS) that are empowered to train and advance multi- and interdisciplinary investigators and research teams to apply new scientific knowledge and techniques to enhance patient care. Among the key components of a full-service center for CTS is an educational platform to support research training in CTS. Educational objectives and resources available to support the career development of the clinical and translational scientists, including clinical research education, mentored research training, and career development support, are described. The purpose of the article is to provide an overview of the CTS educational model so that rehabilitation specialists can become more aware of potential resources that are available and become more involved in the delivery and initiation of the CTS model in their own workplace. Rehabilitation clinicians and scientists are well positioned to play important leadership roles in advancing the academic mission of CTS. Rigorous academic training in rehabilitation science serves as an effective foundation for supporting the translation of basic scientific discovery into improved health care. Rehabilitation professionals are immersed in patient care, familiar with interdisciplinary health care delivery, and skilled at working with multiple health care professionals. The NIH Clinical and Translational Science Award initiative is an excellent opportunity to advance the academic development of rehabilitation scientists.

Important advances in technology and unique applications related to cardiac magnetic resonance imaging.

PubMed

Ghosn, Mohamad G; Shah, Dipan J

2014-01-01

Cardiac magnetic resonance has become a well-established imaging modality and is considered the gold standard for myocardial tissue viability assessment and ventricular volumes quantification. Recent technological hardware and software advancements in magnetic resonance imaging technology have allowed the development of new methods that can improve clinical cardiovascular diagnosis and prognosis. The advent of a new generation of higher magnetic field scanners can be beneficial to various clinical applications. Also, the development of faster acquisition techniques have allowed mapping of the magnetic relaxation properties T1, T2, and T2* in the myocardium that can be used to quantify myocardial diffuse fibrosis, determine the presence of edema or inflammation, and measure iron within the myocardium, respectively. Another recent major advancement in CMR has been the introduction of three-dimension (3D) phase contrast imaging, also known as 4D flow. The following review discusses key advances in cardiac magnetic resonance technology and their potential to improve clinical cardiovascular diagnosis and outcomes.

Advances in diagnostic and treatment modalities for intracranial tumors.

PubMed

Dickinson, P J

2014-01-01

Intracranial neoplasia is a common clinical condition in domestic companion animals, particularly in dogs. Application of advances in standard diagnostic and therapeutic modalities together with a broad interest in the development of novel translational therapeutic strategies in dogs has resulted in clinically relevant improvements in outcome for many canine patients. This review highlights the status of current diagnostic and therapeutic approaches to intracranial neoplasia and areas of novel treatment currently in development. Copyright © 2014 by the American College of Veterinary Internal Medicine.

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 debate on the development of advanced competences].

PubMed

Dimonte, Valerio; Palese, Alvisa; Chiari, Paolo; Laquintana, Dario; Tognoni, Gianni; Di Giulio, Paola

2016-01-01

. The debate on the development of advanced nursing competences. The dossier aims to describe and disentagle the present Italian and international debate on the development and recognition of advanced nursing competences. Following a general brief description of the legislative national background, the attention is first of all focused on the lack of clarity on the definition of advanced competence, which is further complicated by the issue of their formal, contractual and economic recognition. To explore these issues a list of contributions is presented and some proposals are formulated to favor a better oriented development of the debate: a. A convenience sample of 139 nurses were interviewed asking to describe problems occurred in the last month that could prompt the intervention of an expert nurse and to list the clinical, managerial and educational competences of a specialized nurse in their ward. The results document the quality and the dispersion of the definitions which are perceived and applied in the general settings of care. b. The issue the post basic courses (master, specialization) offered to nurses in 2015-2016 by Italian universities were described and their aims. While the contribution of the courses in increasing the theoretical knowledge is well defined, the aims and the description of the clinical training are badly developed and an acquisition of advanced competences would seem unlikely. c. The definition of advanced competences was explored in the international literature: while evidences are available on the impact of advanced nursing on patients' outcomes, what is advanced nursing is far from being clear, and an impressive list of roles, activities and functions are considered advanced. d. Although at national level there is no formal recognition for nurses with advanced competences (with the exception of the head nurse that holds mostly an organizational rather than clinical role), the opportunities for promoting the role of specialistic/advanced nurses were described. An interview to 20 nursing managers representing 23 Italian hospitals and districts shows the huge variability of what is recognized and considered specialistic/advanced competence. Competences in stoma care, venous catheters, pressure sores, do not necessarily cover the concept of advanced competence. e. Two further contributions explore how the challenge of what is ill-defined (or cannot be defined) can be transformed in a methodological opportunity and how the growth of an health profession may break the delicate balance of the boundaries between professions.

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

PubMed

Wagholikar, Amol; Fung, Maggie; Nelson, Colleen

2011-01-01

To understand the journey of advanced prostate cancer patients for supporting development of an innovative patient journey browser. Prostate cancer is one of the common cancers in Australia. Due to the chronic nature of the disease, it is important to have effective disease management strategy and care model. Multi-disciplinary care is a well-proven approach for chronic disease management. The Multi-disciplinary team (MDT) can function more effectively if all the required information is available for the clinical decision support. The development of innovative technology relies on an accurate understanding of the advanced prostate cancer patient's journey over a prolonged period. This need arises from the fact that advanced prostate cancer patients may follow various treatment paths and change their care providers. As a result of this, it is difficult to understand the actual sources of patient's clinical records and their treatment patterns. The aim of the research is to understand variable sources of clinical records, treatment patterns, alternative therapies, over the counter (OTC) medications of advanced prostate cancer patients. This study provides better and holistic understanding of advanced prostate cancer journey. The study was conducted through an on-line survey developed to seek and analyse the responses from the participants. The on-line questionnaire was carefully developed through consultations with the clinical researchers at the Australian Prostate Cancer Research Centre-Queensland, prostate cancer support group representatives and health informaticians at the Australian E-Health Research Centre. The non-identifying questionnaire was distributed to the patients through prostate cancer support groups in Queensland, Australia. The pilot study was carried out between August 2010 and December 2010. The research made important observations about the advanced prostate cancer journey. It showed that General Practitioner (GP) was the common source of 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.

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.

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

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

An Internationally Consented Standard for Nursing Process-Clinical Decision Support Systems in Electronic Health Records.

PubMed

Müller-Staub, Maria; de Graaf-Waar, Helen; Paans, Wolter

2016-11-01

Nurses are accountable to apply the nursing process, which is key for patient care: It is a problem-solving process providing the structure for care plans and documentation. The state-of-the art nursing process is based on classifications that contain standardized concepts, and therefore, it is named Advanced Nursing Process. It contains valid assessments, nursing diagnoses, interventions, and nursing-sensitive patient outcomes. Electronic decision support systems can assist nurses to apply the Advanced Nursing Process. However, nursing decision support systems are missing, and no "gold standard" is available. The study aim is to develop a valid Nursing Process-Clinical Decision Support System Standard to guide future developments of clinical decision support systems. In a multistep approach, a Nursing Process-Clinical Decision Support System Standard with 28 criteria was developed. After pilot testing (N = 29 nurses), the criteria were reduced to 25. The Nursing Process-Clinical Decision Support System Standard was then presented to eight internationally known experts, who performed qualitative interviews according to Mayring. Fourteen categories demonstrate expert consensus on the Nursing Process-Clinical Decision Support System Standard and its content validity. All experts agreed the Advanced Nursing Process should be the centerpiece for the Nursing Process-Clinical Decision Support System and should suggest research-based, predefined nursing diagnoses and correct linkages between diagnoses, evidence-based interventions, and patient outcomes.

Recent advances in pacemaker and implantable defibrillator therapy for young patients.

PubMed

Walsh, Edward P; Cecchin, Frank

2004-03-01

This review is intended to highlight major clinical advances over the past year related to (1). biventricular pacing as a treatment for dilated myopathy, (2). growing clinical experience with implantable cardioverter defibrillators in pediatrics, (3). technical advances in standard antibradycardia pacing, and (4). an appraisal of the newly updated ACC/AHA/NASPE guidelines for device implant in children and adolescents. Complex rhythm devices are being used more frequently in children. Biventricular pacing to improve ventricular contractility is a rapidly evolving technology that has now been applied to children and young adults with intraventricular conduction delay, such as bundle branch block after cardiac surgery. Implantable defibrillators are also being used for an expanding list of conditions, although lead dysfunction is seen as a fairly common complication in active young patients. Guidelines for device implantation have been developed, but the weight of evidence remains somewhat limited by the paucity of pediatric data in this field. Thanks to refinements in lead design and generator technology, coupled with rapidly expanding clinical indications, pacemakers and implantable defibrillators have become increasingly important components of cardiac therapy for young patients. Expanded multicenter clinical studies will be needed to develop more objective guidelines for use of this advanced technology.

Assessing Clinical Research Capacity in Vietnam: A Framework for Strengthening Capability for Clinical Trials in Developing Countries.

PubMed

Kagan, Jonathan; Giang, Dao Duc; Iademarco, Michael F; Phung, Van Tt; Lau, Chuen-Yen; Quang, Nguyen Ngo

2016-01-01

Although improving health systems promises important benefits, most developing nations lack the resources to support nationally driven clinical research. Strengthened clinical research capacity can advance national health goals by supporting greater autonomy in aligning research with national priorities. From March through June 2010, we assessed six elements of clinical research capacity in Vietnam: research agenda; clinical investigators and biostatisticians; donors and sponsors; community involvement; scientific, ethical, safety, and quality oversight; and clinical research institutions. Assessments were drawn from interviews with investigators, Ministry of Health staff members, nongovernment organizations, and U.S. Mission staff members, and document review. Observations and recommendations were shared with collaborators. Reassessment in 2015 found growth in the number of clinical trials, improved regulation in human subjects protection and community engagement, and modest advances in research agenda setting. Training and investment in institutions remain challenging. A framework for assessing clinical research capacity can affirm strengths and weaknesses and guide the coordination of capacity-building efforts.

Win-win-win: collaboration advances critical care practice.

PubMed

Spence, Deb; Fielding, Sandra

2002-10-01

Against a background of increasing interest in education post registration, New Zealand nurses are working to advance their professional practice. Because the acquisition of highly developed clinical capabilities requires a combination of nursing experience and education, collaboration between clinicians and nurse educators is essential. However, the accessibility of relevant educational opportunities has been an ongoing issue for nurses outside the country's main centres. Within the framework of a Master of Health Science, the postgraduate certificate (critical care nursing) developed between Auckland University of Technology and two regional health providers is one such example. Students enrol in science and knowledge papers concurrently then, in the second half of the course, are supported within their practice environment to acquire advanced clinical skills and to analyse, critique and develop practice within their specialty. This paper provides an overview of the structure and pr month, distance education course focused on developing the context of critical care nursing.

The Vanderbilt Professional Nursing Practice Program, part 3: managing an advancement process.

PubMed

Steaban, Robin; Fudge, Mitzie; Leutgens, Wendy; Wells, Nancy

2003-11-01

Consistency of performance standards across multiple clinical settings is an essential component of a credible advancement system. Our advancement process incorporates a central committee, composed of nurses from all clinical settings within the institution, to ensure consistency of performance in inpatient, outpatient, and procedural settings. An analysis of nurses advanced during the first 18 months of the program indicates that performance standards are applicable to nurses in all clinical settings. The first article (September 2003) in this 3-part series described the foundation for and the philosophical background of the Vanderbilt Professional Nursing Practice Program (VPNPP), the career advancement program underway at Vanderbilt University Medical Center. Part 2 described the development of the evaluation tools used in the VPNPP, the implementation and management of this new system, program evaluation, and improvements since the program's inception. The purpose of this article is to review the advancement process, review the roles of those involved in the process, and to describe outcomes and lessons learned.

Emerging Trends in Clinical Research: With Implications for Population Health and Health Policy.

PubMed

Chin-Yee, Benjamin; Subramanian, S V; Verma, Amol A; Laupacis, Andreas; Razak, Fahad

2018-06-01

Policy Points: Significant advances in clinical medicine that have broader societal relevance may be less accessible to population health researchers and policymakers because of increased specialization within fields. We describe important recent clinical advances and discuss their broader societal impact. These advances include more expansive strategies for disease prevention, the rise of precision medicine, applications of human microbiome research, and new and highly successful treatments for hepatitis C infection. These recent developments in clinical research raise important issues surrounding health care costs and equitable resource allocation that necessitate an ongoing dialogue among the fields of clinical medicine, population health, and health policy. Developments in clinical medicine have important implications for population health, and there is a need for interdisciplinary engagement among clinical medicine, the social sciences, and public health research. The aim of this article is to help bridge the divide between these fields by exploring major recent advances in clinical medicine that have important implications for population health. We reviewed the most cited articles published from 2010 to 2015 in 5 high-impact clinical journals and selected 5 randomized controlled trials and 2 related clinical practice guidelines that are broadly relevant to population health and policy. We discuss the following themes: (1) expanding indications for drug therapy and the inherent medicalization of the population as highlighted by studies and clinical guidelines supporting lower blood pressure targets or widespread statin use; (2) the tension in nutritional research between quantifying the impact of isolated nutrients and studying specific foods and dietary patterns, for example, the role of the Mediterranean diet in the primary prevention of cardiovascular disease; (3) the issue of high medication costs and the challenge of providing equitable access raised by the development of new and effective treatments for hepatitis C infection; (4) emerging clinical applications of research on the human microbiome as illustrated by fecal transplant to treat Clostridium difficile infections; and (5) the promise and limitations of precision medicine as demonstrated by the rise of novel targeted therapies in oncology. These developments in clinical science hold promise for improving individual and population health and raise important questions about resource allocation, the role of prevention, and health disparities. © 2018 Milbank Memorial Fund.

Emerging pathways and future targets for the molecular therapy of pancreatic cancer.

PubMed

Vaccaro, Vanja; Melisi, Davide; Bria, Emilio; Cuppone, Federica; Ciuffreda, Ludovica; Pino, Maria Simona; Gelibter, Alain; Tortora, Giampaolo; Cognetti, Francesco; Milella, Michele

2011-10-01

Pancreatic cancer treatment remains a challenge for clinicians and researchers. Despite undisputable advances in the comprehension of the molecular mechanisms underlying cancer development and progression, early disease detection and clinical management of patients has made little, if any, progress in the past 20 years. Clinical development of targeted agents directed against validated pathways, such as the EGF/EGF receptor axis, the mutant KRAS protein, MMPs, and VEGF-mediated angiogenesis, alone or in combination with gemcitabine-based standard chemotherapy, has been disappointing. This review explores the preclinical rationale for clinical approaches aimed at targeting the TGF-β, IGF, Hedgehog, Notch and NF-κB signaling pathways, to develop innovative therapeutic strategies for pancreatic cancer. Although some of the already clinically explored approaches (particularly EGFR and KRAS targeting) deserve further clinical consideration, by employing more innovative and creative clinical trial designs than the gemcitabine-targeted agent paradigm that has thus far invariably failed, the targeting of emerging and relatively unexplored signaling pathways holds great promise to increase our understanding of the complex molecular biology and to advance the clinical management of pancreatic cancer.

Development of InCVAX as a novel in situ autologous vaccine for metastatic cancers (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hode, Tomas; Alleruzzo, Luciano; Raker, Joseph; Lam, Samuel Siu Kit; Nordquist, Robert E.; Chen, Wei R.

2016-03-01

A novel method, an in situ autologous whole-cell cancer vaccine (inCVAX), is being developed by Immunophotonics, Inc., for the treatment of metastatic cancers. inCVAX combines phototherapy and immunotherapy to potentially induce a systemic anti-tumor immune response in the hosts. Immunophotonics and its academic partners have spent years conducting nonclinical research, developing CMC techniques and conducting clinical research. In 2015 the company initiated a late-stage (II/III) clinical trial in South America for advanced breast cancer patients. The process of developing the inCVAX approach from a laboratory setting into clinical trials requires significant efforts from a group of dedicated engineers, scientists, and physicians. The growth of the company and its business advances demonstrated the determination of a group of visionary investors, entrepreneurs, and business leaders. This talk will chronicle the milestones of the scientific achievement, medical progress, and business development of Immunophotonics.

[Evidence on chronic myeloproliferative neoplasms from landmark clinical trials].

PubMed

Yamaguchi, Hiroki

2015-08-01

Mutations in the JAK2 gene are thought to underlie the development of chronic myeloproliferative neoplasms (cMPN). Indeed, ≥95% of polycythemia vera patients, and half or more of essential thrombocythemia and primary myelofibrosis (PMF) patients, harbor the JAK2V617F mutation. Besides the JAK2V617F mutation, the JAK2 exon 12 deletion, the MPLW515L/K, and CALR mutation have been discovered and shown to be involved in the pathogenesis of these diseases. Based on these advancements in the study of cMPN, the JAK2 inhibitor was developed as a new therapy for PMF. Moreover, recent advancements in our ability to diagnose cMPN have paralleled the development of large clinical trials for patients with cMPN. This article provides explanatory information from these large clinical trials that is useful for the actual clinical practice of caring for patients with cMPN in Japan.

Immunotherapy for Ovarian Cancer: What's Next?

PubMed Central

Kandalaft, Lana E.; Powell, Daniel J.; Singh, Nathan; Coukos, George

2011-01-01

In the past decade, we have witnessed important gains in the treatment of ovarian cancer; however, additional advances are required to reduce mortality. With compelling evidence that ovarian cancers are immunogenic tumors, immunotherapy should be further pursued and optimized. The dramatic advances in laboratory and clinical procedures in cellular immunotherapy, along with the development of powerful immunomodulatory antibodies, create new opportunities in ovarian cancer therapeutics. Herein, we review current progress and future prospects in vaccine and adoptive T-cell therapy development as well as immunomodulatory therapy tools available for immediate clinical testing. PMID:21079136

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, thereby improving clinical outcomes and quality of care. With their emphasis on quality and safety, the eight competency domains also offer a framework for enhancing position descriptions, performance evaluations, clinical recognition, initial and ongoing competency assessment programs, and orientation and residency programs.

Blending technology in teaching advanced health assessment in a family nurse practitioner program: using personal digital assistants in a simulation laboratory.

PubMed

Elliott, Lydia; DeCristofaro, Claire; Carpenter, Alesia

2012-09-01

This article describes the development and implementation of integrated use of personal handheld devices (personal digital assistants, PDAs) and high-fidelity simulation in an advanced health assessment course in a graduate family nurse practitioner (NP) program. A teaching tool was developed that can be utilized as a template for clinical case scenarios blending these separate technologies. Review of the evidence-based literature, including peer-reviewed articles and reviews. Blending the technologies of high-fidelity simulation and handheld devices (PDAs) provided a positive learning experience for graduate NP students in a teaching laboratory setting. Combining both technologies in clinical case scenarios offered a more real-world learning experience, with a focus on point-of-care service and integration of interview and physical assessment skills with existing standards of care and external clinical resources. Faculty modeling and advance training with PDA technology was crucial to success. Faculty developed a general template tool and systems-based clinical scenarios integrating PDA and high-fidelity simulation. Faculty observations, the general template tool, and one scenario example are included in this article. ©2012 The Author(s) Journal compilation ©2012 American Academy of Nurse Practitioners.

Treating advanced non-small-cell lung cancer in Chinese patients: focus on icotinib

PubMed Central

Liang, Jun-Li; Ren, Xiao-Cang; Lin, Qiang

2014-01-01

Icotinib hydrochloride is an orally administered small-molecule reversible tyrosine kinase inhibitor that has been independently researched and developed and has independent intellectual property rights in the People’s Republic of China. Clinical trials have demonstrated that the response to icotinib among advanced non-small-cell lung cancer (NSCLC) patients who received at least one platinum-based chemotherapy regimen was not inferior to gefitinib. Since being launched August 2011 in the People’s Republic of China, icotinib has been widely used in clinics, and has become an important treatment option for Chinese patients with advanced NSCLC. The present study presents the Phase I, II, and III clinical trials of icotinib and discusses current clinical applications in the People’s Republic of China and future research directions. PMID:24876785

Controversies in Alzheimer's disease drug development.

PubMed

Cummings, Jeffrey L

2008-08-01

Understanding of the pathophysiological basis of Alzheimer's disease (AD) is increasing rapidly and a variety of potential treatment modalities have emerged based on these improved mechanistic insights. The optimal way of proceeding with disease-modifying drug development remains to be clarified and controversies have emerged regarding the definition of Alzheimer's disease, the participation of mild cognitive impairment patients in clinical trials, the definition of disease modification, the potential impediments to satisfaction from patients receiving disease-modifying therapy, the importance of add-on therapy with symptomatic agents, the optimal clinical trial design to demonstrate disease modification, the best means of minimizing time spent in Phase II of drug development, the potential role of adaptive designs in clinical trials, the use of enrichment designs in clinical trials, the role of biomarkers in clinical trials, the treatment of advanced patients with disease-modifying agents, and distinctions between disease modification and disease prevention. The questions surrounding these issues must be resolved as disease-modifying therapies for AD are advanced. These controversies are framed and potential directions towards resolution described.

How clinical observation enhances recruitment and selection.

PubMed

Sutherland, Clare

2012-11-01

A survey of nurse managers in Derby Hospitals NHS Foundation Trust in 2010 found 51 practitioners working at an advanced clinical level, but there were variations in titles, pay bands, clinical skills and academic qualifications. This prompted the introduction of a local framework to support the development of the advanced nurse practitioner (ANP) role and a review of the interview process to enable managers to assess applicants' skills, competencies and knowledge. The process is now used in practice, with candidates' clinical skills now observed as part of the ANP selection process. This article describes how the new process works.

The Future of Clinical Dentistry.

ERIC Educational Resources Information Center

Slavkin, Harold C.

1998-01-01

Discussion of the future of clinical dentistry looks at a variety of influences, including historical development factors; demographic trends; the role of the Human Genome Project in the development of scientific knowledge; a paradigm shift in approaches to oral infection and systemic disease; advancing technology; and reforms resulting from these…

The NCI Alliance for Nanotechnology in Cancer: achievement and path forward.

PubMed

Ptak, Krzysztof; Farrell, Dorothy; Panaro, Nicholas J; Grodzinski, Piotr; Barker, Anna D

2010-01-01

Nanotechnology is a 'disruptive technology', which can lead to a generation of new diagnostic and therapeutic products, resulting in dramatically improved cancer outcomes. The National Cancer Institute (NCI) of National Institutes of Health explores innovative approaches to multidisciplinary research allowing for a convergence of molecular biology, oncology, physics, chemistry, and engineering and leading to the development of clinically worthy technological approaches. These initiatives include programmatic efforts to enable nanotechnology as a driver of advances in clinical oncology and cancer research, known collectively as the NCI Alliance for Nanotechnology in Cancer (ANC). Over the last 5 years, ANC has demonstrated that multidisciplinary approach catalyzes scientific developments and advances clinical translation in cancer nanotechnology. The research conducted by ANC members has improved diagnostic assays and imaging agents, leading to the development of point-of-care diagnostics, identification and validation of numerous biomarkers for novel diagnostic assays, and the development of multifunctional agents for imaging and therapy. Numerous nanotechnology-based technologies developed by ANC researchers are entering clinical trials. NCI has re-issued ANC program for next 5 years signaling that it continues to have high expectations for cancer nanotechnology's impact on clinical practice. The goals of the next phase will be to broaden access to cancer nanotechnology research through greater clinical translation and outreach to the patient and clinical communities and to support development of entirely new models of cancer care.

Next Generation Vaccine Biomarkers workshop October 30–31, 2014 – Ottawa, Canada

PubMed Central

Twine, Susan M; Fulton, Kelly M; Spika, John; Ouellette, Marc; Raven, Jennifer F; Conlan, J Wayne; Krishnan, Lakshmi; Barreto, Luis; Richards, James C

2015-01-01

Vaccine biomarkers are critical to many aspects of vaccine development and licensure, including bridging findings in pre-clinical studies to clinical studies, predicting potential adverse events, and predicting vaccine efficacy. Despite advances in our understanding of various biological pathways, and advances in systems analyses of the immune response, there remains much to learn about qualitative and quantitative aspects of the human host response to vaccination. To stimulate discussion and identify opportunities for collaborative ways to advance the field of vaccine biomarkers, A Next Generation Vaccine Biomarker workshop was held in Ottawa. The two day workshop, sponsored by the National Research Council Canada, Canadian Institutes of Health Research, Public Health Agency of Canada, Pfizer, and Medicago, brought together stakeholders from Canadian and international industry, government and academia. The workshop was grouped in themes, covering vaccine biomarker challenges in the pre-clinical and clinical spaces, veterinary vaccines, regulatory challenges, and development of biomarkers for adjuvants and cancer vaccines. The use of case studies allowed participants to identify the needs and gaps requiring innovation. The workshop concluded with a discussion on opportunities for vaccine biomarker discovery, the Canadian context, and approaches for moving forward. This article provides a synopsis of these discussions and identifies steps forward for advancing vaccine biomarker research in Canada. PMID:26383909

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.

Integrating research and clinical neuroimaging for the evaluation of traumatic brain injury recovery

NASA Astrophysics Data System (ADS)

Senseney, Justin; Ollinger, John; Graner, John; Lui, Wei; Oakes, Terry; Riedy, Gerard

2015-03-01

Advanced MRI research and other imaging modalities may serve as biomarkers for the evaluation of traumatic brain injury (TBI) recovery. However, these advanced modalities typically require off-line processing which creates images that are incompatible with radiologist viewing software sold commercially. AGFA Impax is an example of such a picture archiving and communication system(PACS) that is used by many radiology departments in the United States Military Health System. By taking advantage of Impax's use of the Digital Imaging and Communications in Medicine (DICOM) standard, we developed a system that allows for advanced medical imaging to be incorporated into clinical PACS. Radiology research can now be conducted using existing clinical imaging display platforms resources in combination with image processingtechniques that are only available outside of the clinical scanning environment. We extracted the spatial and identification elements of theDICOM standard that are necessary to allow research images to be incorporatedinto a clinical radiology system, and developed a tool that annotates research images with the proper tags. This allows for the evaluation of imaging representations of biological markers that may be useful in theevaluation of TBI and TBI recovery.

The content of the work of clinical nurse specialists described by use of daily activity diaries.

PubMed

Oddsdóttir, Elín Jakobína; Sveinsdóttir, Herdís

2011-05-01

Evaluate the usefulness of the role of clinical nurse specialists and the content of their work by mapping their activities. The clinical work of advanced practice nursing differs in different countries, and a clear picture is lacking on what exactly advanced practice nurses do. Prospective exploratory study. The setting of the study was the largest hospital in Iceland where over half of the country's active nursing workforce are employed, including the only clinical nurse specialists. Of 19 clinical nurse specialists working at the hospital, 15 participated. Data were collected over seven days with a structured activity diary that lists 65 activities, classified into six roles and three domains. In 17 instances, the 'role activities' and 'domain activities' overlap and form 17 categories of practice. The clinical nurse specialists coded their activities at 15-minutes interval and could code up to four activities simultaneously. Daily, the clinical nurse specialists evaluated their clinical nurse specialist background. The roles that occupied the greatest proportion of the clinical nurse specialists' time were education, expert practice and 'other' activities, while the smallest proportions were in counselling, research and practice development. The domain they worked in most was the institutional domain, followed by the client/family domain and the clinical outcome management domain. All of the clinical nurse specialists reported working on two activities simultaneously, 11 of them on three activities and six on four activities. They self-assessed their background as clinical nurse specialists as being very useful. The activity diary is a useful tool for assessing the content of practice. Clinical nurse specialists spend too much time on activities related to the institution. Nurse managers are advised to provide clinical nurse specialists with ample time to develop the direct practice role in the client/family domain. The development of advanced nursing practice requires that clinical nurse specialists take an active and visible part in direct patient care. © 2011 Blackwell Publishing Ltd.

Practice parameters facilitating adoption of advanced technologies for enhancing neuropsychological assessment paradigms.

PubMed

Parsons, Thomas D; McMahan, Timothy; Kane, Robert

2018-01-01

Clinical neuropsychologists have long underutilized computer technologies for neuropsychological assessment. Given the rapid advances in technology (e.g. virtual reality; tablets; iPhones) and the increased accessibility in the past decade, there is an on-going need to identify optimal specifications for advanced technologies while minimizing potential sources of error. Herein, we discuss concerns raised by a joint American Academy of Clinical Neuropsychology/National Academy of Neuropsychology position paper. Moreover, we proffer parameters for the development and use of advanced technologies in neuropsychological assessments. We aim to first describe software and hardware configurations that can impact a computerized neuropsychological assessment. This is followed by a description of best practices for developers and practicing neuropsychologists to minimize error in neuropsychological assessments using advanced technologies. We also discuss the relevance of weighing potential computer error in light of possible errors associated with traditional testing. Throughout there is an emphasis on the need for developers to provide bench test results for their software's performance on various devices and minimum specifications (documented in manuals) for the hardware (e.g. computer, monitor, input devices) in the neuropsychologist's practice. Advances in computerized assessment platforms offer both opportunities and challenges. The challenges can appear daunting but are a manageable and require informed consumers who can appreciate the issues and ask pertinent questions in evaluating their options.

Cardiac imaging: working towards fully-automated machine analysis & interpretation.

PubMed

Slomka, Piotr J; Dey, Damini; Sitek, Arkadiusz; Motwani, Manish; Berman, Daniel S; Germano, Guido

2017-03-01

Non-invasive imaging plays a critical role in managing patients with cardiovascular disease. Although subjective visual interpretation remains the clinical mainstay, quantitative analysis facilitates objective, evidence-based management, and advances in clinical research. This has driven developments in computing and software tools aimed at achieving fully automated image processing and quantitative analysis. In parallel, machine learning techniques have been used to rapidly integrate large amounts of clinical and quantitative imaging data to provide highly personalized individual patient-based conclusions. Areas covered: This review summarizes recent advances in automated quantitative imaging in cardiology and describes the latest techniques which incorporate machine learning principles. The review focuses on the cardiac imaging techniques which are in wide clinical use. It also discusses key issues and obstacles for these tools to become utilized in mainstream clinical practice. Expert commentary: Fully-automated processing and high-level computer interpretation of cardiac imaging are becoming a reality. Application of machine learning to the vast amounts of quantitative data generated per scan and integration with clinical data also facilitates a move to more patient-specific interpretation. These developments are unlikely to replace interpreting physicians but will provide them with highly accurate tools to detect disease, risk-stratify, and optimize patient-specific treatment. However, with each technological advance, we move further from human dependence and closer to fully-automated machine interpretation.

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.

Enhancing the supportive care of parents with advanced cancer: development of a self-directed educational manual.

PubMed

Turner, Jane; Clavarino, Alexandra; Yates, Patsy; Hargraves, Maryanne; Connors, Veronica; Hausmann, Sue

2008-08-01

Diagnosing and treating young patients with cancer can be stressful for health professionals; however, when the prognosis is poor and the patient has dependent children, even experienced clinicians can feel distressed and helpless. Parents with advanced cancer commonly express anxiety about the impact of the disease on their children, yet health professionals often feel unable to respond constructively because of lack of training, or concern that discussion about such difficult issues will compound parental distress. In response to this problem, an educational manual has been devised to assist oncology staff to better understand the emotional impact of parental advanced cancer, encompassing information about specific reactions of children, including strategies to help children and families cope. This paper describes the development and content of the resource which provides clinically relevant information and evidence-based recommendations to guide supportive care. The manual differs from the more traditional didactic resources in that it examines the very personal impact for professionals working with parents with advanced disease, encouraging reflection and engages the reader in clinical exercises which encourage active learning and application of knowledge into authentic clinical contexts. Although the manual is designed primarily for nurses, it is clear that much of the information is relevant for all health professionals involved in the care of parents with advanced cancer.

Using Big Data Analytics to Advance Precision Radiation Oncology.

PubMed

McNutt, Todd R; Benedict, Stanley H; Low, Daniel A; Moore, Kevin; Shpitser, Ilya; Jiang, Wei; Lakshminarayanan, Pranav; Cheng, Zhi; Han, Peijin; Hui, Xuan; Nakatsugawa, Minoru; Lee, Junghoon; Moore, Joseph A; Robertson, Scott P; Shah, Veeraj; Taylor, Russ; Quon, Harry; Wong, John; DeWeese, Theodore

2018-06-01

Big clinical data analytics as a primary component of precision medicine is discussed, identifying where these emerging tools fit in the spectrum of genomics and radiomics research. A learning health system (LHS) is conceptualized that uses clinically acquired data with machine learning to advance the initiatives of precision medicine. The LHS is comprehensive and can be used for clinical decision support, discovery, and hypothesis derivation. These developing uses can positively impact the ultimate management and therapeutic course for patients. The conceptual model for each use of clinical data, however, is different, and an overview of the implications is discussed. With advancements in technologies and culture to improve the efficiency, accuracy, and breadth of measurements of the patient condition, the concept of an LHS may be realized in precision radiation therapy. Copyright © 2018 Elsevier Inc. All rights reserved.

Alzheimer Disease

PubMed Central

Apostolova, Liana G.

2016-01-01

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

A score to estimate the likelihood of detecting advanced colorectal neoplasia at colonoscopy

PubMed Central

Kaminski, Michal F; Polkowski, Marcin; Kraszewska, Ewa; Rupinski, Maciej; Butruk, Eugeniusz; Regula, Jaroslaw

2014-01-01

Objective This study aimed to develop and validate a model to estimate the likelihood of detecting advanced colorectal neoplasia in Caucasian patients. Design We performed a cross-sectional analysis of database records for 40-year-old to 66-year-old patients who entered a national primary colonoscopy-based screening programme for colorectal cancer in 73 centres in Poland in the year 2007. We used multivariate logistic regression to investigate the associations between clinical variables and the presence of advanced neoplasia in a randomly selected test set, and confirmed the associations in a validation set. We used model coefficients to develop a risk score for detection of advanced colorectal neoplasia. Results Advanced colorectal neoplasia was detected in 2544 of the 35 918 included participants (7.1%). In the test set, a logistic-regression model showed that independent risk factors for advanced colorectal neoplasia were: age, sex, family history of colorectal cancer, cigarette smoking (p<0.001 for these four factors), and Body Mass Index (p=0.033). In the validation set, the model was well calibrated (ratio of expected to observed risk of advanced neoplasia: 1.00 (95% CI 0.95 to 1.06)) and had moderate discriminatory power (c-statistic 0.62). We developed a score that estimated the likelihood of detecting advanced neoplasia in the validation set, from 1.32% for patients scoring 0, to 19.12% for patients scoring 7–8. Conclusions Developed and internally validated score consisting of simple clinical factors successfully estimates the likelihood of detecting advanced colorectal neoplasia in asymptomatic Caucasian patients. Once externally validated, it may be useful for counselling or designing primary prevention studies. PMID:24385598

A score to estimate the likelihood of detecting advanced colorectal neoplasia at colonoscopy.

PubMed

Kaminski, Michal F; Polkowski, Marcin; Kraszewska, Ewa; Rupinski, Maciej; Butruk, Eugeniusz; Regula, Jaroslaw

2014-07-01

This study aimed to develop and validate a model to estimate the likelihood of detecting advanced colorectal neoplasia in Caucasian patients. We performed a cross-sectional analysis of database records for 40-year-old to 66-year-old patients who entered a national primary colonoscopy-based screening programme for colorectal cancer in 73 centres in Poland in the year 2007. We used multivariate logistic regression to investigate the associations between clinical variables and the presence of advanced neoplasia in a randomly selected test set, and confirmed the associations in a validation set. We used model coefficients to develop a risk score for detection of advanced colorectal neoplasia. Advanced colorectal neoplasia was detected in 2544 of the 35,918 included participants (7.1%). In the test set, a logistic-regression model showed that independent risk factors for advanced colorectal neoplasia were: age, sex, family history of colorectal cancer, cigarette smoking (p<0.001 for these four factors), and Body Mass Index (p=0.033). In the validation set, the model was well calibrated (ratio of expected to observed risk of advanced neoplasia: 1.00 (95% CI 0.95 to 1.06)) and had moderate discriminatory power (c-statistic 0.62). We developed a score that estimated the likelihood of detecting advanced neoplasia in the validation set, from 1.32% for patients scoring 0, to 19.12% for patients scoring 7-8. Developed and internally validated score consisting of simple clinical factors successfully estimates the likelihood of detecting advanced colorectal neoplasia in asymptomatic Caucasian patients. Once externally validated, it may be useful for counselling or designing primary prevention studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Proceedings of the 3rd Annual Albert Institute for Bladder Cancer Research Symposium.

PubMed

Flaig, Thomas W; Kamat, Ashish M; Hansel, Donna; Ingersoll, Molly A; Barton Grossman, H; Mendelsohn, Cathy; DeGraff, David; Liao, Joseph C; Taylor, John A

2017-07-27

The Third Annual Albert Institute Bladder Symposium was held on September 8-10th, 2016, in Denver Colorado. Participants discussed several critical topics in the field of bladder cancer: 1) Best practices for tissue analysis and use to optimize correlative studies, 2) Modeling bladder cancer to facilitate understanding and innovation, 3) Targeted therapies for bladder cancer, 4) Tumor phylogeny in bladder cancer, 5) New Innovations in bladder cancer diagnostics. Our understanding of and approach to treating urothelial carcinoma is undergoing rapid advancement. Preclinical models of bladder cancer have been leveraged to increase our basic and mechanistic understanding of the disease. With the approval of immune checkpoint inhibitors for the treatment of advanced urothelial carcinoma, the treatment approach for these patients has quickly changed. In this light, molecularly-defined subtypes of bladder cancer and appropriate pre-clinical models are now essential to the further advancement and appropriate application of these therapeutic improvements. The optimal collection and processing of clinical urothelial carcinoma tissues samples will also be critical in the development of predictive biomarkers for therapeutic selection. Technological advances in other areas including optimal imaging technologies and micro/nanotechnologies are being applied to bladder cancer, especially in the localized setting, and hold the potential for translational impact in the treatment of bladder cancer patients. Taken together, advances in several basic science and clinical areas are now converging in bladder cancer. These developments hold the promise of shaping and improving the clinical care of those with the disease.

Educating for health service reform: clinical learning, governance and capability - a case study protocol.

PubMed

Gardner, Anne; Gardner, Glenn; Coyer, Fiona; Gosby, Helen

2016-01-01

The nurse practitioner is a growing clinical role in Australia and internationally, with an expanded scope of practice including prescribing, referring and diagnosing. However, key gaps exist in nurse practitioner education regarding governance of specialty clinical learning and teaching. Specifically, there is no internationally accepted framework against which to measure the quality of clinical learning and teaching for advanced specialty practice. A case study design will be used to investigate educational governance and capability theory in nurse practitioner education. Nurse practitioner students, their clinical mentors and university academic staff, from an Australian university that offers an accredited nurse practitioner Master's degree, will be invited to participate in the study. Semi-structured interviews will be conducted with students and their respective clinical mentors and university academic staff to investigate learning objectives related to educational governance and attributes of capability learning. Limited demographic data on age, gender, specialty, education level and nature of the clinical healthcare learning site will also be collected. Episodes of nurse practitioner student specialty clinical learning will be observed and documentation from the students' healthcare learning sites will be collected. Descriptive statistics will be used to report age groups, areas of specialty and types of facilities where clinical learning and teaching is observed. Qualitative data from interviews, observations and student documents will be coded, aggregated and explored to inform a framework of educational governance, to confirm the existing capability framework and describe any additional characteristics of capability and capability learning. This research has widespread significance and will contribute to ongoing development of the Australian health workforce. Stakeholders from industry and academic bodies will be involved in shaping the framework that guides the quality and governance of clinical learning and teaching in specialty nurse practitioner practice. Through developing standards for advanced clinical learning and teaching, and furthering understanding of capability theory for advanced healthcare practitioners, this research will contribute to evidence-based models of advanced specialty postgraduate education.

Recent Advances of Cocktail Chemotherapy by Combination Drug Delivery Systems

PubMed Central

Hu, Quanyin; Sun, Wujin; Wang, Chao; Gu, Zhen

2016-01-01

Combination chemotherapy is widely exploited for enhanced cancer treatment in clinic. However, the traditional cocktail administration of combination regimens often suffers from varying pharmacokinetics among different drugs. The emergence of nanotechnology offers an unparalleled opportunity for developing advanced combination drug delivery strategies with the ability to encapsulate various drugs simultaneously and unify the pharmacokinetics of each drug. This review surveys the most recent advances in combination delivery of multiple small molecule chemotherapeutics using nanocarriers. The mechanisms underlying combination chemotherapy, including the synergistic, additive and potentiation effects, are also discussed with typical examples. We further highlight the sequential and site-specific co-delivery strategies, which provide new guidelines for development of programmable combination drug delivery systems. Clinical outlook and challenges are also discussed in the end. PMID:26546751

Challenges and perspective of drug repurposing strategies in early phase clinical trials.

PubMed

Kato, Shumei; Moulder, Stacy L; Ueno, Naoto T; Wheler, Jennifer J; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

2015-01-01

Despite significant investments in the development of new agents only 5% of cancer drugs entering Phase I clinical trials are ultimately approved for routine clinical cancer care. Drug repurposing strategies using novel combinations of previously tested anticancer agents could reduce the cost and improve treatment outcomes. At MD Anderson Cancer Center, early phase clinical trials with drug repurposing strategies demonstrated promising outcomes in patients with both rare and common treatment refractory advanced cancers. Despite clinical efficacy advancing drug repurposing strategies in the clinical trial trajectory beyond early phase studies has been challenging mainly due to lack of funding and interest from the pharmaceutical industry. In this review, we delineate our experience and challenges with drug repurposing strategies.

[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.

Clinical Assessment in Mathematics: Learning the Craft.

ERIC Educational Resources Information Center

Hunting, Robert P.; Doig, Brian A.

1997-01-01

Discusses a professional development program called Clinical Approaches to Mathematics Assessment. Argues for the advanced training of mathematics teachers who understand knowledge construction processes of students; can use clinical tools for evaluating a student's unique mathematical "fingerprint"; and can create or adapt problems, tasks, or…

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.

First-line therapy for advanced non-small cell lung cancer with activating EGFR mutation: is combined EGFR-TKIs and chemotherapy a better choice?

PubMed

Wang, Shuyun; Gao, Aiqin; Liu, Jie; Sun, Yuping

2018-03-01

As the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutation, EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved the median progression-free survival (PFS) up to 18.9 months. However, almost all patients eventually develop acquired resistance to EGFR-TKIs, which limits the first-line PFS. To overcome the resistance and improve overall survival, researchers have tried to identify the resistance mechanisms and develop new treatment strategies, among which a combination of EGFR-TKIs and cytotoxic chemotherapy is one of the hotspots. The data from preclinical and clinical studies on combined EGFR-TKIs and chemotherapy have shown very interesting results. Here, we reviewed the available preclinical and clinical studies on first-line EGFR-TKIs-chemotherapy combination in patients with advanced NSCLC harboring activating EGFR mutation, aiming to provide evidences for more potential choices and shed light on clinical treatment.

Rational design and optimization of downstream processes of virus particles for biopharmaceutical applications: current advances.

PubMed

Vicente, Tiago; Mota, José P B; Peixoto, Cristina; Alves, Paula M; Carrondo, Manuel J T

2011-01-01

The advent of advanced therapies in the pharmaceutical industry has moved the spotlight into virus-like particles and viral vectors produced in cell culture holding great promise in a myriad of clinical targets, including cancer prophylaxis and treatment. Even though a couple of cases have reached the clinic, these products have yet to overcome a number of biological and technological challenges before broad utilization. Concerning the manufacturing processes, there is significant research focusing on the optimization of current cell culture systems and, more recently, on developing scalable downstream processes to generate material for pre-clinical and clinical trials. We review the current options for downstream processing of these complex biopharmaceuticals and underline current advances on knowledge-based toolboxes proposed for rational optimization of their processing. Rational tools developed to increase the yet scarce knowledge on the purification processes of complex biologicals are discussed as alternative to empirical, "black-boxed" based strategies classically used for process development. Innovative methodologies based on surface plasmon resonance, dynamic light scattering, scale-down high-throughput screening and mathematical modeling for supporting ion-exchange chromatography show great potential for a more efficient and cost-effective process design, optimization and equipment prototyping. Copyright © 2011 Elsevier Inc. All rights reserved.

Current and proposed molecular diagnostics in a genitourinary service line laboratory at a tertiary clinical institution.

PubMed

Udager, Aaron M; Alva, Ajjai; Mehra, Rohit

2014-01-01

The idea that detailed knowledge of molecular oncogenesis will drive diagnostic, prognostic, and therapeutic clinical decision making in an increasingly multidisciplinary practice of oncologic care has been anticipated for many years. With the recent rapid advancement in our understanding of the molecular underpinnings of genitourinary malignancies, this concept is now starting to take shape in the fields of prostate, kidney, bladder, testicular, and penile cancer. Such breakthroughs necessitate the development of robust clinical-grade assays that can be quickly made available for patients to facilitate diagnosis in challenging cases, risk-stratify patients for subsequent clinical management, select the appropriate targeted therapy from among increasingly diverse and numerous options, and enroll patients in advanced clinical trials. This rapid translation of basic and clinical cancer research requires a streamlined, multidisciplinary approach to clinical assay development, termed here the molecular diagnostics service line laboratory. In this review, we summarize the current state and explore the future of molecular diagnostics in genitourinary oncology to conceptualize a genitourinary service line laboratory at a tertiary clinical institution.

Chapter 2 evolution of burn management in the u.s. Military: impact on nursing.

PubMed

Schmidt, Patricia; Mann-Salinas, Elizabeth A

2014-01-01

As the only burn center in the Department of Defense, the U.S. Army Institute of Surgical Research is the primary location for care of service members with burn injuries. The combat operations in Iraq and Afghanistan during the past decade have caused an increase in burn patients. As a result of this increased need, advancements in care were developed. The speed and precision of transporting patients from the battlefield to the burn center has improved over previous conflicts. Technological advancements to support treating complications of burn wound healing were leveraged and are now integrated into daily practice. Clinical decision support systems were developed and deployed at the burn center as well as to combat support hospitals in combat zones. Technology advancements in rehabilitation have allowed more service members to return to active duty or live productive civilian lives. All of these advancements were developed in a patient-centered, interdisciplinary environment where the nurses are integrated throughout the research process and clinical practice with the end goal of healing combat burns in mind.

Evaluating Clinical Teaching in Medicine.

ERIC Educational Resources Information Center

Irby, David; Rakestraw, Philip

1981-01-01

Medical students have been rating clinical teaching in an obstetrics and gynecology clerkship at the University of Washington using an assessment form designed to reflect six factors of clinical teaching effectiveness. High interrater reliability and the utility of the data for faculty development and advancement are discussed. (Author/JMD)

Controversies in Alzheimer’s disease drug development

PubMed Central

Cummings, Jeffrey L.

2010-01-01

Understanding of the pathophysiological basis of Alzheimer’s disease (AD) is increasing rapidly and a variety of potential treatment modalities have emerged based on these improved mechanistic insights. The optimal way of proceeding with disease-modifying drug development remains to be clarified and controversies have emerged regarding the definition of Alzheimer’s disease, the participation of mild cognitive impairment patients in clinical trials, the definition of disease modification, the potential impediments to satisfaction from patients receiving disease-modifying therapy, the importance of add-on therapy with symptomatic agents, the optimal clinical trial design to demonstrate disease modification, the best means of minimizing time spent in Phase II of drug development, the potential role of adaptive designs in clinical trials, the use of enrichment designs in clinical trials, the role of biomarkers in clinical trials, the treatment of advanced patients with disease-modifying agents, and distinctions between disease modification and disease prevention. The questions surrounding these issues must be resolved as disease-modifying therapies for AD are advanced. These controversies are framed and potential directions towards resolution described. PMID:18925488

Revisioning a clinical nurse specialist curriculum in 3 specialty tracks.

PubMed

Arslanian-Engoren, Cynthia; Sullivan, Barbara-Jean; Struble, Laura

2011-01-01

The objective of the present study was to revise 3 clinical nurse specialist (CNS) educational tracks with current National Association of Clinical Nurse Specialist core competencies and educational expectations. National curricula recommendations include core competencies by the 3 spheres of influence. Advanced practice registered nurses consensus model educational requirements include a minimum of 500 faculty-supervised clinical hours; separate graduate courses in pharmacology, pathophysiology, and advanced physical assessment; and content in differential diagnosis disease management, decision making, and role preparation. This educational initiative was designed to (1) align with core competencies and advanced practice registered nurse consensus model recommendations, (2) create an innovative learning environment, (3) meet the needs of diverse student populations, (4) align with emerging doctor of nursing practice programs, (5) create a high-efficiency and high-quality environment to manage human and fiscal resources, and (6) reduce duplication of efforts. Courses were revised that did not meet current CNS educational preparation expectations. A total of 11 didactic and clinical sequences courses were developed for the 3 tracks to (1) ensure minimum numbers of clinical hours; (2) expand content on health promotion and risk reduction, advanced practice nurse role, and the healthcare delivery system; (3) consolidate clinical courses; and (4) resequence foundational content before beginning clinical courses. Revisioning a CNS curriculum in 3 specialty tracks is challenging but doable using innovative and creative approaches. The innovative process used to revise our CNS curriculum will assist nurse educators faced with similar program delivery challenges to meet future directions for educating CNS students in advanced nursing practice. Copyright © 2011 Lippincott Williams & Wilkins.

Delineating advanced practice nursing in New Zealand: a national survey.

PubMed

Carryer, J; Wilkinson, J; Towers, A; Gardner, G

2018-03-01

A variety of advanced practice nursing roles and titles have proliferated in response to the changing demands of a population characterized by increasing age and chronic illness. Whilst similarly identified as advanced practice roles, they do not share a common practice profile, educational requirements or legislative direction. The lack of clarity limits comparative research that can inform policy and health service planning. To identify advanced practice roles within nursing titles employed in New Zealand and practice differences between advanced practice and other roles. Replicating recent Australian research, 3255 registered nurses/nurse practitioners in New Zealand completed the amended Advanced Practice Delineation survey tool. The mean domain scores of the predominant advanced practice position were compared with those of other positions. Differences between groups were explored using one-way ANOVA and post hoc between group comparisons. Four nursing position bands were identified: nurse practitioner, clinical nurse specialist, domain-specific and registered nurse. Significant differences between the bands were found on many domain scores. The nurse practitioner and clinical nurse specialist bands had the most similar practice profiles, nurse practitioners being more involved in direct care and professional leadership. Similar to the position of clinical nurse consultant in Australia, those practicing as clinical nurse specialists were deemed to reflect the threshold for advanced practice nursing. The results identified different practice patterns for the identified bands and distinguish the advanced practice nursing roles. By replicating the Australian study of Gardener et al. (2016), this NZ paper extends the international data available to support more evidence-based nursing workforce planning and policy development. © 2017 International Council of Nurses.

The Influence of Big (Clinical) Data and Genomics on Precision Medicine and Drug Development.

PubMed

Denny, Joshua C; Van Driest, Sara L; Wei, Wei-Qi; Roden, Dan M

2018-03-01

Drug development continues to be costly and slow, with medications failing due to lack of efficacy or presence of toxicity. The promise of pharmacogenomic discovery includes tailoring therapeutics based on an individual's genetic makeup, rational drug development, and repurposing medications. Rapid growth of large research cohorts, linked to electronic health record (EHR) data, fuels discovery of new genetic variants predicting drug action, supports Mendelian randomization experiments to show drug efficacy, and suggests new indications for existing medications. New biomedical informatics and machine-learning approaches advance the ability to interpret clinical information, enabling identification of complex phenotypes and subpopulations of patients. We review the recent history of use of "big data" from EHR-based cohorts and biobanks supporting these activities. Future studies using EHR data, other information sources, and new methods will promote a foundation for discovery to more rapidly advance precision medicine. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Combination therapy for advanced or metastatic non-small cell lung cancer will be tested in new clinical trial | Center for Cancer Research

Cancer.gov

Non-small cell lung cancer (NSCLC) develops when abnormal lung cells begin to grow out of control. These cells can form into a tumor and spread to other areas of the body. David Schrump, M.D., of the Thoracic and Gastrointestinal Oncology Branch is leading a clinical trial of a new combination treatment for patients with advanced or metastatic NSCLC that cannot be treated

Phacilitate Barcelona active immunotherapeutics forum. 11-13 May 2011, Barcelona, Spain.

PubMed

Shore, Neal D

2011-08-01

The era of active immunotherapy has now been successfully ushered into the clinical realm of advanced prostate cancer. The successful clinical trial development and US FDA approval of sipuleucel-T (Provenge®) has revamped the therapeutic paradigm for advanced prostate cancer. Nonetheless, physician and patient education as well as regulatory pathways and manufacturing efficiencies are still required in order to optimize patient care. These topics were covered at the Phacilitate Barcelona Active Immunotherapeutics Forum.

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.

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.

Urological cancer care pathways: development and use in the context of systematic reviews and clinical practice guidelines.

PubMed

Maclennan, Sara Jane; Maclennan, Steven J; Imamura, Mari; Omar, Muhammad Imran; Vale, Luke; Lam, Thomas; Royle, Pamela; Royle, Justine; Swami, Satchi; Pickard, Rob; McClinton, Sam; Griffiths, T R Leyshon; Dahm, Philipp; N'dow, James

2011-06-01

Making healthcare treatment decisions is a complex process involving a broad stakeholder base including patients, their families, health professionals, clinical practice guideline developers and funders of healthcare. This paper presents a review of a methodology for the development of urological cancer care pathways (UCAN care pathways), which reflects an appreciation of this broad stakeholder base. The methods section includes an overview of the steps in the development of the UCAN care pathways and engagement with clinical content experts and patient groups. The development process is outlined, the uses of the urological cancer care pathways discussed and the implications for clinical practice highlighted. The full set of UCAN care pathways is published in this paper. These include care pathways on localised prostate cancer, locally advanced prostate cancer, metastatic prostate cancer, hormone-resistant prostate cancer, localised renal cell cancer, advanced renal cell cancer, testicular cancer, penile cancer, muscle invasive and metastatic bladder cancer and non-muscle invasive bladder cancer. The process provides a useful framework for improving urological cancer care through evidence synthesis, research prioritisation, stakeholder involvement and international collaboration. Although the focus of this work is urological cancers, the methodology can be applied to all aspects of urology and is transferable to other clinical specialties.

The evolving landscape of therapeutic drug development for hepatocellular carcinoma.

PubMed

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

2013-11-01

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

High-Resolution Methods for Diagnosing Cartilage Damage In Vivo

PubMed Central

Novakofski, Kira D.; Pownder, Sarah L.; Koff, Matthew F.; Williams, Rebecca M.; Potter, Hollis G.; Fortier, Lisa A.

2016-01-01

Advances in current clinical modalities, including magnetic resonance imaging and computed tomography, allow for earlier diagnoses of cartilage damage that could mitigate progression to osteoarthritis. However, current imaging modalities do not detect submicrometer damage. Developments in in vivo or arthroscopic techniques, including optical coherence tomography, ultrasonography, bioelectricity including streaming potential measurement, noninvasive electroarthrography, and multiphoton microscopy can detect damage at an earlier time point, but they are limited by a lack of penetration and the ability to assess an entire joint. This article reviews current advancements in clinical and developing modalities that can aid in the early diagnosis of cartilage injury and facilitate studies of interventional therapeutics. PMID:26958316

Advances in the development of new tuberculosis drugs and treatment regimens.

PubMed

Zumla, Alimuddin; Nahid, Payam; Cole, Stewart T

2013-05-01

Despite the introduction 40 years ago of the inexpensive and effective four-drug (isoniazid, rifampicin, pyrazinamide and ethambutol) treatment regimen, tuberculosis (TB) continues to cause considerable morbidity and mortality worldwide. For the first time since the 1960s, new and novel drugs and regimens for all forms of TB are emerging. Such regimens are likely to utilize both repurposed drugs and new chemical entities, and several of these regimens are now progressing through clinical trials. This article covers current concepts and recent advances in TB drug discovery and development, including an update of ongoing TB treatment trials, newer clinical trial designs, TB biomarkers and adjunct host-directed therapies.

Cardiac imaging: working towards fully-automated machine analysis & interpretation

PubMed Central

Slomka, Piotr J; Dey, Damini; Sitek, Arkadiusz; Motwani, Manish; Berman, Daniel S; Germano, Guido

2017-01-01

Introduction Non-invasive imaging plays a critical role in managing patients with cardiovascular disease. Although subjective visual interpretation remains the clinical mainstay, quantitative analysis facilitates objective, evidence-based management, and advances in clinical research. This has driven developments in computing and software tools aimed at achieving fully automated image processing and quantitative analysis. In parallel, machine learning techniques have been used to rapidly integrate large amounts of clinical and quantitative imaging data to provide highly personalized individual patient-based conclusions. Areas covered This review summarizes recent advances in automated quantitative imaging in cardiology and describes the latest techniques which incorporate machine learning principles. The review focuses on the cardiac imaging techniques which are in wide clinical use. It also discusses key issues and obstacles for these tools to become utilized in mainstream clinical practice. Expert commentary Fully-automated processing and high-level computer interpretation of cardiac imaging are becoming a reality. Application of machine learning to the vast amounts of quantitative data generated per scan and integration with clinical data also facilitates a move to more patient-specific interpretation. These developments are unlikely to replace interpreting physicians but will provide them with highly accurate tools to detect disease, risk-stratify, and optimize patient-specific treatment. However, with each technological advance, we move further from human dependence and closer to fully-automated machine interpretation. PMID:28277804

Development of replication-competent viral vectors for HIV vaccine delivery

PubMed Central

Parks, Christopher L.; Picker, Louis J.; King, C. Richter

2014-01-01

Purpose of review Briefly describe some of the replication-competent (RC) vectors being investigated for development of candidate HIV vaccines focusing primarily on technologies that have advanced to testing in macaques or have entered clinical trials. Recent findings RC viral vectors have advanced to the stage were decisions can be made regarding future development of HIV vaccines. The viruses being used as RC vector platforms vary considerably, and their unique attributes make it possible to test multiple vaccine design concepts and also mimic various aspects of an HIV infection. RC viral vectors encoding SIV or HIV proteins can be used to safely immunize macaques, and in some cases, there is evidence of significant vaccine efficacy in challenge protection studies. Several live HIV vaccine vectors are in clinical trials to evaluate immunogenicity, safety, the effect of mucosal delivery, and potential effects of pre-existing immunity. Summary A variety of DNA and RNA viruses are being used to develop RC viral vectors for HIV vaccine delivery. Multiple viral vector platforms have proven to be safe and immunogenic with evidence of efficacy in macaques. Some of the more advanced HIV vaccine prototypes based on vesicular stomatitis virus, vaccinia virus, measles virus, and Sendai virus are in clinical trials. PMID:23925000

Next-Generation Proteomics and Its Application to Clinical Breast Cancer Research.

PubMed

Mardamshina, Mariya; Geiger, Tamar

2017-10-01

Proteomics technology aims to map the protein landscapes of biological samples, and it can be applied to a variety of samples, including cells, tissues, and body fluids. Because the proteins are the main functional molecules in the cells, their levels reflect much more accurately the cellular phenotype and the regulatory processes within them than gene levels, mutations, and even mRNA levels. With the advancement in the technology, it is possible now to obtain comprehensive views of the biological systems and to study large patient cohorts in a streamlined manner. In this review we discuss the technological advancements in mass spectrometry-based proteomics, which allow analysis of breast cancer tissue samples, leading to the first large-scale breast cancer proteomics studies. Furthermore, we discuss the technological developments in blood-based biomarker discovery, which provide the basis for future development of assays for routine clinical use. Although these are only the first steps in implementation of proteomics into the clinic, extensive collaborative work between these worlds will undoubtedly lead to major discoveries and advances in clinical practice. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Systems to identify potentially inappropriate prescribing in people with advanced dementia: a systematic review.

PubMed

Disalvo, Domenica; Luckett, Tim; Agar, Meera; Bennett, Alexandra; Davidson, Patricia Mary

2016-05-31

Systems for identifying potentially inappropriate medications in older adults are not immediately transferrable to advanced dementia, where the management goal is palliation. The aim of the systematic review was to identify and synthesise published systems and make recommendations for identifying potentially inappropriate prescribing in advanced dementia. Studies were included if published in a peer-reviewed English language journal and concerned with identifying the appropriateness or otherwise of medications in advanced dementia or dementia and palliative care. The quality of each study was rated using the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist. Synthesis was narrative due to heterogeneity among designs and measures. Medline (OVID), CINAHL, the Cochrane Database of Systematic Reviews (2005 - August 2014) and AMED were searched in October 2014. Reference lists of relevant reviews and included articles were searched manually. Eight studies were included, all of which were scored a high quality using the STROBE checklist. Five studies used the same system developed by the Palliative Excellence in Alzheimer Care Efforts (PEACE) Program. One study used number of medications as an index, and two studies surveyed health professionals' opinions on appropriateness of specific medications in different clinical scenarios. Future research is needed to develop and validate systems with clinical utility for improving safety and quality of prescribing in advanced dementia. Systems should account for individual clinical context and distinguish between deprescribing and initiation of medications.

Development and application of neuropsychology in Hong Kong: implications of its value and future advancement.

PubMed

Chan, Agnes S; Sze, Sophia L; Cheung, Mei-Chun; Han, Yvonne M Y

2016-11-01

To review the development, application, and value of neuropsychology, and the standard education and training pathway for neuropsychologists or clinical neuropsychologists in Hong Kong. The information provided here was gathered via a literature review of the status of neuropsychology and the validity of commonly adopted neuropsychological tests in Hong Kong. Additional details were acquired via the internet about local tertiary education curricula and the related requirements, the availability of professional associations for licensure or board certification, and relevant statistics/surveys conducted by the government. Some information about the clinical practice of neuropsychology was collected through personal communication with local clinical psychologists. The development of neuropsychology in Hong Kong over the past 20 years is rapid and productive, given the increasing application of advanced neuroimaging techniques, neuropsychological tests, and opportunities for exchanging up-to-date neuropsychological knowledge and professional training through international conferences, workshops, and seminars. Given that neuropsychology services are often provided by clinical psychologists who are master's degree graduates in clinical psychology, the relatively limited training in neuropsychological knowledge and skills and the lack of division for membership or mandatory registration as a neuropsychologist/clinical neuropsychologist may have an impact on the quality of clinical neuropsychological services and the development of this specialty. These findings signify a need for further improvement or refinement of educational and training pathways for neuropsychologist or clinical neuropsychologist along with the recognition of its value in clinical practice through registration of different disciplines of psychology in Hong Kong.

Recent Developments in Dystonia

PubMed Central

Jinnah, H. A.; Teller, Jan K.; Galpern, Wendy R.

2015-01-01

Purpose of review The dystonias are a family of related disorders with many different clinical manifestations and causes. This review summarizes recent developments regarding these disorders, focusing mainly on advances with direct clinical relevance from the past two years. Recent findings The dystonias are generally defined by their clinical characteristics, rather than by their underlying genetic or neuropathological defects. The many varied clinical manifestations and causes contribute to the fact that they are one of the most poorly recognized of all movement disorders. A series of recent publications has addressed these issues offering a revised definition and more logical means for classifying the many subtypes. Our understanding of the genetic and neurobiological mechanisms responsible for different types of dystonias also has grown rapidly, creating new opportunities and challenges for diagnosis and identifying increasing numbers of rare subtypes for which specific treatments are available. Summary Recent advances in describing the clinical phenotypes and determining associated genotypes have pointed to the need for new strategies for diagnosis, classification and treatment of the dystonias. PMID:26110799

Reflective Journaling for Critical Thinking Development in Advanced Practice Registered Nurse Students.

PubMed

Raterink, Ginger

2016-02-01

Critical thinking, clinical decision making, and critical reflection have been identified as skills required of nurses in every clinical situation. The Educating Nurses: A Call for Radical Transformation report suggested that critical reflection is a key to improving the educational process. Reflective journaling is a tool that helps develop such skills. This article presents the tool of reflective journaling and the use of this process by educators working with students. It describes the use of reflective journaling in graduate nursing education, as well as a scoring process to evaluate the reflection and provide feedback. Students and faculty found the journaling to be helpful for reflection of a clinical situation focused on critical thinking skill development. The rubric scoring tool provided faculty with a method for feedback. Reflective journaling is a tool that faculty and students can use to develop critical thinking skills for the role of the advanced practice RN. A rubric scoring system offers a consistent format for feedback. Copyright 2016, SLACK Incorporated.

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

Development of Personalized Cancer Therapy for Men with Advanced Prostate Cancer

DTIC Science & Technology

2016-10-01

05/31/2017 The overall goal of this project is to bring together expertise at the University of Michigan including clinical oncology , cancer genetics...variants into clinical oncology setting; 5) Assess and evaluate costs associated with clinical sequencing. W81XWH-12-1-0080 Title: Time Commitment...Michigan including clinical oncology , cancer genetics, genomic science/bioinformatics, clinical pathology, social and behavioral sciences, and

[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.

Engineered Heart Repair.

PubMed

Fujita, B; Zimmermann, W-H

2017-08-01

There is a pressing need for the development of advanced heart failure therapeutics. Current state-of-the-art is protection from neurohumoral overstimulation, which fails to address the underlying cause of heart failure, namely loss of cardiomyocytes. Implantation of stem cell-derived cardiomyocytes via tissue-engineered myocardium is being advanced to realize the remuscularization of the failing heart. Here, we discuss pharmacological challenges pertaining to the clinical translation of tissue-engineered heart repair with a focus on engineered heart muscle (EHM). © 2017 American Society for Clinical Pharmacology and Therapeutics.

Access to augmentative and alternative communication: new technologies and clinical decision-making.

PubMed

Fager, Susan; Bardach, Lisa; Russell, Susanne; Higginbotham, Jeff

2012-01-01

Children with severe physical impairments require a variety of access options to augmentative and alternative communication (AAC) and computer technology. Access technologies have continued to develop, allowing children with severe motor control impairments greater independence and access to communication. This article will highlight new advances in access technology, including eye and head tracking, scanning, and access to mainstream technology, as well as discuss future advances. Considerations for clinical decision-making and implementation of these technologies will be presented along with case illustrations.

Combination therapy for advanced or metastatic non-small cell lung cancer will be tested in new clinical trial | Center for Cancer Research

Cancer.gov

Non-small cell lung cancer (NSCLC) develops when abnormal lung cells begin to grow out of control. These cells can form into a tumor and spread to other areas of the body. David Schrump, M.D., of the Thoracic and Gastrointestinal Oncology Branch is leading a clinical trial of a new combination treatment for patients with advanced or metastatic NSCLC that cannot be treated surgically. Read more... 

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.

Anti-MRSA beta-lactams in development.

PubMed

Page, Malcolm G P

2006-10-01

Ceftobiprole medocaril, the most advanced of the anti-MRSA (methicillin-resistant Staphylococcus aureus) beta-lactams in clinical development, has recently completed its first Phase III clinical trial, and has demonstrated non-inferiority to vancomycin. Phase II clinical trials have been initiated with PPI0903, which is, like ceftobiprole medocaril, an injectable pro-drug of a broad-spectrum cephalosporin with anti-MRSA activity, and with RO4908643, a carbapenem with more modest activity against MRSA.

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.

Quantifying Disease Progression in Amyotrophic Lateral Sclerosis

PubMed Central

Simon, Neil G; Turner, Martin R; Vucic, Steve; Al-Chalabi, Ammar; Shefner, Jeremy; Lomen-Hoerth, Catherine; Kiernan, Matthew C

2014-01-01

Amyotrophic lateral sclerosis (ALS) exhibits characteristic variability of onset and rate of disease progression, with inherent clinical heterogeneity making disease quantitation difficult. Recent advances in understanding pathogenic mechanisms linked to the development of ALS impose an increasing need to develop strategies to predict and more objectively measure disease progression. This review explores phenotypic and genetic determinants of disease progression in ALS, and examines established and evolving biomarkers that may contribute to robust measurement in longitudinal clinical studies. With targeted neuroprotective strategies on the horizon, developing efficiencies in clinical trial design may facilitate timely entry of novel treatments into the clinic. PMID:25223628

Coping Well with Advanced Cancer: A Serial Qualitative Interview Study with Patients and Family Carers

PubMed Central

Roberts, Diane; Appleton, Lynda; Calman, Lynn; Large, Paul; Lloyd-Williams, Mari; Grande, Gunn

2017-01-01

Objectives To understand successful strategies used by people to cope well when living with advanced cancer; to explore how professionals can support effective coping strategies; to understand how to support development of effective coping strategies for patients and family carers. Design Qualitative serial (4–12 week intervals) interview study with people with advanced cancer and their informal carers followed by focus groups. The iterative design had a novel focus on positive coping strategies. Interview analysis focused on patients and carers as individuals and pairs, exploring multiple dimensions of their coping experiences. Focus group analysis explored strategies for intervention development. Participants 26 people with advanced (stage 3–4) breast, prostate, lung or colorectal cancer, or in receipt of palliative care, and 24 paired nominated informal/family carers. Setting Participants recruited through outpatient clinics at two tertiary cancer centres in Merseyside and Manchester, UK, between June 2012 and July 2013. Results 45 patient and 41 carer interviews were conducted plus 4 focus groups (16 participants). People with advanced cancer and their informal/family carers develop coping strategies which enable effective management of psychological wellbeing. People draw from pre-diagnosis coping strategies, but these develop through responding to the experience of living with advanced cancer. Strategies include being realistic, indulgence, support, and learning from others, which enabled participants to regain a sense of wellbeing after emotional challenge. Learning from peers emerged as particularly important in promoting psychological wellbeing through the development of effective ‘everyday’, non-clinical coping strategies. Conclusions Our findings challenge current models of providing psychological support for those with advanced cancer which focus on professional intervention. It is important to recognise, enable and support peoples’ own resources and coping strategies. Peer support may have potential, and could be a patient-centred, cost effective way of managing the needs of a growing population of those living with advanced cancer. PMID:28107352

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

PubMed

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

2017-08-01

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

Imaging: Guiding the Clinical Translation of Cardiac Stem Cell Therapy

PubMed Central

Nguyen, Patricia K.; Lan, Feng; Wang, Yongming; Wu, Joseph C.

2011-01-01

Stem cells have been touted as the holy grail of medical therapy with promises to regenerate cardiac tissue, but it appears the jury is still out on this novel therapy. Using advanced imaging technology, scientists have discovered that these cells do not survive nor engraft long-term. In addition, only marginal benefit has been observed in large animal studies and human trials. However, all is not lost. Further application of advanced imaging technology will help scientists unravel the mysteries of stem cell therapy and address the clinical hurdles facing its routine implementation. In this review, we will discuss how advanced imaging technology will help investigators better define the optimal delivery method, improve survival and engraftment, and evaluate efficacy and safety. Insights gained from this review may direct the development of future preclinical investigations and clinical trials. PMID:21960727

Concise Review: Process Development Considerations for Cell Therapy

PubMed Central

Brieva, Thomas; Raviv, Lior; Rowley, Jon; Niss, Knut; Brandwein, Harvey; Oh, Steve; Karnieli, Ohad

2015-01-01

The development of robust and well-characterized methods of production of cell therapies has become increasingly important as therapies advance through clinical trials toward approval. A successful cell therapy will be a consistent, safe, and effective cell product, regardless of the cell type or application. Process development strategies can be developed to gain efficiency while maintaining or improving safety and quality profiles. This review presents an introduction to the process development challenges of cell therapies and describes some of the tools available to address production issues. This article will provide a summary of what should be considered to efficiently advance a cellular therapy from the research stage through clinical trials and finally toward commercialization. The identification of the basic questions that affect process development is summarized in the target product profile, and considerations for process optimization are discussed. The goal is to identify potential manufacturing concerns early in the process so they may be addressed effectively and thus increase the probability that a therapy will be successful. Significance The present study contributes to the field of cell therapy by providing a resource for those transitioning a potential therapy from the research stage to clinical and commercial applications. It provides the necessary steps that, when followed, can result in successful therapies from both a clinical and commercial perspective. PMID:26315572

[Hand transplantation and implantation of nerve chips. New developments within hand surgery].

PubMed

Dahlin, L; Fridén, J; Hagberg, L; Lundborg, G

1999-10-06

Injuries and diseases of the hand naturally have an enormous impact on hand function and on quality of life, both occupational and social. The majority of hand-injury patients are under 30 years of age. Hand surgery, an established specialty in Sweden since 1969, is of great importance in terms of clinical developments, education and research. In the coming decade, scientific and clinical advances are to be expected in several fields such as nerve injuries including brachial plexus lesion, microsurgery, flexor tendon injuries and tendon transfer. Bioimplant research and new advances at the biotechnological interface will yield new options in nerve reconstruction, microchip implants in the nervous system, and the restoration of muscle-tendon function following injury. Artificial limbs with advanced motor and sensory functions will be important future aids in the rehabilitation of amputees. Transplantation of human hands is another promising reconstructive procedure which may open up new perspectives in the coming millennium.

[Hand transplantation and implantation of nerve chips. New developments within hand surgery].

PubMed

Dahlin, L; Fridén, J; Hagberg, L; Lundborg, G

2000-03-20

Injuries and diseases of the hand naturally have an enormous impact on hand function and on quality of life, both occupational and social. The majority of hand-injury patients are under 30 years of age. Hand surgery, an established specialty in Sweden since 1969, is of great importance in terms of clinical developments, education and research. In the coming decade, scientific and clinical advances are to be expected in several fields such as nerve injuries including brachial plexus lesion, microsurgery, flexor tendon injuries and tendon transfer. Bioimplant research and new advances at the biotechnological interface will yield new options in nerve reconstruction, microchip implants in the nervous system, and the restoration of muscle-tendon function following injury. Artificial limbs with advanced motor and sensory functions will be important future aids in the rehabilitation of amputees. Transplantation of human hands is another promising reconstructive procedure which may open iup new perspectives in the coming millennium.

Three-dimensional bio-printing: A new frontier in oncology research

PubMed Central

Charbe, Nitin; McCarron, Paul A; Tambuwala, Murtaza M

2017-01-01

Current research in oncology deploys methods that rely principally on two-dimensional (2D) mono-cell cultures and animal models. Although these methodologies have led to significant advancement in the development of novel experimental therapeutic agents with promising anticancer activity in the laboratory, clinicians still struggle to manage cancer in the clinical setting. The disappointing translational success is attributable mainly to poor representation and recreation of the cancer microenvironment present in human neoplasia. Three-dimensional (3D) bio-printed models could help to simulate this micro-environment, with recent bio-printing of live human cells demonstrating that effective in vitro replication is achievable. This literature review outlines up-to-date advancements and developments in the use of 3D bio-printed models currently being used in oncology research. These innovative advancements in 3D bio-printing open up a new frontier for oncology research and could herald an era of progressive clinical cancer therapeutics. PMID:28246583

Bluetooth Roaming for Sensor Network System in Clinical Environment.

PubMed

Kuroda, Tomohiro; Noma, Haruo; Takase, Kazuhiko; Sasaki, Shigeto; Takemura, Tadamasa

2015-01-01

A sensor network is key infrastructure for advancing a hospital information system (HIS). The authors proposed a method to provide roaming functionality for Bluetooth to realize a Bluetooth-based sensor network, which is suitable to connect clinical devices. The proposed method makes the average response time of a Bluetooth connection less than one second by making the master device repeat the inquiry process endlessly and modifies parameters of the inquiry process. The authors applied the developed sensor network for daily clinical activities in an university hospital, and confirmed the stabilitya and effectiveness of the sensor network. As Bluetooth becomes a quite common wireless interface for medical devices, the proposed protocol that realizes Bluetooth-based sensor network enables HIS to equip various clinical devices and, consequently, lets information and communication technologies advance clinical services.

Successful applications of computer aided drug discovery: moving drugs from concept to the clinic.

PubMed

Talele, Tanaji T; Khedkar, Santosh A; Rigby, Alan C

2010-01-01

Drug discovery and development is an interdisciplinary, expensive and time-consuming process. Scientific advancements during the past two decades have changed the way pharmaceutical research generate novel bioactive molecules. Advances in computational techniques and in parallel hardware support have enabled in silico methods, and in particular structure-based drug design method, to speed up new target selection through the identification of hits to the optimization of lead compounds in the drug discovery process. This review is focused on the clinical status of experimental drugs that were discovered and/or optimized using computer-aided drug design. We have provided a historical account detailing the development of 12 small molecules (Captopril, Dorzolamide, Saquinavir, Zanamivir, Oseltamivir, Aliskiren, Boceprevir, Nolatrexed, TMI-005, LY-517717, Rupintrivir and NVP-AUY922) that are in clinical trial or have become approved for therapeutic use.

MicroPET imaging and transgenic models: a blueprint for Alzheimer's disease clinical research.

PubMed

Zimmer, Eduardo R; Parent, Maxime J; Cuello, A Claudio; Gauthier, Serge; Rosa-Neto, Pedro

2014-11-01

Over the past decades, developments in neuroimaging have significantly contributed to the understanding of Alzheimer's disease (AD) pathophysiology. Specifically, positron emission tomography (PET) imaging agents targeting amyloid deposition have provided unprecedented opportunities for refining in vivo diagnosis, monitoring disease propagation, and advancing AD clinical trials. Furthermore, the use of a miniaturized version of PET (microPET) in transgenic (Tg) animals has been a successful strategy for accelerating the development of novel radiopharmaceuticals. However, advanced applications of microPET focusing on the longitudinal propagation of AD pathophysiology or therapeutic strategies remain in their infancy. This review highlights what we have learned from microPET imaging in Tg models displaying amyloid and tau pathology, and anticipates cutting-edge applications with high translational value to clinical research. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Ethical Considerations for Clinical Trials in Inflammatory Bowel Disease

PubMed Central

Becker, Samuel; Siegler, Mark

2014-01-01

Although advancements in the field of inflammatory bowel disease (IBD) include effective therapies for many patients with Crohn’s disease and ulcerative colitis, there remains a large unmet need, and there is a large number of investigational agents in the pipeline. Drug development through clinical trials is critical to understanding the safety and efficacy of new therapies in the affected human population, and the need for ethical trial design is of the utmost importance. This paper explores the ethical issues of clinical trials in IBD, focusing on placebo-controlled trials, vulnerable patients, exposure to monoclonal antibodies, globalization of trials, and surgical advances. PMID:24799837

Advances in bioartificial liver assist devices.

PubMed

Patzer, J F

2001-11-01

Rapid advances in development of bioartificial liver assist devices (BLADs) are exciting clinical interest in the application of BLAD technology for support of patients with acute liver failure. Four devices (Circe Biomedical HepatAssist, Vitagen ELAD, Gerlach BELS, and Excorp Medical BLSS) that rely on hepatocytes cultured in hollow-fiber membrane technology are currently in various stages of clinical evaluation. Several alternative approaches for culture and perfusion of hepatocytes have been evaluated in preclinical, large animal models of liver failure, or at a laboratory scale. Engineering design issues with respect to xenotransplantation, BLAD perfusion, hepatocyte functionality and culture maintenance, and ultimate distribution of a BLAD to a clinical site are delineated.

MAESTRO: Methods and Advanced Equipment for Simulation and Treatment in Radio-Oncology

NASA Astrophysics Data System (ADS)

Barthe, Jean; Hugon, Régis; Nicolai, Jean Philippe

2007-12-01

The integrated project MAESTRO (Methods and Advanced Equipment for Simulation and Treatment in Radio-Oncology) under contract with the European Commission in life sciences FP6 (LSHC-CT-2004-503564), concerns innovative research to develop and validate in clinical conditions, advanced methods and equipment needed in cancer treatment for new modalities in high-conformal external radiotherapy using electrons, photons and protons beams of high energy.

Workplace training for senior trainees: a systematic review and narrative synthesis of current approaches to promote patient safety.

PubMed

Walton, Merrilyn; Harrison, Reema; Burgess, Annette; Foster, Kirsty

2015-10-01

Preventable harm is one of the top six health problems in the developed world. Developing patient safety skills and knowledge among advanced trainee doctors is critical. Clinical supervision is the main form of training for advanced trainees. The use of supervision to develop patient safety competence has not been established. To establish the use of clinical supervision and other workplace training to develop non-technical patient safety competency in advanced trainee doctors. Keywords, synonyms and subject headings were used to search eight electronic databases in addition to hand-searching of relevant journals up to 1 March 2014. Titles and abstracts of retrieved publications were screened by two reviewers and checked by a third. Full-text articles were screened against the eligibility criteria. Data on design, methods and key findings were extracted. Clinical supervision documents were assessed against components common to established patient safety frameworks. Findings from the reviewed articles and document analysis were collated in a narrative synthesis. Clinical supervision is not identified as an avenue for embedding patient safety skills in the workplace and is consequently not evaluated as a method to teach trainees these skills. Workplace training in non-technical patient safety skills is limited, but one-off training courses are sometimes used. Clinical supervision is the primary avenue for learning in postgraduate medical education but the most overlooked in the context of patient safety learning. The widespread implementation of short courses is not matched by evidence of rigorous evaluation. Supporting supervisors to identify teaching moments during supervision and to give weight to non-technical skills and technical skills equally is critical. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Describing the implementation of an innovative intervention and evaluating its effectiveness in increasing research capacity of advanced clinical nurses: using the consolidated framework for implementation research.

PubMed

McKee, Gabrielle; Codd, Margaret; Dempsey, Orla; Gallagher, Paul; Comiskey, Catherine

2017-01-01

Despite advanced nursing roles having a research competency, participation in research is low. There are many barriers to participation in research and few interventions have been developed to address these. This paper aims to describe the implementation of an intervention to increase research participation in advanced clinical nursing roles and evaluate its effectiveness. The implementation of the intervention was carried out within one hospital site. The evaluation utilised a mixed methods design and a implementation science framework. All staff in advanced nursing roles were invited to take part, all those who were interested and had a project in mind could volunteer to participate in the intervention. The intervention consisted of the development of small research groups working on projects developed by the nurse participant/s and supported by an academic and a research fellow. The main evaluation was through focus groups. Output was analysed using thematic analysis. In addition, a survey questionnaire was circulated to all participants to ascertain their self-reported research skills before and after the intervention. The results of the survey were analysed using descriptive statistics. Finally an inventory of research outputs was collated. In the first year, twelve new clinical nurse-led research projects were conducted and reported in six peer reviewed papers, two non-peer reviewed papers and 20 conference presentations. The main strengths of the intervention were its promptness to complete research, to publish and to showcase clinical innovations. Main barriers identified were time, appropriate support from academics and from peers. The majority of participants had increased experience at scientific writing and data analysis. This study shows that an intervention, with minor financial resources; a top down approach; support of a hands on research fellow; peer collaboration with academics; strong clinical ownership by the clinical nurse researcher; experiential learning opportunities; focused and with needs based educational sessions, is an intervention that can both increase research outputs and capacity of clinically based nurses. Interventions to further enhance nursing research and their evaluation are crucial if we are to address the deficit of nurse-led patient-centred research in the literature.

Systemic therapy for unresectable and metastatic transitional cell carcinoma of the urothelium: first-line and beyond.

PubMed

Cheng, Tina

2008-09-01

The review aims to provide an overview of recent advances and future research direction in the management of patients with advanced transitional cell carcinoma. Early data of the randomized phase III study comparing paclitaxel, cisplatin, and gemcitabine with gemcitabine plus cisplatin for advanced urothelial cancer detected no survival difference. A phase II study investigated the safety and efficacy of trastuzumab, carboplatin, gemcitabine, and paclitaxel in human epidermal growth factor receptor-2/neu-positive advanced urothelial carcinoma and reported promising results. Renal-sparing regimens are under active development. A nonrandomized comparison of the 3-week with the 4-week schedule for gemcitabine and cisplatin showed that the 3-week schedule had less hematological toxicity and better dose intensity. Potential molecular markers such as excision repair cross-complementation group 1, emmprin, and survivin for survival and/or platinum resistance in patients with transitional cell carcinoma showed promise. Recent data do not support change in the current standard of care for advanced transitional cell carcinoma. Clinical testing of emerging anticancer therapies using new agents, new combinations, and new approaches is under active investigation. Rational combination and new strategy in clinical trial design are critical for new drug development for transitional cell carcinoma.

Plant-made vaccine antigens and biopharmaceuticals

PubMed Central

Daniell, Henry; Singh, Nameirakpam D.; Mason, Hugh; Streatfield, Stephen J.

2009-01-01

Plant cells are ideal bioreactors for the production and oral delivery of vaccines and biopharmaceuticals, eliminating the need for expensive fermentation, purification, cold storage, transportation and sterile delivery. Plant-made vaccines have been developed for two decades but none has advanced beyond Phase I. However, two plant-made biopharmaceuticals are now advancing through Phase II and Phase III human clinical trials. In this review, we evaluate the advantages and disadvantages of different plant expression systems (stable nuclear and chloroplast or transient viral) and their current limitations or challenges. We provide suggestions for advancing this valuable concept for clinical applications and conclude that greater research emphasis is needed on large scale production, purification, functional characterization, oral delivery and preclinical evaluation. PMID:19836291

Biomedical informatics research network: building a national collaboratory to hasten the derivation of new understanding and treatment of disease.

PubMed

Grethe, Jeffrey S; Baru, Chaitan; Gupta, Amarnath; James, Mark; Ludaescher, Bertram; Martone, Maryann E; Papadopoulos, Philip M; Peltier, Steven T; Rajasekar, Arcot; Santini, Simone; Zaslavsky, Ilya N; Ellisman, Mark H

2005-01-01

Through support from the National Institutes of Health's National Center for Research Resources, the Biomedical Informatics Research Network (BIRN) is pioneering the use of advanced cyberinfrastructure for medical research. By synchronizing developments in advanced wide area networking, distributed computing, distributed database federation, and other emerging capabilities of e-science, the BIRN has created a collaborative environment that is paving the way for biomedical research and clinical information management. The BIRN Coordinating Center (BIRN-CC) is orchestrating the development and deployment of key infrastructure components for immediate and long-range support of biomedical and clinical research being pursued by domain scientists in three neuroimaging test beds.

A qualitative study of advanced nurse practitioners' use of physical assessment skills in the community: shifting skills across professional boundaries.

PubMed

Raleigh, Mary; Allan, Helen

2017-07-01

To explore multiple perspectives on the use of physical assessment skills by advanced nurse practitioners in the UK. Physical assessment skills practices are embedded in advanced nursing practice roles in the UK. There is little evidence on how these skills are used by advanced nurse practitioners in the community. Case study. A qualitative interpretative single-embedded case study of 22 participants from South of England. A framework method analysed interview data collected by the researcher between March-August 2013. Participants included nurses, doctors, nurse educators and managers. Physical assessment skills education at universities is part of a policy shift to develop a flexible workforce in the UK. Shared physical assessment practices are less to do with role substitution and more about preparing practitioners with skills that are fit for purpose. Competence, capability and performance with physical assessment skills are an expectation of advanced nursing practice. These skills are used successfully by community advanced nurse practitioners to deliver a wide range of services in response to changing patient need. The introduction of physical assessment skills education to undergraduate professional preparation would create a firm foundation to develop these skills in postgraduate education. Physical assessment education prepares nurses with the clinical competencies to carry out healthcare reforms in the UK. Shared sets of clinical assessment competencies between disciplines have better outcomes for patients. Levels of assessment competence can depend on the professional attributes of individual practitioners. Unsupportive learning cultures can hinder professional development of advanced nursing practice. © 2016 John Wiley & Sons Ltd.

CCR5 receptor antagonists in preclinical to phase II clinical development for treatment of HIV

PubMed Central

Kim, Michelle B.; Giesler, Kyle E.; Tahirovic, Yesim A.; Truax, Valarie M.; Liotta, Dennis C.; Wilson, Lawrence J.

2018-01-01

Introduction The chemokine receptor CCR5 has garnered significant attention in recent years as a target to treat HIV infection largely due to the approval and success of the drug Maraviroc. The side effects and inefficiencies with other first generation agents led to failed clinical trials, prompting the development of newer CCR5 antagonists. Areas covered This review aims to survey the current status of ‘next generation’ CCR5 antagonists in the preclinical pipeline with an emphasis on emerging agents for the treatment of HIV infection. These efforts have culminated in the identification of advanced second-generation agents to reach the clinic and the dual CCR5/CCR2 antagonist Cenicriviroc as the most advanced currently in phase II clinical studies. Expert opinion The clinical success of CCR5 inhibitors for treatment of HIV infection has rested largely on studies of Maraviroc and a second-generation dual CCR5/CCR2 antagonist Cenicriviroc. Although research efforts identified several promising preclinical candidates, these were dropped during early clinical studies. Despite patient access to Maraviroc, there is insufficient enthusiasm surrounding its use as front-line therapy for treatment of HIV. The non-HIV infection related development activities for Maraviroc and Cenicriviroc may help drive future interests. PMID:27791451

Clinical Research Informatics for Big Data and Precision Medicine.

PubMed

Weng, C; Kahn, M G

2016-11-10

To reflect on the notable events and significant developments in Clinical Research Informatics (CRI) in the year of 2015 and discuss near-term trends impacting CRI. We selected key publications that highlight not only important recent advances in CRI but also notable events likely to have significant impact on CRI activities over the next few years or longer, and consulted the discussions in relevant scientific communities and an online living textbook for modern clinical trials. We also related the new concepts with old problems to improve the continuity of CRI research. The highlights in CRI in 2015 include the growing adoption of electronic health records (EHR), the rapid development of regional, national, and global clinical data research networks for using EHR data to integrate scalable clinical research with clinical care and generate robust medical evidence. Data quality, integration, and fusion, data access by researchers, study transparency, results reproducibility, and infrastructure sustainability are persistent challenges. The advances in Big Data Analytics and Internet technologies together with the engagement of citizens in sciences are shaping the global clinical research enterprise, which is getting more open and increasingly stakeholder-centered, where stakeholders include patients, clinicians, researchers, and sponsors.

Clinical Research Informatics for Big Data and Precision Medicine

PubMed Central

Kahn, M. G.

2016-01-01

Summary Objectives To reflect on the notable events and significant developments in Clinical Research Informatics (CRI) in the year of 2015 and discuss near-term trends impacting CRI. Methods We selected key publications that highlight not only important recent advances in CRI but also notable events likely to have significant impact on CRI activities over the next few years or longer, and consulted the discussions in relevant scientific communities and an online living textbook for modern clinical trials. We also related the new concepts with old problems to improve the continuity of CRI research. Results The highlights in CRI in 2015 include the growing adoption of electronic health records (EHR), the rapid development of regional, national, and global clinical data research networks for using EHR data to integrate scalable clinical research with clinical care and generate robust medical evidence. Data quality, integration, and fusion, data access by researchers, study transparency, results reproducibility, and infrastructure sustainability are persistent challenges. Conclusion The advances in Big Data Analytics and Internet technologies together with the engagement of citizens in sciences are shaping the global clinical research enterprise, which is getting more open and increasingly stakeholder-centered, where stakeholders include patients, clinicians, researchers, and sponsors. PMID:27830253

Coherent anti-Stokes Raman scattering microscopy: overcoming technical barriers for clinical translation

PubMed Central

Tu, Haohua; Boppart, Stephen A.

2015-01-01

Clinical translation of coherent anti-Stokes Raman scattering microscopy is of great interest because of the advantages of noninvasive label-free imaging, high sensitivity, and chemical specificity. For this to happen, we have identified and review the technical barriers that must be overcome. Prior investigations have developed advanced techniques (features), each of which can be used to effectively overcome one particular technical barrier. However, the implementation of one or a small number of these advanced features in previous attempts for clinical translation has often introduced more tradeoffs than benefits. In this review, we outline a strategy that would integrate multiple advanced features to overcome all the technical barriers simultaneously, effectively reduce tradeoffs, and synergistically optimize CARS microscopy for clinical translation. The operation of the envisioned system incorporates coherent Raman micro-spectroscopy for identifying vibrational biomolecular markers of disease and single-frequency (or hyperspectral) Raman imaging of these specific biomarkers for real-time in vivo diagnostics and monitoring. An optimal scheme of clinical CARS micro-spectroscopy for thin ex vivo tissues. PMID:23674234

Office Overview | Office of Cancer Clinical Proteomics Research

Cancer.gov

The Office of Cancer Clinical Proteomics Research (OCCPR) at the National Cancer Institute (NCI) aims to improve prevention, early detection, diagnosis, and treatment of cancer by enhancing the understanding of the molecular mechanisms of cancer, advancing proteome/proteogenome science and technology development through community resources (data and reagents), and accelerating the translation of molecular findings into the clinic.

Linking international research to global health equity: the limited contribution of bioethics.

PubMed

Pratt, Bridget; Loff, Bebe

2013-05-01

Health research has been identified as a vehicle for advancing global justice in health. However, in bioethics, issues of global justice are mainly discussed within an ongoing debate on the conditions under which international clinical research is permissible. As a result, current ethical guidance predominantly links one type of international research (biomedical) to advancing one aspect of health equity (access to new treatments). International guidelines largely fail to connect international research to promoting broader aspects of health equity - namely, healthier social environments and stronger health systems. Bioethical frameworks such as the human development approach do consider how international clinical research is connected to the social determinants of health but, again, do so to address the question of when international clinical research is permissible. It is suggested that the narrow focus of this debate is shaped by high-income countries' economic strategies. The article further argues that the debate's focus obscures a stronger imperative to consider how other types of international research might advance justice in global health. Bioethics should consider the need for non-clinical health research and its contribution to advancing global justice. © 2011 Blackwell Publishing Ltd.

Advances in Oral Appliances for Obstructive Sleep Apnea.

PubMed

Jacobowitz, Ofer

2017-01-01

Oral appliances that advance the mandible are widely used as alternatives to positive airway pressure (PAP) devices or as primary therapy for obstructive sleep apnea (OSA) in adults. Although PAP is more efficacious at lowering the polysomnographic indices of OSA, the clinical effectiveness of PAP and oral appliances is similar, and patients are more likely to adhere to oral appliance therapy than to PAP treatment. Clinical examination is used to determine the candidacy of oral appliances and to select a particular appliance for a given patient. Endoscopic examination of the pharynx may be used to help assess the potential for efficacy. Otherwise, if available, titration of mandibular protrusion during sleep may be performed prior to appliance production in order to assess efficacy. Once a patient is fitted with a titratable oral appliance, further advancement is usually performed at home to resolve the clinical symptoms and signs of OSA. Clinical follow-up is needed to assess the outcome, side effects, and adherence, as the long-term adherence rate is approximately 50%. Recent advances in oral appliance therapy include the development of embedded temperature sensors for adherence monitoring and the production of thinner, lighter appliances via 3D printing techniques. © 2017 S. Karger AG, Basel.

Historical Perspective on Mitochondrial Medicine

ERIC Educational Resources Information Center

DiMauro, Salvatore; Garone, Caterina

2010-01-01

In this review, we trace the origins and follow the development of mitochondrial medicine from the premolecular era (1962-1988) based on clinical clues, muscle morphology, and biochemistry into the molecular era that started in 1988 and is still advancing at a brisk pace. We have tried to stress conceptual advances, such as endosymbiosis,…

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

PubMed Central

Tosi, Umberto; Marnell, Christopher S.; Chang, Raymond; Cho, William C.; Ting, Richard; Maachani, Uday B.; Souweidane, Mark M.

2017-01-01

Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents. PMID:28208698

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors.

PubMed

Tosi, Umberto; Marnell, Christopher S; Chang, Raymond; Cho, William C; Ting, Richard; Maachani, Uday B; Souweidane, Mark M

2017-02-08

Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood-brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a "wait-and-see" approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents.

Management of Locally Advanced Cancer Cervix an Indian Perspective.

PubMed

Singh, J K; Chauhan, Richa

2015-01-01

Cervical cancer has a major impact on the lives of Indian women with an estimated 122, 844 new cases of cervical cancer in the year 2012. About 80% of these cases present in a locally advanced stage leading to high morbidity and mortality. Because of lack of public awareness and infrastructure for screening and early detection in developing countries, this late presentation is likely to continue in the coming years. Radiation therapy has been the treatment of choice for patients with locally advanced cancer cervix. Many clinical trials and meta-analyses have shown a significant improvement in overall and progression-free survival with decreased local and distant recurrences with the use of concurrent chemotherapy with radiation. Most of these trials have been done in women from developed countries where the patient and disease profile are entirely different from ours. Recently, few trials from India have also shown promising results in locally advanced cancer cervix with concurrent chemoradiotherapy but toxicities remain a major concern. Further exploration is required for the use of concurrent chemo radiation prior to incorporating it into routine clinical practice.

Laser immunotherapy for treatment of patients with advanced breast cancer and melanoma

NASA Astrophysics Data System (ADS)

Li, Xiaosong; Hode, Tomas; Guerra, Maria C.; Ferrel, Gabriela L.; Nordquist, Robert E.; Chen, Wei R.

2011-02-01

Laser immunotherapy (LIT) was developed for the treatment of metastatic tumors. It combines local selective photothermal interaction and active immunological stimulation to induce a long-term, systemic anti-tumor immunity. During the past sixteen years, LIT has been advanced from bench-top to bedside, with promising outcomes. In our pre-clinical and preliminary clinical studies, LIT has demonstrated the capability in inducing immunological responses, which not only can eradicate the treated primary tumors, but also can eliminate untreated metastases at distant sites. Specifically, LIT has been used to treat advanced melanoma and breast cancer patients during the past five years. LIT was shown to be effective in controlling both primary tumors and distant metastases in late-stage patients, who have failed conventional therapies such as surgery, chemotherapy, radiation, and other more advanced approaches. The methodology and the development of LIT are presented in this paper. The patients' responses to LIT are also reported in this paper. The preliminary results obtained in these studies indicated that LIT could be an effective modality for the treatment of patients with late-stage, metastatic cancers, who are facing severely limited options.

Mesenchymal Stem Cells in Lipogems, a Reverse Story: from Clinical Practice to Basic Science.

PubMed

Tremolada, Carlo; Ricordi, Camillo; Caplan, Arnold I; Ventura, Carlo

2016-01-01

The idea that basic science should be the starting point for modern clinical approaches has been consolidated over the years, and emerged as the cornerstone of Molecular Medicine. Nevertheless, there is increasing concern over the low efficiency and inherent costs related to the translation of achievements from the bench to the bedside. These burdens are also perceived with respect to the effectiveness of translating basic discoveries in stem cell biology to the newly developing field of advanced cell therapy or Regenerative Medicine. As an alternative paradigm, past and recent history in Medical Science provides remarkable reverse stories in which clinical observations at the patient's bedside have fed major advances in basic research which, in turn, led to consistent progression in clinical practice. Within this context, we discuss our recently developed method and device, which forms the core of a system (Lipogems) for processing of human adipose tissue solely with the aid of mild mechanical forces to yield a microfractured tissue product.

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.

The need for clinical quantification of combined PET/MRI data in pediatric epilepsy

NASA Astrophysics Data System (ADS)

Muzik, Otto; Pai, Darshan; Juhasz, Csaba; Hua, Jing

2013-02-01

In the past, multimodality integrative analysis of image data has been used to obtain a better understanding of underlying mechanisms of seizure generation and propagation in children with extratemporal lobe epilepsy. However, despite important advances in the combined analysis of PET, MRI, DTI and EEG data, successful surgical outcome is only achieved in about 2/3 of patients undergoing resective surgery. The advent of simultaneous PET/MR data acquisition promises an important advance in neuroimaging through clinical quantification, which will finally translate the strength of PET (which is the ability to absolutely quantify physiological parameters such as metabolic rates and receptor densities) into clinical work. Taking advantage of recently developed integrated PET/MR devices, absolute physiological values will be available in clinical routine, replacing currently used visual assessment of relative tissue tracer uptake. This will allow assessment of global increases/decreases of brain function during critical phases of development and is likely to have a significant impact on patient management in pediatric epilepsy.

Recent Developments in PET Instrumentation

PubMed Central

Peng, Hao; Levin, Craig S.

2013-01-01

Positron emission tomography (PET) is used in the clinic and in vivo small animal research to study molecular processes associated with diseases such as cancer, heart disease, and neurological disorders, and to guide the discovery and development of new treatments. This paper reviews current challenges of advancing PET technology and some of newly developed PET detectors and systems. The paper focuses on four aspects of PET instrumentation: high photon detection sensitivity; improved spatial resolution; depth-of-interaction (DOI) resolution and time-of-flight (TOF). Improved system geometry, novel non-scintillator based detectors, and tapered scintillation crystal arrays are able to enhance the photon detection sensitivity of a PET system. Several challenges for achieving high resolution with standard scintillator-based PET detectors are discussed. Novel detectors with 3-D positioning capability have great potential to be deployed in PET for achieving spatial resolution better than 1 mm, such as cadmium-zinc-telluride (CZT) and position-sensitive avalanche photodiodes (PSAPDs). DOI capability enables a PET system to mitigate parallax error and achieve uniform spatial resolution across the field-of-view (FOV). Six common DOI designs, as well as advantages and limitations of each design, are discussed. The availability of fast scintillation crystals such as LaBr3, and the silicon photomultiplier (SiPM) greatly advances TOF-PET development. Recent instrumentation and initial results of clinical trials are briefly presented. If successful, these technology advances, together with new probe molecules, will substantially enhance the molecular sensitivity of PET and thus increase its role in preclinical and clinical research as well as evaluating and managing disease in the clinic. PMID:20497121

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

[To see the future development of burn medicine from the view of holistic integrative medicine].

PubMed

Hu, D H; Tao, K

2017-04-20

The therapeutic methods and effects have been improved greatly in the past few decades for burn care and management with several important advancements which have resulted in more effective patient stabilization and significantly decreased mortality in China. However, the challenges still exist, such as how to further improve the recovery of the patients' appearance and function, and how to advance the treatment of severe deep extensive burn injury, etc. The theory of holistic integrative medicine (HIM) provides a new opportunity for the development of clinical medicine. This article emphasizes the important roles of HIM in exploration of burn medicine, considering the advanced development of modern life sciences and relevant techniques.

The impact of new trends in POCTs for companion diagnostics, non-invasive testing and molecular diagnostics.

PubMed

Huckle, David

2015-06-01

Point-of-care diagnostics have been slowly developing over several decades and have taken on a new importance in current healthcare delivery for both diagnostics and development of new drugs. Molecular diagnostics have become a key driver of technology change and opened up new areas in companion diagnostics for use alongside pharmaceuticals and in new clinical approaches such as non-invasive testing. Future areas involving smartphone and other information technology advances, together with new developments in molecular biology, microfluidics and surface chemistry are adding to advances in the market. The focus for point-of-care tests with molecular diagnostic technologies is focused on advancing effective applications.

Advancing tuberculosis drug regimen development through innovative quantitative translational pharmacology methods and approaches.

PubMed

Hanna, Debra; Romero, Klaus; Schito, Marco

2017-03-01

The development of novel tuberculosis (TB) multi-drug regimens that are more efficacious and of shorter duration requires a robust drug development pipeline. Advances in quantitative modeling and simulation can be used to maximize the utility of patient-level data from prior and contemporary clinical trials, thus optimizing study design for anti-TB regimens. This perspective article highlights the work of seven project teams developing first-in-class translational and quantitative methodologies that aim to inform drug development decision-making, dose selection, trial design, and safety assessments, in order to achieve shorter and safer therapies for patients in need. These tools offer the opportunity to evaluate multiple hypotheses and provide a means to identify, quantify, and understand relevant sources of variability, to optimize translation and clinical trial design. When incorporated into the broader regulatory sciences framework, these efforts have the potential to transform the development paradigm for TB combination development, as well as other areas of global health. Copyright © 2016. Published by Elsevier Ltd.

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.

Dystonia.

PubMed

De Pablo-Fernandez, Eduardo; Warner, Thomas T

2017-09-01

Dystonia is a clinically heterogeneous group of hyperkinetic movement disorders. Recent advances have provided a better understanding of these conditions with significant clinical impact. Peer reviewed journals and reviews. PubMed.gov. A recent consensus classification, including the assessment of phenomenology and identification of the dystonia syndromes, has provided a helpful tool for the clinical assessment. New forms of monogenic dystonia have been recently identified. Despite recent advances in the understanding of dystonia, treatment remains symptomatic in most patients. Recent advances in genetics have provided a better understanding of the potential pathogenic mechanisms involved in dystonia. Deep brain stimulation has shown to improve focal and combined forms of dystonia and its indications are constantly expanding. Growing understanding of the disease mechanisms involved will allow the development of targeted and disease-modifying therapies in the future. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Realization of Real-Time Clinical Data Integration Using Advanced Database Technology

PubMed Central

Yoo, Sooyoung; Kim, Boyoung; Park, Heekyong; Choi, Jinwook; Chun, Jonghoon

2003-01-01

As information & communication technologies have advanced, interest in mobile health care systems has grown. In order to obtain information seamlessly from distributed and fragmented clinical data from heterogeneous institutions, we need solutions that integrate data. In this article, we introduce a method for information integration based on real-time message communication using trigger and advanced database technologies. Messages were devised to conform to HL7, a standard for electronic data exchange in healthcare environments. The HL7 based system provides us with an integrated environment in which we are able to manage the complexities of medical data. We developed this message communication interface to generate and parse HL7 messages automatically from the database point of view. We discuss how easily real time data exchange is performed in the clinical information system, given the requirement for minimum loading of the database system. PMID:14728271

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

Quantitative Imaging in Cancer Clinical Trials

PubMed Central

Yankeelov, Thomas E.; Mankoff, David A.; Schwartz, Lawrence H.; Lieberman, Frank S.; Buatti, John M.; Mountz, James M.; Erickson, Bradley J.; Fennessy, Fiona M.M.; Huang, Wei; Kalpathy-Cramer, Jayashree; Wahl, Richard L.; Linden, Hannah M.; Kinahan, Paul; Zhao, Binsheng; Hylton, Nola M.; Gillies, Robert J.; Clarke, Laurence; Nordstrom, Robert; Rubin, Daniel L.

2015-01-01

As anti-cancer therapies designed to target specific molecular pathways have been developed, it has become critical to develop methods to assess the response induced by such agents. While traditional, anatomic CT and MRI exams are useful in many settings, there is increasing evidence that these methods cannot answer the fundamental biological and physiological questions essential for assessment and, eventually, prediction of treatment response in the clinical trial setting, especially in the critical period soon after treatment is initiated. To optimally apply advances in quantitative imaging methods to trials of targeted cancer therapy, new infrastructure improvements are needed that incorporate these emerging techniques into the settings where they are most likely to have impact. In this review, we first elucidate the needs for therapeutic response assessment in the era of molecularly targeted therapy and describe how quantitative imaging can most effectively provide scientifically and clinically relevant data. We then describe the tools and methods required to apply quantitative imaging and provide concrete examples of work making these advances practically available for routine application in clinical trials. We conclude by proposing strategies to surmount barriers to wider incorporation of these quantitative imaging methods into clinical trials and, eventually, clinical practice. Our goal is to encourage and guide the oncology community to deploy standardized quantitative imaging techniques in clinical trials to further personalize care for cancer patients, and to provide a more efficient path for the development of improved targeted therapies. PMID:26773162

Strengths and Weaknesses of Pre-Clinical Models for Human Melanoma Treatment: Dawn of Dogs’ Revolution for Immunotherapy

PubMed Central

Barutello, Giuseppina; Rolih, Valeria; Arigoni, Maddalena; Tarone, Lidia; Conti, Laura

2018-01-01

Despite several therapeutic advances, malignant melanoma still remains a fatal disease for which novel and long-term curative treatments are needed. The successful development of innovative therapies strongly depends on the availability of appropriate pre-clinical models. For this purpose, several mouse models holding the promise to provide insight into molecular biology and clinical behavior of melanoma have been generated. The most relevant ones and their contribution for the advancement of therapeutic approaches for the treatment of human melanoma patients will be here summarized. However, as models, mice do not recapitulate all the features of human melanoma, thus their strengths and weaknesses need to be carefully identified and considered for the translation of the results into the human clinics. In this panorama, the concept of comparative oncology acquires a priceless value. The revolutionary importance of spontaneous canine melanoma as a translational model for the pre-clinical investigation of melanoma progression and treatment will be here discussed, with a special consideration to the development of innovative immunotherapeutic approaches. PMID:29534457

Self-assessment of clinical nurse mentors as dimensions of professional development and the capability of developing ethical values at nursing students: A correlational research study.

PubMed

Skela-Savič, Brigita; Kiger, Alice

2015-10-01

Providing adequate training for mentors, fostering a positive mentorship culture and establishing the necessary operational procedures for ensuring mentorship quality are the keys to effective clinical mentoring of nursing students. The purpose of the research was to explain different dimensions of clinical mentors' professional development and their capability of developing ethical values in nursing students. A non-experimental quantitative research design was employed. Data were collected by means of a questionnaire administered to the population of clinical mentors (N=143). The total number of questions was 36. Descriptive statistics were used, and bivariate analysis, factor analysis, correlation analysis and linear regression analysis were performed. The professional development of clinical nurse mentors was explained (R(2)=0.256) by career advancement (p=0.000), research and learning (p=0.024) and having a career development plan (p=0.043). Increased professional self-confidence (R(2)=0.188) was explained by career advancement (p=0.000) and the time engaged in record keeping (p=0.028). Responsibility for the development of ethical values in nursing students (R(2)=0.145) was explained by the respondents' level of education (p=0.020) and research and learning (p=0.024). Applying ethical principles and norms into practice (R(2)=0.212) was explained by self-assessed knowledge in ethics (p=0.037) and research and learning (p=0.044). Clinical nurse mentors tended to lack a career development plan, had low work time spent on research and insufficiently participated in education and training activities, which turned out to be significant explanatory factors of their professional development and their capability of developing ethical values in nursing students. The research showed that nursing and higher education managers often failed to assume responsibility for the professional development of clinical nurse mentors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinical software development for the Web: lessons learned from the BOADICEA project

PubMed Central

2012-01-01

Background In the past 20 years, society has witnessed the following landmark scientific advances: (i) the sequencing of the human genome, (ii) the distribution of software by the open source movement, and (iii) the invention of the World Wide Web. Together, these advances have provided a new impetus for clinical software development: developers now translate the products of human genomic research into clinical software tools; they use open-source programs to build them; and they use the Web to deliver them. Whilst this open-source component-based approach has undoubtedly made clinical software development easier, clinical software projects are still hampered by problems that traditionally accompany the software process. This study describes the development of the BOADICEA Web Application, a computer program used by clinical geneticists to assess risks to patients with a family history of breast and ovarian cancer. The key challenge of the BOADICEA Web Application project was to deliver a program that was safe, secure and easy for healthcare professionals to use. We focus on the software process, problems faced, and lessons learned. Our key objectives are: (i) to highlight key clinical software development issues; (ii) to demonstrate how software engineering tools and techniques can facilitate clinical software development for the benefit of individuals who lack software engineering expertise; and (iii) to provide a clinical software development case report that can be used as a basis for discussion at the start of future projects. Results We developed the BOADICEA Web Application using an evolutionary software process. Our approach to Web implementation was conservative and we used conventional software engineering tools and techniques. The principal software development activities were: requirements, design, implementation, testing, documentation and maintenance. The BOADICEA Web Application has now been widely adopted by clinical geneticists and researchers. BOADICEA Web Application version 1 was released for general use in November 2007. By May 2010, we had > 1200 registered users based in the UK, USA, Canada, South America, Europe, Africa, Middle East, SE Asia, Australia and New Zealand. Conclusions We found that an evolutionary software process was effective when we developed the BOADICEA Web Application. The key clinical software development issues identified during the BOADICEA Web Application project were: software reliability, Web security, clinical data protection and user feedback. PMID:22490389

Clinical software development for the Web: lessons learned from the BOADICEA project.

PubMed

Cunningham, Alex P; Antoniou, Antonis C; Easton, Douglas F

2012-04-10

In the past 20 years, society has witnessed the following landmark scientific advances: (i) the sequencing of the human genome, (ii) the distribution of software by the open source movement, and (iii) the invention of the World Wide Web. Together, these advances have provided a new impetus for clinical software development: developers now translate the products of human genomic research into clinical software tools; they use open-source programs to build them; and they use the Web to deliver them. Whilst this open-source component-based approach has undoubtedly made clinical software development easier, clinical software projects are still hampered by problems that traditionally accompany the software process. This study describes the development of the BOADICEA Web Application, a computer program used by clinical geneticists to assess risks to patients with a family history of breast and ovarian cancer. The key challenge of the BOADICEA Web Application project was to deliver a program that was safe, secure and easy for healthcare professionals to use. We focus on the software process, problems faced, and lessons learned. Our key objectives are: (i) to highlight key clinical software development issues; (ii) to demonstrate how software engineering tools and techniques can facilitate clinical software development for the benefit of individuals who lack software engineering expertise; and (iii) to provide a clinical software development case report that can be used as a basis for discussion at the start of future projects. We developed the BOADICEA Web Application using an evolutionary software process. Our approach to Web implementation was conservative and we used conventional software engineering tools and techniques. The principal software development activities were: requirements, design, implementation, testing, documentation and maintenance. The BOADICEA Web Application has now been widely adopted by clinical geneticists and researchers. BOADICEA Web Application version 1 was released for general use in November 2007. By May 2010, we had > 1200 registered users based in the UK, USA, Canada, South America, Europe, Africa, Middle East, SE Asia, Australia and New Zealand. We found that an evolutionary software process was effective when we developed the BOADICEA Web Application. The key clinical software development issues identified during the BOADICEA Web Application project were: software reliability, Web security, clinical data protection and user feedback.

Update: the status of clinical trials with kinase inhibitors in thyroid cancer.

PubMed

Wells, Samuel A; Santoro, Massimo

2014-05-01

Thyroid cancer is usually cured by timely thyroidectomy; however, the treatment of patients with advanced disease is challenging because their tumors are mostly unresponsive to conventional therapies. Recently, the malignancy has attracted much interest for two reasons: the dramatic increase in its incidence over the last three decades, and the discovery of the genetic mutations or chromosomal rearrangements causing most histological types of thyroid cancer. This update reviews the molecular genetics of thyroid cancer and the clinical trials evaluating kinase inhibitors (KIs) in patients with locally advanced or metastatic disease. The update also reviews studies in other malignancies, which have identified mechanisms of efficacy, and also resistance, to specific KIs. This information has been critical both to the development of effective second-generation drugs and to the design of combinatorial therapeutic regimens. Finally, the update addresses the major challenges facing clinicians who seek to develop more effective therapy for patients with thyroid cancer. PubMed was searched from January 2000 to November 2013 using the following terms: thyroid cancer, treatment of thyroid cancer, clinical trials in thyroid cancer, small molecule therapeutics, kinase inhibitors, and next generation sequencing. A new era in cancer therapy has emerged based on the introduction of KIs for the treatment of patients with liquid and solid organ malignancies. Patients with thyroid cancer have benefited from this advance and will continue to do so with the development of drugs having greater specificity and with the implementation of clinical trials of combined therapeutics to overcome drug resistance.

Application development environment for advanced digital workstations

NASA Astrophysics Data System (ADS)

Valentino, Daniel J.; Harreld, Michael R.; Liu, Brent J.; Brown, Matthew S.; Huang, Lu J.

1998-06-01

One remaining barrier to the clinical acceptance of electronic imaging and information systems is the difficulty in providing intuitive access to the information needed for a specific clinical task (such as reaching a diagnosis or tracking clinical progress). The purpose of this research was to create a development environment that enables the design and implementation of advanced digital imaging workstations. We used formal data and process modeling to identify the diagnostic and quantitative data that radiologists use and the tasks that they typically perform to make clinical decisions. We studied a diverse range of radiology applications, including diagnostic neuroradiology in an academic medical center, pediatric radiology in a children's hospital, screening mammography in a breast cancer center, and thoracic radiology consultation for an oncology clinic. We used object- oriented analysis to develop software toolkits that enable a programmer to rapidly implement applications that closely match clinical tasks. The toolkits support browsing patient information, integrating patient images and reports, manipulating images, and making quantitative measurements on images. Collectively, we refer to these toolkits as the UCLA Digital ViewBox toolkit (ViewBox/Tk). We used the ViewBox/Tk to rapidly prototype and develop a number of diverse medical imaging applications. Our task-based toolkit approach enabled rapid and iterative prototyping of workstations that matched clinical tasks. The toolkit functionality and performance provided a 'hands-on' feeling for manipulating images, and for accessing textual information and reports. The toolkits directly support a new concept for protocol based-reading of diagnostic studies. The design supports the implementation of network-based application services (e.g., prefetching, workflow management, and post-processing) that will facilitate the development of future clinical applications.

Innovation in organ transplantation: A meeting report.

PubMed

Fishman, Jay A; Greenwald, Melissa

2018-05-09

This workshop targeted opportunities to stimulate transformative innovation in organ transplantation. Participants reached consensus regarding the following: (1) Mechanisms are needed to improve the coordination of policy and oversight activities, given overlapping responsibilities for transplantation and clinical investigation among federal agencies. Innovative clinical trials span traditional administrative boundaries and include stakeholders with diverse interests. Participants identified the need for a governmental interagency working group to coordinate nationwide transplant-related activities. (2) Improvements are required in clinical metrics for transplantation, with alignment of performance goals across transplantation organizations and any development of data requirements being consistent with those goals. Database coordination among clinical centers, organ procurement organizations, regulatory agencies, and payers would facilitate research and better inform policy. New data requirements should provide actionable insights into clinical performance. (3) Innovative research seen as potentially adversely affecting Program-Specific Reports may reduce centers' participation. Cutting-edge research requires mitigation of risk-aversive behaviors created by reporting of clinical outcomes data. Participants proposed a new review process in advance of implementation of clinical trials to guide "carve-outs" of transplant center outcomes data from Program-Specific Reports. Clinical transplantation will be advanced by the development of a shared and comprehensive research agenda to facilitate coordination of research and policy. © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.

Recent advances and future challenges in cancer immunotherapy.

PubMed

Okuyama, Namiko; Tamada, Koji; Tamura, Hideto

2016-01-01

Remarkable advances have been made in cancer immunotherapy. Recent treatment strategies, especially chimeric antigen receptor-T (CAR-T) cell therapy and immune checkpoint inhibitors, reportedly achieve higher objective responses and better survival rates than previous immunotherapies for patients with treatment-resistant malignancies, creating a paradigm shift in cancer treatment. Several clinical trials of cancer immunotherapy for patients with various malignancies are ongoing. However, those with certain malignancies, such as low-immunogenic cancers, cannot be successfully treated with T-cell immunotherapy, and subsets of immunotherapy-treated patients relapse, meaning that more effective immunotherapeutic strategies are needed for such patients. Furthermore, the safety, convenience, and cost of cancer immunotherapy need to be improved in the near future. Herein, we discuss recent advances and future challenges in cancer immunotherapy, i.e., the identification of neoantigens for the development of individualized immunotherapies, the development of new CAR-T cell therapies, including so-called armored CAR-T cells that can induce greater clinical effects and thereby achieve longer survival, the development of off-the-shelf treatment regimens using non-self cells or cell lines, and effective cancer immunotherapy combinations.

Advanced and recurring thymic carcinoma is target of new clinical trial | Center for Cancer Research

Cancer.gov

Adults diagnosed with thymic carcinoma who overexpress the protein mesothelin may be eligible to participate in a new clinical trial at the NIH Clinical Center. The study will look at the safety and effectiveness of an investigational drug, anetumab ravtansine, developed by Bayer HealthCare Pharmaceuticals. The drug works by binding to mesothelin, therefore overexpression of

Advancing pharmacometrics and systems pharmacology.

PubMed

Waldman, S A; Terzic, A

2012-11-01

Pharmacometrics and systems pharmacology are emerging as principal quantitative sciences within drug development and experimental therapeutics. In recognition of the importance of pharmacometrics and systems pharmacology to the discipline of clinical pharmacology, the American Society for Clinical Pharmacology and Therapeutics (ASCPT), in collaboration with Nature Publishing Group and Clinical Pharmacology & Therapeutics, has established CPT: Pharmacometrics & Systems Pharmacology to inform the field and shape the discipline.

Data Safe Havens and Trust: Toward a Common Understanding of Trusted Research Platforms for Governing Secure and Ethical Health Research

PubMed Central

Nicholls, Jacqueline; Dobbs, Christine; Sethi, Nayha; Cunningham, James; Ainsworth, John; Heaven, Martin; Peacock, Trevor; Peacock, Anthony; Jones, Kerina; Laurie, Graeme; Kalra, Dipak

2016-01-01

In parallel with the advances in big data-driven clinical research, the data safe haven concept has evolved over the last decade. It has led to the development of a framework to support the secure handling of health care information used for clinical research that balances compliance with legal and regulatory controls and ethical requirements while engaging with the public as a partner in its governance. We describe the evolution of 4 separately developed clinical research platforms into services throughout the United Kingdom-wide Farr Institute and their common deployment features in practice. The Farr Institute is a case study from which we propose a common definition of data safe havens as trusted platforms for clinical academic research. We use this common definition to discuss the challenges and dilemmas faced by the clinical academic research community, to help promote a consistent understanding of them and how they might best be handled in practice. We conclude by questioning whether the common definition represents a safe and trustworthy model for conducting clinical research that can stand the test of time and ongoing technical advances while paying heed to evolving public and professional concerns. PMID:27329087

Advanced practice nurses core competencies: a framework for developing and testing an advanced practice nurse discharge intervention.

PubMed

Cooke, Liz; Gemmill, Robin; Grant, Marcia

2008-01-01

The purpose of this paper was to describe evidenced-based interventions as implemented by advanced practice nurses (APNs) conducting intervention research with a vulnerable population of blood and marrow transplant patients. In addition, each of the 6 core competencies of the APN role identified by Hamric are outlined and applied using a patient case study. These competencies are the following: direct clinical practice, expert coaching and advice, consultation, research skills, clinical and professional leadership, collaboration, and ethical decision making. This article chronicles a typical patient's journey through a post-hospital discharge nursing research study involving APNs as "intervention nurses" and discusses the various aspects of the APN core competencies throughout the process.

Opportunities for Cancer-relevant Innovative Technologies with Transformative Potential | Office of Cancer Clinical Proteomics Research

Cancer.gov

The National Cancer Institute (NCI) is seeking input from the community on identifying priorities with regards to supporting innovative technology development for cancer-relevant research. While the NCI provides support for technology development through a variety of mechanisms, it is important to understand whether or not these are sufficient for catalyzing and supporting the development of tools with significant potential for advancing important fields of cancer research or clinical care.

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

A multimedia perioperative record keeper for clinical research.

PubMed

Perrino, A C; Luther, M A; Phillips, D B; Levin, F L

1996-05-01

To develop a multimedia perioperative recordkeeper that provides: 1. synchronous, real-time acquisition of multimedia data, 2. on-line access to the patient's chart data, and 3. advanced data analysis capabilities through integrated, multimedia database and analysis applications. To minimize cost and development time, the system design utilized industry standard hardware components and graphical. software development tools. The system was configured to use a Pentium PC complemented with a variety of hardware interfaces to external data sources. These sources included physiologic monitors with data in digital, analog, video, and audio as well as paper-based formats. The development process was guided by trials in over 80 clinical cases and by the critiques from numerous users. As a result of this process, a suite of custom software applications were created to meet the design goals. The Perioperative Data Acquisition application manages data collection from a variety of physiological monitors. The Charter application provides for rapid creation of an electronic medical record from the patient's paper-based chart and investigator's notes. The Multimedia Medical Database application provides a relational database for the organization and management of multimedia data. The Triscreen application provides an integrated data analysis environment with simultaneous, full-motion data display. With recent technological advances in PC power, data acquisition hardware, and software development tools, the clinical researcher now has the ability to collect and examine a more complete perioperative record. It is hoped that the description of the MPR and its development process will assist and encourage others to advance these tools for perioperative research.

Implementation of a professional portfolio: a tool to demonstrate professional development for advanced practice.

PubMed

Chamblee, Tracy B; Dale, Juanita Conkin; Drews, Barbie; Spahis, Joanna; Hardin, Teri

2015-01-01

The literature has a gap related to professional development for APRNs. In the United States, many health care organizations use clinical advancement programs for registered nurses, but APRNs are not often included in these programs. If APRNs are included, advancement opportunities are very limited. At CMC, implementation of a professional portfolio resulted in increased satisfaction among APPs regarding their ability to showcase professional growth and expertise, as well as the uniqueness of their advanced practice. Use of the professional portfolio led to improved recognition by APS and organizational leaders of APP performance excellence during the annual performance evaluation, as well as improved recognition among APP colleagues in terms of nominations for honors and awards.

Assessment of competence to complete advance directives: validation of a patient centred approach

PubMed Central

Fazel, Seena; Hope, Tony; Jacoby, Robin

1999-01-01

Objective To develop a patient centred approach for the assessment of competence to complete advance directives (“living wills”) of elderly people with cognitive impairment. Design Semistructured interviews. Setting Oxfordshire. Subjects 50 elderly volunteers living in the community, and 50 patients with dementia on first referral from primary care. Main outcome measures Psychometric properties of competence assessment. Results This patient centred approach for assessing competence to complete advance directives can discriminate between elderly persons living in the community and elderly patients with dementia. The procedure has good interrater (r=0.95) and test-retest (r=0.97) reliability. Validity was examined by relating this approach with a global assessment of competence to complete an advance directive made by two of us (both specialising in old age psychiatry). The data were also used to determine the best threshold score for discriminating between those competent and those incompetent to complete an advance directive. Conclusion A patient centred approach to assess competence to complete advance directives can be reliably and validly used in routine clinical practice. Key messagesAdvance directives could potentially be useful for patients with dementia as a means of extending their autonomy when they become incompetentCompetence to complete an advance directive involves understanding possible future clinical situationsVignettes presenting hypothetical medical problems were tested in 100 elderly people, and were found to validly and reliably discriminate between volunteers living in the community and patients with dementiaWe suggest that two clinical vignettes, each followed by a semistructured interview comprising 10 points, can aid in the assessment of competence to complete advance directives PMID:10024254

Recent Advances in Tissue Engineering Strategies for the Treatment of Joint Damage.

PubMed

Stephenson, Makeda K; Farris, Ashley L; Grayson, Warren L

2017-08-01

While the clinical potential of tissue engineering for treating joint damage has yet to be realized, research and commercialization efforts in the field are geared towards overcoming major obstacles to clinical translation, as well as towards achieving engineered grafts that recapitulate the unique structures, function, and physiology of the joint. In this review, we describe recent advances in technologies aimed at obtaining biomaterials, stem cells, and bioreactors that will enable the development of effective tissue-engineered treatments for repairing joint damage. 3D printing of scaffolds is aimed at improving the mechanical structure and microenvironment necessary for bone regeneration within a damaged joint. Advances in our understanding of stem cell biology and cell manufacturing processes are informing translational strategies for the therapeutic use of allogeneic and autologous cells. Finally, bioreactors used in combination with cells and biomaterials are promising strategies for generating large tissue grafts for repairing damaged tissues in pre-clinical models. Together, these advances along with ongoing research directions are making tissue engineering increasingly viable for the treatment of joint damage.

Barriers and enablers to advanced practitioners' ability to enact their leadership role: A scoping review.

PubMed

Elliott, Naomi; Begley, Cecily; Sheaf, Greg; Higgins, Agnes

2016-08-01

Advanced roles such as nurse practitioner, nurse consultant and advanced nurse or midwife practitioner are increasing across the world. In most countries, clinical practice, education, leadership and research are the four components that define the advanced practitioner's role. Of these, leadership is perhaps the most important part of the role, but its study has largely been neglected. There is a risk that failure to identify and respond to barriers to enacting the advanced practitioners' leadership role will limit the extent to which they can become strategic leaders for professional development, and jeopardise the long-term sustainability of the role. To identify the barriers and enablers to advanced practitioner's ability to enact their leadership role. A search of the research literature was undertaken in electronic databases (PubMed, CINAHL, PsycINFO, ProQuest Dissertation and Theses, from inception to 4-6th June 2015), unpublished research in seventeen online research repositories and institutes, and hand search of 2 leadership journals (March/April 2010-4th June 2015). Using pre-set inclusion criteria, the 1506 titles found were screened by two authors working independently. The 140 full text reports selected were reviewed by two authors separately and 34 were included, and data extracted and cross-checked. Any disagreements were discussed by the scoping team until consensus was reached. Using content analysis, the barriers and enablers relating to leadership enactment were sorted into themes based on their common characteristics, and using a Structure-Process-Outcome conceptual framework were categorised under the four structural layers: (1) healthcare system-level, (2) organisational-level, (3) team-level, and (4) advanced practitioner-level. Thirteen barriers to, and 11 enablers of, leadership were identified. Of these a majority (n=14) were related to organisational-level factors such as mentoring, support from senior management, opportunity to participate at strategic level, structural supports for the role, and size of clinical caseload. Advanced practitioner-level factors relating to personal attributes, knowledge, skills and values of the advanced practitioner were identified. Although building leadership capabilities at advanced practitioner-level and team-level are important, without key inputs from healthcare managers, advanced practitioners' leadership enactment will remain at the level of clinical practice, and their contribution as change agents and innovators at the strategic level of service development and development of the nursing profession will be not be realised. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of other microtubule-stabilizer families: the epothilones and their derivatives.

PubMed

Brogdon, Cynthia F; Lee, Francis Y; Canetta, Renzo M

2014-05-01

Chemotherapy is the mainstay of treatment for numerous cancer types, but resistance to chemotherapy remains a major clinical issue and is one of the driving influences underlying the development of new anticancer medications. One of the most important classes of chemotherapy agents is the taxanes, which target the cytoskeleton and spindle apparatus of tumor cells by binding to the microtubules, thereby disrupting key cellular mechanisms, including mitosis. Taxane resistance, however, limits treatment options and creates a major challenge for clinicians. Ongoing research has identified several newer classes of microtubule-targeting chemotherapies that may retain activity despite clinical resistance to taxanes. Among these classes, the epothilones have been studied most extensively in the clinical setting. Like taxanes, epothilones stabilize microtubulin turnover, and they have properties favoring their development as anticancer agents. The most clinically advanced epothilone analog is ixabepilone, which is currently the only approved epothilone derivative. Ixabepilone is indicated for the treatment of metastatic or locally advanced breast cancer in combination with capecitabine after failure of an anthracycline and a taxane, or as monotherapy after failure of an anthracycline, a taxane, and capecitabine. In phase II and III trials, ixabepilone showed efficacy in several patient subgroups and in various stages of breast cancer. Common adverse reactions include peripheral sensory neuropathy and asthenia. This paper will discuss the preclinical and clinical development of epothilones and their derivatives across a variety of cancer types.

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 use of transgenic parasites in malaria vaccine research.

PubMed

Othman, Ahmad Syibli; Marin-Mogollon, Catherin; Salman, Ahmed M; Franke-Fayard, Blandine M; Janse, Chris J; Khan, Shahid M

2017-07-01

Transgenic malaria parasites expressing foreign genes, for example fluorescent and luminescent proteins, are used extensively to interrogate parasite biology and host-parasite interactions associated with malaria pathology. Increasingly transgenic parasites are also exploited to advance malaria vaccine development. Areas covered: We review how transgenic malaria parasites are used, in vitro and in vivo, to determine protective efficacy of different antigens and vaccination strategies and to determine immunological correlates of protection. We describe how chimeric rodent parasites expressing P. falciparum or P. vivax antigens are being used to directly evaluate and rank order human malaria vaccines before their advancement to clinical testing. In addition, we describe how transgenic human and rodent parasites are used to develop and evaluate live (genetically) attenuated vaccines. Expert commentary: Transgenic rodent and human malaria parasites are being used to both identify vaccine candidate antigens and to evaluate both sub-unit and whole organism vaccines before they are advanced into clinical testing. Transgenic parasites combined with in vivo pre-clinical testing models (e.g. mice) are used to evaluate vaccine safety, potency and the durability of protection as well as to uncover critical protective immune responses and to refine vaccination strategies.

Advances in sarcoma diagnostics and treatment

PubMed Central

Dancsok, Amanda R; Asleh-Aburaya, Karama; Nielsen, Torsten O

2017-01-01

The heterogeneity of sarcomas with regard to molecular genesis, histology, clinical characteristics, and response to treatment makes management of these rare yet diverse neoplasms particularly challenging. This review encompasses recent developments in sarcoma diagnostics and treatment, including cytotoxic, targeted, epigenetic, and immune therapy agents. In the past year, groups internationally explored the impact of adding mandatory molecular testing to histological diagnosis, reporting some changes in diagnosis and/or management; however, the impact on outcomes could not be adequately assessed. Transcriptome sequencing techniques have brought forward new diagnostic tools for identifying fusions and/or characterizing unclassified entities. Next-generation sequencing and advanced molecular techniques were also applied to identify potential targets for directed and epigenetic therapy, where preclinical studies reported results for agents active within the receptor tyrosine kinase, mTOR, Notch, Wnt, Hedgehog, Hsp90, and MDM2 signaling networks. At the level of clinical practice, modest developments were seen for some sarcoma subtypes in conventional chemotherapy and in therapies targeting the pathways activated by various receptor tyrosine kinases. In the burgeoning field of immune therapy, sarcoma work is in its infancy; however, elaborate protocols for immune stimulation are being explored, and checkpoint blockade agents advance from preclinical models to clinical studies. PMID:27732970

Diagnosis of Periodontal Diseases: Building a Bridge from Today's Methods to Tomorrow's Technology.

ERIC Educational Resources Information Center

Jeffcoat, Marjorie K.

1994-01-01

A discussion of advancements in diagnosis of periodontal diseases looks first at the screening process, reviews specific periodontal diseases and their clinical signs and symptoms, and explains both traditional and newly developed diagnostic tests. A framework for understanding the tests' clinical usefulness is also presented. (MSE)

Childhood Developmental Disorders: An Academic and Clinical Convergence Point for Psychiatry, Neurology, Psychology and Pediatrics

ERIC Educational Resources Information Center

Reiss, Allan L.

2009-01-01

Background: Significant advances in understanding brain development and behavior have not been accompanied by revisions of traditional academic structure. Disciplinary isolation and a lack of meaningful interdisciplinary opportunities are persistent barriers in academic medicine. To enhance clinical practice, research, and training for the next…

Developing Clinically Practicable Biomarkers for Autism Spectrum Disorder

ERIC Educational Resources Information Center

McPartland, James C.

2017-01-01

Despite significant advances in understanding the biological bases of autism spectrum disorder (ASD), the field remains primarily reliant on observational and parent report measures of behavior to guide clinical practice, conduct research, and evaluate intervention outcomes. There is a critical need for objective measures to more sensitively and…

Emerging Research and Clinical Development Trends of Liposome and Lipid Nanoparticle Drug Delivery Systems

PubMed Central

KRAFT, JOHN C.; FREELING, JENNIFER P.; WANG, ZIYAO; HO, RODNEY J. Y.

2014-01-01

Liposomes are spherical-enclosed membrane vesicles mainly constructed with lipids. Lipid nanoparticles are loaded with therapeutics and may not contain an enclosed bilayer. The majority of those clinically approved have diameters of 50–300 nm. The growing interest in nanomedicine has fueled lipid–drug and lipid–protein studies, which provide a foundation for developing lipid particles that improve drug potency and reduce off-target effects. Integrating advances in lipid membrane research has enabled therapeutic development. At present, about 600 clinical trials involve lipid particle drug delivery systems. Greater understanding of pharmacokinetics, biodistribution, and disposition of lipid–drug particles facilitated particle surface hydration technology (with polyethylene glycol) to reduce rapid clearance and provide sufficient blood circulation time for drug to reach target tissues and cells. Surface hydration enabled the liposome-encapsulated cancer drug doxorubicin (Doxil) to gain clinical approval in 1995. Fifteen lipidic therapeutics are now clinically approved. Although much research involves attaching lipid particles to ligands selective for occult cells and tissues, preparation procedures are often complex and pose scale-up challenges. With emerging knowledge in drug target and lipid–drug distribution in the body, a systems approach that integrates knowledge to design and scale lipid–drug particles may further advance translation of these systems to improve therapeutic safety and efficacy. PMID:24338748

The clinical applications of genome editing in HIV.

PubMed

Wang, Cathy X; Cannon, Paula M

2016-05-26

HIV/AIDS has long been at the forefront of the development of gene- and cell-based therapies. Although conventional gene therapy approaches typically involve the addition of anti-HIV genes to cells using semirandomly integrating viral vectors, newer genome editing technologies based on engineered nucleases are now allowing more precise genetic manipulations. The possible outcomes of genome editing include gene disruption, which has been most notably applied to the CCR5 coreceptor gene, or the introduction of small mutations or larger whole gene cassette insertions at a targeted locus. Disruption of CCR5 using zinc finger nucleases was the first-in-human application of genome editing and remains the most clinically advanced platform, with 7 completed or ongoing clinical trials in T cells and hematopoietic stem/progenitor cells (HSPCs). Here we review the laboratory and clinical findings of CCR5 editing in T cells and HSPCs for HIV therapy and summarize other promising genome editing approaches for future clinical development. In particular, recent advances in the delivery of genome editing reagents and the demonstration of highly efficient homology-directed editing in both T cells and HSPCs are expected to spur the development of even more sophisticated applications of this technology for HIV therapy. © 2016 by The American Society of Hematology.

Framework for development of physician competencies in genomic medicine: report of the Competencies Working Group of the Inter-Society Coordinating Committee for Physician Education in Genomics.

PubMed

Korf, Bruce R; Berry, Anna B; Limson, Melvin; Marian, Ali J; Murray, Michael F; O'Rourke, P Pearl; Passamani, Eugene R; Relling, Mary V; Tooker, John; Tsongalis, Gregory J; Rodriguez, Laura L

2014-11-01

Completion of the Human Genome Project, in conjunction with dramatic reductions in the cost of DNA sequencing and advances in translational research, is gradually ushering genomic discoveries and technologies into the practice of medicine. The rapid pace of these advances is opening up a gap between the knowledge available about the clinical relevance of genomic information and the ability of clinicians to include such information in their medical practices. This educational gap threatens to be rate limiting to the clinical adoption of genomics in medicine. Solutions will require not only a better understanding of the clinical implications of genetic discoveries but also training in genomics at all levels of professional development, including for individuals in formal training and others who long ago completed such training. The National Human Genome Research Institute has convened the Inter-Society Coordinating Committee for Physician Education in Genomics (ISCC) to develop and share best practices in the use of genomics in medicine. The ISCC has developed a framework for development of genomics practice competencies that may serve as a starting point for formulation of competencies for physicians in various medical disciplines.

Advancement of the Artificial Pancreas through the Development of Interoperability Standards

PubMed Central

Picton, Peter E.; Yeung, Melanie; Hamming, Nathaniel; Desborough, Lane; Dassau, Eyal; Cafazzo, Joseph A.

2013-01-01

Despite advancements in the development of the artificial pancreas, barriers in the form of proprietary data and communication protocols of diabetes devices have made the integration of these components challenging. The Artificial Pancreas Standards and Technical Platform Project is an initiative funded by the JDRF Canadian Clinical Trial Network with the goal of developing device communication standards for the interoperability of diabetes devices. Stakeholders from academia, industry, regulatory agencies, and medical and patient communities have been engaged in advancing this effort. In this article, we describe this initiative along with the process involved in working with the standards organizations and stakeholders that are key to ensuring effective standards are developed and adopted. Discussion from a special session of the 12th Annual Diabetes Technology Meeting is also provided. PMID:23911190

The ADVANCE network: accelerating data value across a national community health center network

PubMed Central

DeVoe, Jennifer E; Gold, Rachel; Cottrell, Erika; Bauer, Vance; Brickman, Andrew; Puro, Jon; Nelson, Christine; Mayer, Kenneth H; Sears, Abigail; Burdick, Tim; Merrell, Jonathan; Matthews, Paul; Fields, Scott

2014-01-01

The ADVANCE (Accelerating Data Value Across a National Community Health Center Network) clinical data research network (CDRN) is led by the OCHIN Community Health Information Network in partnership with Health Choice Network and Fenway Health. The ADVANCE CDRN will ‘horizontally’ integrate outpatient electronic health record data for over one million federally qualified health center patients, and ‘vertically’ integrate hospital, health plan, and community data for these patients, often under-represented in research studies. Patient investigators, community investigators, and academic investigators with diverse expertise will work together to meet project goals related to data integration, patient engagement and recruitment, and the development of streamlined regulatory policies. By enhancing the data and research infrastructure of participating organizations, the ADVANCE CDRN will serve as a ‘community laboratory’ for including disadvantaged and vulnerable patients in patient-centered outcomes research that is aligned with the priorities of patients, clinics, and communities in our network. PMID:24821740

Discovering the nature of advanced nursing practice in high dependency care: a critical care nurse consultant's experience.

PubMed

Fairley, Debra

2005-06-01

This paper describes how a critical care nurse consultant's clinical role has evolved within a surgical high dependency unit (SHDU) in a large teaching hospitals trust. In order to provide some background to role development, an overview of the research exploring the nature of advanced nursing practice in the context of critical care will be presented. From the outset, advanced nursing practice was not perceived as the acquisition and application of technical procedures usually undertaken by doctors, but possibly an integration of medicine and nursing where holistic nursing assessment is combined with symptom-focused physical examination. A reflective account of practical problems encountered relating to role integration, professional autonomy, legal and consent issues, non-medical prescribing, and role evaluation will be presented. A model of working that can be applied to high dependency units, integrating the role of the advanced nurse practitioner within the clinical team, will be described.

Adaptation through Collaboration: Developing Novel Platforms to Advance the Delivery of Advanced Therapies to Patients

PubMed Central

Papadaki, Magdalini

2017-01-01

For the nascent field of advanced therapies, collaboration will be a game-changer, turning scientific progress that was once unimaginable into transformative medical practice. Despite promise for lifelong management and even cure of disease, skepticism remains about the feasibility of their delivery to patients, fueling investment risks. With the potential for long-term effectiveness in need of frequent reassessment, current approaches to predict real-life drug performance bear little relevance, necessitating novel and iterative schemes to monitoring the benefit–risk profiles throughout the life span of advanced therapies. This work explains that reinventing an adoption route for Advanced Therapy Medicinal Products is as much about the scientific and clinical components, as it is about the organizational structures, requiring an unprecedented level of interactions between stakeholders not traditionally connected; from developers and regulators, to payers, patients, and funders. By reflecting on the successes and lessons learned from the growing space of global precompetitive consortia and public–private partnerships, as well as a number of emerging accelerated development pathways, this work aims to inform the foundations for a future roadmap that can smooth the path to approval, reimbursement, and access, while delivering value to all stakeholders. Echoing the growing demands to bring these transformative products to patients, it provides critical insights to enhance our capacity in three fundamental domains: deploying the operational flexibilities offered by the growing space of collaborations, utilizing emerging flexible and accelerated pathways to tackle challenges in quantifying long-term effectiveness, and building the necessary digital and clinical infrastructure for knowledge development. PMID:28611985

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.

[Newly Designed Water Treatment Systems for Hospital Effluent].

PubMed

Azuma, Takashi

2018-01-01

　Pharmaceuticals are indispensable to contemporary life. Recently, the emerging problem of pharmaceutical-based pollution of river environments, including drinking water sources and lakes, has begun to receive significant attention worldwide. Because pharmaceuticals are designed to perform specific physiological functions in targeted regions of the human body, there is increasing concern regarding their toxic effects, even at low concentrations, on aquatic ecosystems and human health, via residues in drinking water. Pharmaceuticals are consistently employed in hospitals to treat disease; and Japan, one of the most advanced countries in medical treatment, ranks second worldwide in the quantity of pharmaceuticals employed. Therefore, the development of technologies that minimize or lessen the related environmental risks for clinical effluent is an important task as well as that for sewage treatment plants (STPs). However, there has been limited research on clinical effluent, and much remains to be elucidated. In light of this, we are investigating the occurrence of pharmaceuticals, and the development of water treatment systems for clinical effluent. This review discusses the current research on clinical effluent and the development of advanced water treatment systems targeted at hospital effluent, and explores strategies for future environmental risk assessment and risk management.

Recent advances in bioelectric prostheses

PubMed Central

Pasquina, Paul F.; Perry, Briana N.; Miller, Matthew E.; Ling, Geoffrey S.F.; Tsao, Jack W.

2015-01-01

Summary Worldwide prevalence of amputation has created an increasing demand for improved upper and lower extremity prostheses. Current prosthetics are often uncomfortable and difficult to control and provide limited functional restoration. Moreover, the inability to normalize anthropomorphic biomechanics with a prosthesis increases one's risk of developing long-term health risks such as arthritis, skin breakdown, and pain. Recent advances in bionic prosthetic development hold great promise for rehabilitation and improving quality of life with limb loss. This brief review discusses the current state of advanced prostheses, the integration of robotics in the care of individuals with major limb amputation, and some innovative surgical techniques that are being explored for clinical feasibility. PMID:29443190

Drug development and nonclinical to clinical translational databases: past and current efforts.

PubMed

Monticello, Thomas M

2015-01-01

The International Consortium for Innovation and Quality (IQ) in Pharmaceutical Development is a science-focused organization of pharmaceutical and biotechnology companies. The mission of the Preclinical Safety Leadership Group (DruSafe) of the IQ is to advance science-based standards for nonclinical development of pharmaceutical products and to promote high-quality and effective nonclinical safety testing that can enable human risk assessment. DruSafe is creating an industry-wide database to determine the accuracy with which the interpretation of nonclinical safety assessments in animal models correctly predicts human risk in the early clinical development of biopharmaceuticals. This initiative aligns with the 2011 Food and Drug Administration strategic plan to advance regulatory science and modernize toxicology to enhance product safety. Although similar in concept to the initial industry-wide concordance data set conducted by International Life Sciences Institute's Health and Environmental Sciences Institute (HESI/ILSI), the DruSafe database will proactively track concordance, include exposure data and large and small molecules, and will continue to expand with longer duration nonclinical and clinical study comparisons. The output from this work will help identify actual human and animal adverse event data to define both the reliability and the potential limitations of nonclinical data and testing paradigms in predicting human safety in phase 1 clinical trials. © 2014 by The Author(s).

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

Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update

PubMed Central

Miele, Lucio; Harris, Pamela Jo; Jeong, Woondong; Bando, Hideaki; Kahn, Michael; Yang, Sherry X.

2015-01-01

During the past decade, cancer stem cells (CSCs) have been increasingly identified in many malignancies. Although the origin and plasticity of these cells remain controversial, tumour heterogeneity and the presence of small populations of cells with stem-like characteristics is established in most malignancies. CSCs display many features of embryonic or tissue stem cells, and typically demonstrate persistent activation of one or more highly conserved signal transduction pathways involved in development and tissue homeostasis, including the Notch, Hedgehog (HH), and Wnt pathways. CSCs generally have slow growth rates and are resistant to chemotherapy and/or radiotherapy. Thus, new treatment strategies targeting these pathways to control stem-cell replication, survival and differentiation are under development. Herein, we provide an update on the latest advances in the clinical development of such approaches, and discuss strategies for overcoming CSC-associated primary or acquired resistance to cancer treatment. Given the crosstalk between the different embryonic developmental signalling pathways, as well as other pathways, designing clinical trials that target CSCs with rational combinations of agents to inhibit possible compensatory escape mechanisms could be of particular importance. We also share our views on the future directions for targeting CSCs to advance the clinical development of these classes of agents. PMID:25850553

Bazedoxifene exhibits antiestrogenic activity in animal models of tamoxifen-resistant breast cancer: implications for treatment of advanced disease.

PubMed

Wardell, Suzanne E; Nelson, Erik R; Chao, Christina A; McDonnell, Donald P

2013-05-01

There is compelling evidence to suggest that drugs that function as pure estrogen receptor (ER-α) antagonists, or that downregulate the expression of ER-α, would have clinical use in the treatment of advanced tamoxifen- and aromatase-resistant breast cancer. Although such compounds are currently in development, we reasoned, based on our understanding of ER-α pharmacology, that there may already exist among the most recently developed selective estrogen receptor modulators (SERM) compounds that would have usage as breast cancer therapeutics. Thus, our objective was to identify among available SERMs those with unique pharmacologic activities and to evaluate their potential clinical use with predictive models of advanced breast cancer. A validated molecular profiling technology was used to classify clinically relevant SERMs based on their impact on ER-α conformation. The functional consequences of these observed mechanistic differences on (i) gene expression, (ii) receptor stability, and (iii) activity in cellular and animal models of advanced endocrine-resistant breast cancer were assessed. The high-affinity SERM bazedoxifene was shown to function as a pure ER-α antagonist in cellular models of breast cancer and effectively inhibited the growth of both tamoxifen-sensitive and -resistant breast tumor xenografts. Interestingly, bazedoxifene induced a unique conformational change in ER-α that resulted in its proteasomal degradation, although the latter activity was dispensable for its antagonist efficacy. Bazedoxifene was recently approved for use in the European Union for the treatment of osteoporosis and thus may represent a near-term therapeutic option for patients with advanced breast cancer. ©2013 AACR.

Clopidogrel and warfarin pharmacogenetic tests: what is the evidence for use in clinical practice?

PubMed Central

Shahin, Mohamed H.A.; Johnson, Julie A.

2013-01-01

Purpose of review To review the most promising genetic markers associated with the variability in the safety or efficacy of warfarin and clopidogrel and highlight the verification and validation initiatives for translating clopidogrel and warfarin pharmacogenetic tests to clinical practice. Recent findings Rapid advances in pharmacogenetics, continuous decrease in genotyping cost, development of point-of-care devices and the newly established clinical genotyping programs at several institutions hold the promise of individualizing clopidogrel and warfarin based on genotype. Guidelines have been established to assist clinicians in prescribing clopidogrel or warfarin dose based on genotype. However, the clinical utility of clopidogrel and warfarin is still limited. Accordingly, large randomized clinical trials are underway to define the role of clopidogrel and warfarin pharmacogenetics in clinical practice. Summary Pharmacogenetics has offered compelling evidence toward the individualization of clopidogrel and warfarin therapies. The rapid advances in technology make the clinical implementation of clopidogrel and warfarin pharmacogenetics possible. The clinical genotyping programs and the ongoing clinical trials will help in overcoming some of the barriers facing the clinical implementation of clopidogrel and warfarin pharmacogenetics. PMID:23478884

The Development, Commercialization, and Impact of Optical Coherence Tomography.

PubMed

Fujimoto, James; Swanson, Eric

2016-07-01

This review was written for the special issue of IOVS to describe the history of optical coherence tomography (OCT) and its evolution from a nonscientific, historic perspective. Optical coherence tomography has become a standard of care in ophthalmology, providing real-time information on structure and function - diagnosing disease, evaluating progression, and assessing response to therapy, as well as helping to understand disease pathogenesis and create new therapies. Optical coherence tomography also has applications in multiple clinical specialties, fundamental research, and manufacturing. We review the early history of OCT describing how research and development evolves and the important role of multidisciplinary collaboration and expertise. Optical coherence tomography had its origin in femtosecond optics, but used optical communications technologies and required advanced engineering for early OCT prototypes, clinical feasibility studies, entrepreneurship, and corporate development in order to achieve clinical acceptance and clinical impact. Critical advances were made by early career researchers, clinician scientists, engineering experts, and business leaders, which enabled OCT to have a worldwide impact on health care. We introduce the concept of an "ecosystem" consisting of research, government funding, collaboration and competition, clinical studies, innovation, entrepreneurship and industry, and impact - all of which must work synergistically. The process that we recount is long and challenging, but it is our hope that it might inspire early career professionals in science, engineering, and medicine, and that the clinical and research community will find this review of interest.

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

PubMed

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

2015-01-01

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

Advance Care Planning Documentation in Electronic Health Records: Current Challenges and Recommendations for Change.

PubMed

Lamas, Daniela; Panariello, Natalie; Henrich, Natalie; Hammes, Bernard; Hanson, Laura C; Meier, Diane E; Guinn, Nancy; Corrigan, Janet; Hubber, Sean; Luetke-Stahlman, Hannah; Block, Susan

2018-04-01

To develop a set of clinically relevant recommendations to improve the state of advance care planning (ACP) documentation in the electronic health record (EHR). Advance care planning (ACP) is a key process that supports goal-concordant care. For preferences to be honored, clinicians must be able to reliably record, find, and use ACP documentation. However, there are no standards to guide ACP documentation in the electronic health record (EHR). We interviewed 21 key informants to understand the strengths and weaknesses of EHR documentation systems for ACP and identify best practices. We analyzed these interviews using a qualitative content analysis approach and subsequently developed a preliminary set of recommendations. These recommendations were vetted and refined in a second round of input from a national panel of content experts. Informants identified six themes regarding current inadequacies in documentation and accessibility of ACP information and opportunities for improvement. We offer a set of concise, clinically relevant recommendations, informed by expert opinion, to improve the state of ACP documentation in the EHR.

Targeting cancer with hyaluronic acid-based nanocarriers: recent advances and translational perspectives.

PubMed

Cadete, Ana; Alonso, María José

2016-09-01

Hyaluronic acid is a natural polysaccharide that has been widely explored for the development of anticancer therapies due to its ability to target cancer cells. Moreover, advances made in the last decade have revealed the versatility of this biomaterial in the design of multifunctional carriers, intended for the delivery of a variety of bioactive molecules, including polynucleotides, immunomodulatory drugs and imaging agents. In this review, we aim to provide an overview of the major recent achievements in this field, highlighting the application of the newly developed nanostructures in combination therapies, immunomodulation and theranostics. Finally, we will discuss the main challenges and technological advances that will allow these carriers to be considered as candidates for clinical development.

Conditionally replicative adenovirus for gastrointestinal cancers.

PubMed

Yamamoto, Masato

2004-08-01

The clinical outcome of advanced gastrointestinal (GI) cancers (especially pancreatic and oesophageal cancers) is dismal, despite the advance of conventional therapeutic strategies. Cancer gene therapy is a category of new therapeutics, among which conditionally replicative adenovirus (CRAd) is one promising strategy to overcome existing obstacles of cancer gene therapy. Various CRAds have been developed for GI cancer treatment by taking advantage of the replication biology of adenovirus. Some CRAds have already been tested in clinical trials, but have fallen short of initial expectations. Concerns for clinical applicability include therapeutic potency, replication selectivity and interval end points in clinical trials. In addition, improvement of experimental animal models is needed for a deeper understanding of CRAd biology. Despite these obstacles, CRAds continue to be an exciting area of investigation with great potential for clinical utility. Further virological and oncological research will eventually lead to full realisation of the therapeutic potential of CRAds in the field of GI cancers.

Predicting adverse hemodynamic events in critically ill patients.

PubMed

Yoon, Joo H; Pinsky, Michael R

2018-06-01

The art of predicting future hemodynamic instability in the critically ill has rapidly become a science with the advent of advanced analytical processed based on computer-driven machine learning techniques. How these methods have progressed beyond severity scoring systems to interface with decision-support is summarized. Data mining of large multidimensional clinical time-series databases using a variety of machine learning tools has led to our ability to identify alert artifact and filter it from bedside alarms, display real-time risk stratification at the bedside to aid in clinical decision-making and predict the subsequent development of cardiorespiratory insufficiency hours before these events occur. This fast evolving filed is primarily limited by linkage of high-quality granular to physiologic rationale across heterogeneous clinical care domains. Using advanced analytic tools to glean knowledge from clinical data streams is rapidly becoming a reality whose clinical impact potential is great.

Recent advances in the molecular genetics of epilepsy.

PubMed

Hildebrand, Michael S; Dahl, Hans-Henrik M; Damiano, John Anthony; Smith, Richard J H; Scheffer, Ingrid E; Berkovic, Samuel F

2013-05-01

Recent advances in molecular genetics have translated into the increasing utilisation of genetic testing in the routine clinical practice of neurologists. There has been a steady, incremental increase in understanding the genetic variation associated with epilepsies. Genetic testing in the epilepsies is not yet widely practiced, but the advent of new screening technologies promises to exponentially expand both knowledge and clinical utility. To maximise the value of this new genetic insight we need to rapidly extrapolate genetic findings to inform patients of their diagnosis, prognosis, recurrence risk and the clinical management options available for their specific genetic condition. Comprehensive, highly specific and sensitive genetic test results improve the management of patients by neurologists and clinical geneticists. Here we discuss the latest developments in clinical genetic testing for epilepsy and describe new molecular genetics platforms that will transform both genetic screening and novel gene discovery.

Wise Additions Bridge the Gap between Social Psychology and Clinical Practice: Cognitive-Behavioral Therapy as an Exemplar

PubMed Central

Folk, Johanna B.; Disabato, David J.; Goodman, Fallon R.; Carter, Sarah P.; DiMauro, Jennifer C.; Riskind, John H.

2017-01-01

Progress in clinical science, theory, and practice requires the integration of advances from multiple fields of psychology, but much integration remains to be done. The current article seeks to address the specific gap that exists between basic social psychological theories and the implementation of related therapeutic techniques. We propose several “wise additions,” based upon the principles outlined by Walton (2014), intended to bridge current social psychological research with clinical psychological therapeutic practice using cognitive behavioral therapy as an example. We consider how recent advances in social psychological theories can inform the development and implementation of wise additions in clinical case conceptualization and interventions. We specifically focus on self and identity, self-affirmation, transference, social identity, and embodied cognition, five dominant areas of interest in the field that have clear clinical applications. PMID:28919701

Preliminary Characterization of the Noise-Immune Stethoscope (NIS) in High Ambient Noise Environment Using a Reverberation Sound Chamber

DTIC Science & Technology

2010-02-01

unlimited This report details the preliminary testing of advanced technology development for clinical auscultation in high noise environments. The Noise...represents a viable answer to the need for clinical auscultation in high noise environments across the spectrum of casualty care. stethoscope, auscultation ...sounds, and these sounds prove very useful for clinical assessment and diagnosis (Bloch, 1993). Since that time, clinical auscultation by way of a

Advanced functional polymers for regenerative and therapeutic dentistry.

PubMed

Lai, W-F; Oka, K; Jung, H-S

2015-07-01

Use of ceramics and polymers continues to dominate clinical procedures in modern dentistry. Polymers have provided the basis for adhesives, tissue void fillers, and artificial replacements for whole teeth. They have been remarkably effective in the clinic at restoration of major dental functions after damage or loss of teeth. With the rapid development of polymer science, dental materials science has significantly lagged behind in harnessing these advanced polymer products. What they offer is new and unique properties superior to traditional polymers and crucially a range of properties that more closely match natural biomaterials. Therefore, we should pursue more vigorously the benefits of advanced polymers in dentistry. In this review, we highlight how the latest generation of advanced polymers will enhance the application of materials in the dental clinic using numerous promising examples. Polymers have a broad range of applications in modern dentistry. Some major applications are to construct frameworks that mimic the precise structure of tissues, to restore tooth organ function, and to deliver bioactive agents to influence cell behavior from the inside. The future of polymers in dentistry must include all these new enhancements to increase biological and clinical effectiveness beyond what can be achieved with traditional biomaterials. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Antiretroviral Therapy in Advanced HIV Disease: Which is the Best Regimen?

PubMed

Burgos, Joaquin; Ribera, Esteban; Falcó, Vicenç

2018-01-01

Advanced HIV disease, defined as a CD4 cell count below 200 cells/μl or the presence of an AIDS-defining illness, remains common among HIV-infected individuals who first present for medical care. In developed countries, nearly 30% of new HIV diagnoses occurred at advanced stages of the disease, and it is important because advanced HIV disease has been associated with worse clinical outcomes, including lower rates of virological response, higher morbidity, and higher mortality. However, there are scarce data regarding which is the best antiretroviral regimen in these patients. Nowadays, integrase inhibitor-based regimens are widely recommended as the best initial therapy for treatment-naïve HIV-infected patients by all international guidelines. However, these guidelines hardly mention the recommended regimens in individuals with advanced HIV disease. Otherwise, recent data indicating a higher risk of immune reconstitution inflammatory syndrome associated to the use of integrase inhibitors have raised concerns on the use of these drugs in patients with advanced HIV disease. The aim of this article is to review the available evidence from randomized clinical trials for the best treatment in patients with advanced HIV disease.

Advancing molecular-guided surgery through probe development and testing in a moderate cost evaluation pipeline

NASA Astrophysics Data System (ADS)

Pogue, Brian W.; Paulsen, Keith D.; Hull, Sally M.; Samkoe, Kimberley S.; Gunn, Jason; Hoopes, Jack; Roberts, David W.; Strong, Theresa V.; Draney, Daniel; Feldwisch, Joachim

2015-03-01

Molecular guided oncology surgery has the potential to transform the way decisions about resection are done, and can be critically important in areas such as neurosurgery where the margins of tumor relative to critical normal tissues are not readily apparent from visual or palpable guidance. Yet there are major financial barriers to advancing agents into clinical trials with commercial backing. We observe that development of these agents in the standard biological therapeutic paradigm is not viable, due to the high up front financial investment needed and the limitations in the revenue models of contrast agents for imaging. The hypothesized solution to this problem is to develop small molecular biologicals tagged with an established fluorescent reporter, through the chemical agent approval pathway, targeting a phase 0 trials initially, such that the initial startup phase can be completely funded by a single NIH grant. In this way, fast trials can be completed to de-risk the development pipeline, and advance the idea of fluorescence-guided surgery (FGS) reporters into human testing. As with biological therapies the potential successes of each agent are still moderate, but this process will allow the field to advance in a more stable and productive manner, rather than relying upon isolated molecules developed at high cost and risk. The pathway proposed and tested here uses peptide synthesis of an epidermal growth factor receptor (EGFR)-binding Affibody molecules, uniquely conjugated to IRDye 800CW, developed and tested in academic and industrial laboratories with well-established records for GMP production, fill and finish, toxicity testing, and early phase clinical trials with image guidance.

A focus group study of the use of video-recorded simulated objective structured clinical examinations in nurse practitioner education.

PubMed

Barratt, Julian

2010-05-01

The objective structured clinical examination (OSCE) is a common method of clinical skills assessment used for advanced nurse practitioner students across the United Kingdom. The purpose of an advanced nursing OSCE is to assess a nurse practitioner student's competence and safety in the performance of commonly used advanced clinical practice skills. Students often feel nervous when preparing for and participating in an OSCE. Consideration of these identified anxieties led to the development of an alternative method of meeting students' OSCE learning and preparation needs; namely video-recorded simulated OSCEs. Video-recording was appealing for the following reasons: it provides a flexible usage of staff resources and time; OSCE performance mistakes can be rectified; it is possible to use the same video-recordings with multiple cohorts of students, and the recordings can be made conveniently available for students with video streaming on internet-based video-sharing sites or virtual learning environments. The aim of the study was to explore the value of using such recordings amongst nurse practitioner students, via online and face-to-face focus groups, to see if they are a suitable OSCE educational preparation technique. The study findings indicate that simulated OSCE video-recordings are an effective method for supporting nurse practitioner educational development. Copyright 2009 Elsevier Ltd. All rights reserved.

Driving CT developments the last mile: case examples of successful and somewhat less successful translations into clinical practice

NASA Astrophysics Data System (ADS)

Sodickson, Aaron D.

2017-03-01

CT technology has advanced rapidly in recent years, yet not all innovations translate readily into clinical practice. Technology advances must meet certain key requirements to make it into routine use: They must provide a well-defined clinical benefit. They must be easy to use and integrate readily into existing workflows, or better still, further streamline these workflows. These requirements heavily favor fully integrated or automated solutions that remove the human factor and provide a reproducible output independent of operator skill level. Further, to achieve these aims, collaboration with the ultimate end users is needed as early as possible in the development cycle, not just at the point of product testing. Technology innovators are encouraged to engage such collaborators even at early stages of feature or product definition. This manuscript highlights these concepts through exploration of challenging areas in CT imaging in an Emergency Department setting. Technique optimization for pulmonary embolus CT is described as an example of successful integration of multiple advances in radiation dose reduction and imaging speed. The typical workflow of a trauma "pan-scan" (incorporating scans from head through pelvis) is described to highlight workflow challenges and opportunities for improvement. Finally, Dual Energy CT is discussed to highlight the undeniable clinical value of the material characterization it provides, yet also its surprisingly slow integration into routine use beyond early adopters.

Current State of Animal (Mouse) Modeling in Melanoma Research.

PubMed

Kuzu, Omer F; Nguyen, Felix D; Noory, Mohammad A; Sharma, Arati

2015-01-01

Despite the considerable progress in understanding the biology of human cancer and technological advancement in drug discovery, treatment failure remains an inevitable outcome for most cancer patients with advanced diseases, including melanoma. Despite FDA-approved BRAF-targeted therapies for advanced stage melanoma showed a great deal of promise, development of rapid resistance limits the success. Hence, the overall success rate of melanoma therapy still remains to be one of the worst compared to other malignancies. Advancement of next-generation sequencing technology allowed better identification of alterations that trigger melanoma development. As development of successful therapies strongly depends on clinically relevant preclinical models, together with the new findings, more advanced melanoma models have been generated. In this article, besides traditional mouse models of melanoma, we will discuss recent ones, such as patient-derived tumor xenografts, topically inducible BRAF mouse model and RCAS/TVA-based model, and their advantages as well as limitations. Although mouse models of melanoma are often criticized as poor predictors of whether an experimental drug would be an effective treatment, development of new and more relevant models could circumvent this problem in the near future.

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.

Clinical skill development for community pharmacists.

PubMed

Barnette, D J; Murphy, C M; Carter, B L

1996-09-01

The importance of establishing clinical pharmacy services in the community cannot be understated in light of current challenges to the traditional dispensing role as the primary service of the community pharmacist. Advancements in automated dispensing technology and declining prescription fee reimbursement are rapidly forcing pharmacists to seek alternative sources of revenue. Providing pharmaceutical care is a viable option to increase customer loyalty job satisfaction, and reimbursement. To support the development of clinical services, academic institutions are forming partnerships with individual community practitioners to overcome perceived educational and training barriers. The authors describe the design and development of two unique clinical skill development programs at the University of Illinois at Chicago. This paper also outlines the patient focused services that the participants have established upon completing the training. These programs successfully enhanced participants' therapeutic knowledge base and facilitated development of the clinical skills necessary for direct patient care.

A Clinical Assessment Tool for Advanced Theory of Mind Performance in 5 to 12 Year Olds

ERIC Educational Resources Information Center

O'Hare, Anne E.; Bremner, Lynne; Nash, Marysia; Happe, Francesca; Pettigrew, Luisa M.

2009-01-01

One hundred forty typically developing 5- to 12-year-old children were assessed with a test of advanced theory of mind employing Happe's strange stories. There was no significant difference in performance between boys and girls. The stories discriminated performance across the different ages with the lowest performance being in the younger…

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.

Longitudinal Ultrasound Education Track Curriculum Implemented Within an Emergency Medicine Residency Program.

PubMed

Boulger, Creagh; Adams, Daniel Z; Hughes, Daralee; Bahner, David P; King, Andrew

2017-06-01

Emergency Medicine residency programs offer ultrasound-focused curricula to address Accreditation Council for Graduate Medical Education (ACGME) milestones. Although some programs offer advanced clinical tracks in ultrasound, no standard curriculum exists. We sought to establish a well-defined ultrasound track curriculum to allow interested residents to develop advanced clinical skills and scholarship within this academic niche. The curriculum involves a greater number of clinical scans, ultrasound-focused scholarly and quality improvement projects, enhanced faculty-driven ultrasound focused didactics, and participation at a national ultrasound conference to receive certification. Successful ultrasound scholarly tracks can provide residents with the potential to obtain fellowships or competency beyond ACGME requirements. © 2017 by the American Institute of Ultrasound in Medicine.

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.

A critical assessment of boron target compounds for boron neutron capture therapy.

PubMed

Hawthorne, M Frederick; Lee, Mark W

2003-01-01

Boron neutron capture therapy (BNCT) has undergone dramatic developments since its inception by Locher in 1936 and the development of nuclear energy during World War II. The ensuing Cold War spawned the entirely new field of polyhedral borane chemistry, rapid advances in nuclear reactor technology and a corresponding increase in the number to reactors potentially available for BNCT. This effort has been largely oriented toward the eradication of glioblastoma multiforme (GBM) and melanoma with reduced interest in other types of malignancies. The design and synthesis of boron-10 target compounds needed for BNCT was not channeled to those types of compounds specifically required for GBM or melanoma. Consequently, a number of potentially useful boron agents are known which have not been biologically evaluated beyond a cursory examination and only three boron-10 enriched target species are approved for human use following their Investigational New Drug classification by the US Food and Drug Administration; BSH, BPA and GB-10. All ongoing clinical trials with GBM and melanoma are necessarily conducted with one of these three species and most often with BPA. The further development of BNCT is presently stalled by the absence of strong support for advanced compound evaluation and compound discovery driven by recent advances in biology and chemistry. A rigorous demonstration of BNCT efficacy surpassing that of currently available protocols has yet to be achieved. This article discusses the past history of compound development, contemporary problems such as compound classification and those problems which impede future advances. The latter include means for biological evaluation of new (and existing) boron target candidates at all stages of their development and the large-scale synthesis of boron target species for clinical trials and beyond. The future of BNCT is bright if latitude is given to the choice of clinical disease to be treated and if a recognized study demonstrating improved efficacy is completed. Eventually, BNCT in some form will be commercialized.

Revisiting the Biomedicalization of Aging: Clinical Trends and Ethical Challenges

ERIC Educational Resources Information Center

Kaufman, Sharon R.; Shim, Janet K.; Russ, Ann J.

2004-01-01

Developments in the realms of medical innovation and geriatric clinical intervention impact our understanding of the nature of late life, the possibilities for health in advanced age, medical decision making, and family responsibility in ways that could not have been predicted 15 years ago. This essay begins to map new forms of biomedicalization…

Practitioner's Guide to Assessment of Autism Spectrum Disorders in Infants and Toddlers

ERIC Educational Resources Information Center

Steiner, Amanda Mossman; Goldsmith, Tina R.; Snow, Anne V.; Chawarska, Katarzyna

2012-01-01

Recent advances in clinical research have made it possible to diagnosis autism spectrum disorders (ASD) as early as the second year of life. The diagnostic process early in development is often complex, and thus, familiarity with the most recent findings in clinical assessment instruments, early symptoms, and developmental trajectories of young…

Integration of gene expression, clinical, and demographic information in relation to asthma status to identify biomarkers associated with subtypes of childhood asthma

EPA Science Inventory

Advances in biomarker development have improved our ability to detect early changes at the molecular, cellular, and pre-clinical level that are often predictive of adverse health outcomes. Biomarkers for monitoring the underlying molecular mechanisms of disease are of increasing...

Recommendations for Planning Pilot Studies in Clinical and Translational Research

PubMed Central

Moore, Charity G.; Carter, Rickey E.; Nietert, Paul J.; Stewart, Paul W.

2011-01-01

Abstract  Advances in clinical and translation science are facilitated by building on prior knowledge gained through experimentation and observation. In the context of drug development, preclinical studies are followed by a progression of phase I through phase IV clinical trials. At each step, the study design and statistical strategies are framed around research questions that are prerequisites for the next phase. In other types of biomedical research, pilot studies are used for gathering preliminary support for the next research step. However, the phrase “pilot study” is liberally applied to projects with little or no funding, characteristic of studies with poorly developed research proposals, and usually conducted with no detailed thought of the subsequent study. In this article, we present a rigorous definition of a pilot study, offer recommendations for the design, analysis and sample size justification of pilot studies in clinical and translational research, and emphasize the important role that well‐designed pilot studies play in the advancement of science and scientific careers. Clin Trans Sci 2011; Volume 4: 332–337 PMID:22029804

Pathways and therapeutic targets in melanoma

PubMed Central

Shtivelman, Emma; Davies, Michael A.; Hwu, Patrick; Yang, James; Lotem, Michal; Oren, Moshe; Flaherty, Keith T.; Fisher, David E.

2014-01-01

This review aims to summarize the current knowledge of molecular pathways and their clinical relevance in melanoma. Metastatic melanoma was a grim diagnosis, but in recent years tremendous advances have been made in treatments. Chemotherapy provided little benefit in these patients, but development of targeted and new immune approaches made radical changes in prognosis. This would not have happened without remarkable advances in understanding the biology of disease and tremendous progress in the genomic (and other “omics”) scale analyses of tumors. The big problems facing the field are no longer focused exclusively on the development of new treatment modalities, though this is a very busy area of clinical research. The focus shifted now to understanding and overcoming resistance to targeted therapies, and understanding the underlying causes of the heterogeneous responses to immune therapy. PMID:24743024

WE-F-201-00: Practical Guidelines for Commissioning Advanced Brachytherapy Dose Calculation Algorithms

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

NONE

2015-06-15

With the recent introduction of heterogeneity correction algorithms for brachytherapy, the AAPM community is still unclear on how to commission and implement these into clinical practice. The recently-published AAPM TG-186 report discusses important issues for clinical implementation of these algorithms. A charge of the AAPM-ESTRO-ABG Working Group on MBDCA in Brachytherapy (WGMBDCA) is the development of a set of well-defined test case plans, available as references in the software commissioning process to be performed by clinical end-users. In this practical medical physics course, specific examples on how to perform the commissioning process are presented, as well as descriptions of themore » clinical impact from recent literature reporting comparisons of TG-43 and heterogeneity-based dosimetry. Learning Objectives: Identify key clinical applications needing advanced dose calculation in brachytherapy. Review TG-186 and WGMBDCA guidelines, commission process, and dosimetry benchmarks. Evaluate clinical cases using commercially available systems and compare to TG-43 dosimetry.« less

An American Clinical Training Program for Spanish Nutrition Support Pharmacists: A Three-Year Experience

PubMed Central

Dickerson, Roland N.; Martinez, Eva M.; Fraile, M. Carmen; Giménez, Josefina; Calvo, M. Victoria

2015-01-01

A clinical nutrition support pharmacist training program, in collaboration with the Spanish Foundation of Hospital Pharmacy, Spanish Society of Clinical Nutrition, Abbott Nutrition International, University of Tennessee, College of Pharmacy and Regional One Health, is described. Nutrition support pharmacists from Spain were selected to participate in a one-month training program with an experienced board-certified nutrition support pharmacist faculty member within an interdisciplinary nutrition support team environment in the U.S. Participants were expected to actively engage in an advanced clinical practice role with supervision. Clinical activities included daily intensive patient monitoring, physical assessment, critical evaluation of the patient and development of an appropriate treatment plan for patients receiving either enteral or parenteral nutrition therapy. Upon successful completion of the training program, participants were anticipated to incorporate these techniques into their current practice in Spain and to train other pharmacists to function in an advanced clinical role independently or within an interdisciplinary nutrition support team environment. PMID:28975899

Leading by Success: Impact of a Clinical & Translational Research Infrastructure Program to Address Health Inequities

PubMed Central

Shiramizu, Bruce; Shambaugh, Vicki; Petrovich, Helen; Seto, Todd B.; Ho, Tammy; Mokuau, Noreen; Hedges, Jerris R.

2016-01-01

Building research infrastructure capacity to address clinical and translational gaps has been a focus of funding agencies and foundations. Clinical and Translational Sciences Awards, Research Centers in Minority Institutions Infrastructure for Clinical and Translational Research (RCTR) and the Institutional Development Award Infrastructure for Clinical and Translational Research funded by United States (US) government to fund clinical translational research programs have existed for over a decade to address racial and ethnic health disparities across the US. While the impact on the nation’s health can’t be made in a short period, assessment of a program’s impact could be a litmus test to gauge its effectiveness at the institution and communities. We report the success of a Pilot Project Program in the University of Hawaii RCTR Award in advancing careers of emerging investigators and community collaborators. Our findings demonstrated that the investment has a far-reaching impact on engagement with community-based research collaborators, career advancement of health disparities investigators, and favorable impacts on health policy. PMID:27797013

Vitamin E in human skin: organ-specific physiology and considerations for its use in dermatology.

PubMed

Thiele, Jens J; Ekanayake-Mudiyanselage, Swarna

2007-01-01

Vitamin E has been used for more than 50 years in experimental and clinical dermatology. While a large number of case reports were published in this time, there is still a lack of controlled clinical studies providing a rationale for well defined dosages and clinical indications. In contrast, advances in basic research on the physiology, mechanism of action, penetration, bioconversion and photoprotection of vitamin E in human skin has led to the development of numerous new formulations for use in cosmetics and skin care products. This article reviews basic mechanisms and possible cosmetic as well as clinical implications of the recent advances in cutaneous vitamin E research. Experimental evidence suggests that topical and oral vitamin E has antitumorigenic, photoprotective, and skin barrier stabilizing properties. While the current use of vitamin E is largely limited to cosmetics, controlled clinical studies for indications such as atopic dermatitis or preventions of photocarcinogenesis are needed to evaluate the clinical benefit of vitamin E.

Transforming RN education: clinical learning and clinical knowledge development.

PubMed

Benner, P

1993-04-01

Transforming RN education has the potential for transforming clinical teaching and learning for all students. The returning RN student offers possibilities for clinical learning that the generic student does not have, but this should not cause us to limit the returning RN student to the generic level. Where possible innovative programs should be developed to move the RN student from baccalaureate level to the Master's level. As educators, we should take the opportunity to increase the numbers of nurses who are educationally prepared to move into advanced levels of practice. The returning RN student offers a rich human resource for the profession, and a rich resource for improving our clinical teaching as well as our practice.

[Achievements of an educational strategy promoting participation in the development of clinical aptitude and critical reading in cardiology residents, linked to appropriate use of research reports].

PubMed

Valencia-Sánchez, Jesús Salvador; Leyva-González, Félix Arturo; Viniegra-Velázquez, Leonardo

2007-01-01

To search the reach of educative strategy promoting the participation, to estimate the development of clinical aptitude and critical reading attaching the appropriate use of clinic research in cardiology residents. Prospective study. The instrument of clinical aptitude was constructed with five cases and 170 items and the instrument of critical reading was developed with five summaries of articles of clinical research in cardiology by 120 items. The strategy was performed with activities one a week during six months by two hours per class, in the period: March and September, 2005. Reading guides were delivered to the participants a week before that included a clinical case and clinic research of cardiology. During the activities in class we were promoting the participation and discussion. Both measuring instruments were performed in the first (initial measuring) and final session (final measuring). Non parametric test were used because the variable of the subjects were not normal distribution and the scale was ordinal. The reliability coefficient in both instruments with the Kuder-Richardson was 0.90 and 0.85 respectively. After educative strategy was observed a significant advance in the global calcifications, such as in critical reading and in clinical aptitude (p = 0.001 and 0.5 respectively). Analyzing in an independent manner the components of critical reading we found significant advancement in the indicators interpretation and judgment. In clinical aptitude we found significant progress in the indicators: the suitable use of paraclinics resources, the appropriate use of therapeutics measurement and iatropatogenic decisions for omission. The educative strategy promoting the participation, permitted to get a change in the clinical aptitude and critical reading attaching the appropriate use of sources of investigation in cardiology residents.

Practical Applications of Digital Pathology.

PubMed

Saeed-Vafa, Daryoush; Magliocco, Anthony M

2015-04-01

Virtual microscopy and advances in machine learning have paved the way for the ever-expanding field of digital pathology. Multiple image-based computing environments capable of performing automated quantitative and morphological analyses are the foundation on which digital pathology is built. The applications for digital pathology in the clinical setting are numerous and are explored along with the digital software environments themselves, as well as the different analytical modalities specific to digital pathology. Prospective studies, case-control analyses, meta-analyses, and detailed descriptions of software environments were explored that pertained to digital pathology and its use in the clinical setting. Many different software environments have advanced platforms capable of improving digital pathology and potentially influencing clinical decisions. The potential of digital pathology is vast, particularly with the introduction of numerous software environments available for use. With all the digital pathology tools available as well as those in development, the field will continue to advance, particularly in the era of personalized medicine, providing health care professionals with more precise prognostic information as well as helping them guide treatment decisions.

METastasis Reporting and Data System for Prostate Cancer: Practical Guidelines for Acquisition, Interpretation, and Reporting of Whole-body Magnetic Resonance Imaging-based Evaluations of Multiorgan Involvement in Advanced Prostate Cancer.

PubMed

Padhani, Anwar R; Lecouvet, Frederic E; Tunariu, Nina; Koh, Dow-Mu; De Keyzer, Frederik; Collins, David J; Sala, Evis; Schlemmer, Heinz Peter; Petralia, Giuseppe; Vargas, H Alberto; Fanti, Stefano; Tombal, H Bertrand; de Bono, Johann

2017-01-01

Comparative reviews of whole-body magnetic resonance imaging (WB-MRI) and positron emission tomography/computed tomography (CT; with different radiotracers) have shown that metastasis detection in advanced cancers is more accurate than with currently used CT and bone scans. However, the ability of WB-MRI and positron emission tomography/CT to assess therapeutic benefits has not been comprehensively evaluated. There is also considerable variability in the availability and quality of WB-MRI, which is an impediment to clinical development. Expert recommendations for standardising WB-MRI scans are needed, in order to assess its performance in advanced prostate cancer (APC) clinical trials. To design recommendations that promote standardisation and diminish variations in the acquisition, interpretation, and reporting of WB-MRI scans for use in APC. An international expert panel of oncologic imagers and oncologists with clinical and research interests in APC management assessed biomarker requirements for clinical care and clinical trials. Key requirements for a workable WB-MRI protocol, achievable quality standards, and interpretation criteria were identified and synthesised in a white paper. The METastasis Reporting and Data System for Prostate Cancer guidelines were formulated for use in all oncologic manifestations of APC. Uniformity in imaging data acquisition, quality, and interpretation of WB-MRI are essential for assessing the test performance of WB-MRI. The METastasis Reporting and Data System for Prostate Cancer standard requires validation in clinical trials of treatment approaches in APC. METastasis Reporting and Data System for Prostate Cancer represents the consensus recommendations on the performance, quality standards, and reporting of whole-body magnetic resonance imaging, for use in all oncologic manifestations of advanced prostate cancer. These new criteria require validation in clinical trials of established and new treatment approaches in advanced prostate cancer. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Career development resource: academic career in surgical education.

PubMed

Sanfey, Hilary; Gantt, Nancy L

2012-07-01

Academic surgeons play an instrumental role in the training of our medical students and surgical residents. Although volunteer faculty often have an important role in the clinical development of surgeons-in-training, the tasks of curricular development, structured didactic sessions, professional advising, research sponsorship, and mentoring at all levels fall to the academic surgeon. Historically, the career advancement path for an academic physician favored grant acquisition and scholarly publication. Broader definitions of scholarship have emerged, along with corresponding modifications in academic award systems that allow advancement in faculty rank based on a surgeon's educational efforts. Copyright © 2012 Elsevier Inc. All rights reserved.

Gaining momentum: New options and opportunities for the treatment of advanced melanoma.

PubMed

Michielin, Olivier; Hoeller, Christoph

2015-09-01

Before 2011, patients with advanced or metastatic melanoma had a particularly poor long-term prognosis. Since traditional treatments failed to confer a survival benefit, patients were preferentially entered into clinical trials of investigational agents. A greater understanding of the epidemiology and biology of disease has underpinned the development of newer therapies, including six agents that have been approved in the EU, US and/or Japan: a cytotoxic T-lymphocyte antigen-4 inhibitor (ipilimumab), two programmed cell death-1 receptor inhibitors (nivolumab and pembrolizumab), two BRAF inhibitors (vemurafenib and dabrafenib) and a MEK inhibitor (trametinib). The availability of these treatments has greatly improved the outlook for patients with advanced melanoma; however, a major consideration for physicians is now to determine how best to integrate these agents into clinical practice. Therapeutic decisions are complicated by the need to consider patient and disease characteristics, and individual treatment goals, alongside the different efficacy and safety profiles of agents with varying mechanisms of action. Long-term survival, an outcome largely out of reach with traditional systemic therapies, is now a realistic goal, creating the additional need to re-establish how clinical benefit is evaluated. In this review we summarise the current treatment landscape in advanced melanoma and discuss the promise of agents still in development. We also speculate on the future of melanoma treatment and discuss how combination and sequencing approaches may be used to optimise patient care in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinical trials: bringing research to the bedside.

PubMed

Arvay, C A

1991-02-01

Over the years, clinical trials with their structured treatment plans and multicenter involvement have been instrumental in developing new treatments and establishing standard of care therapy. While clinical trials strive to advance medical knowledge, they provide scientifically sound, state of the art care and their use should be increased. The Brain Tumor Cooperative Group, one such NCI-sponsored cooperative group, has been the primary group for the treatment of malignant gliomas. As the field of neuro-oncology expands, the neuroscience nurse needs to develop an understanding of clinical trials and their operation. The nurse is in an optimal position to support medical research and the research participant.

Antiviral therapeutics for the treatment of Ebola virus infection.

PubMed

Cardile, Anthony P; Downey, Lydia G; Wiseman, Perry D; Warren, Travis K; Bavari, Sina

2016-10-01

There have been significant developments in Ebola virus therapeutics. While the efficacy of several products was evaluated in the recent West Africa outbreak, a licensed treatment for EBOV disease remains elusive. Factors that negatively impacted the execution of clinical trials included an overall lack of world readiness to conduct clinical trials in an outbreak setting, ethical concerns limiting implementation of the randomized controlled trials in an outbreak setting, and a decline in case numbers by the time resources were mobilized to conduct clinical trials. We summarize relevant therapeutics that underwent clinical trials during the West Africa outbreak and highlight promising candidates under advanced development. Published by Elsevier Ltd.

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 data from residency program directors provides support for developing new assessment tools in high-stakes licensing examinations.

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 year of residency training or later. Conclusions Gathering data from residency program directors provides support for developing new assessment tools in high-stakes licensing examinations. PMID:22833698

Evanescent wave fluorescence biosensors: Advances of the last decade

PubMed Central

Taitt, Chris Rowe; Anderson, George P.; Ligler, Frances S.

2015-01-01

Biosensor development has been a highly dynamic field of research and has progressed rapidly over the past two decades. The advances have accompanied the breakthroughs in molecular biology, nanomaterial sciences, and most importantly computers and electronics. The subfield of evanescent wave fluorescence biosensors has also matured dramatically during this time. Fundamentally, this review builds on our earlier 2005 review. While a brief mention of seminal early work will be included, this current review will focus on new technological developments as well as technology commercialized in just the last decade. Evanescent wave biosensors have found a wide array applications ranging from clinical diagnostics to biodefense to food testing; advances in those applications and more are described herein. PMID:26232145

Advances in Bioprinting Technologies for Craniofacial Reconstruction.

PubMed

Visscher, Dafydd O; Farré-Guasch, Elisabet; Helder, Marco N; Gibbs, Susan; Forouzanfar, Tymour; van Zuijlen, Paul P; Wolff, Jan

2016-09-01

Recent developments in craniofacial reconstruction have shown important advances in both the materials and methods used. While autogenous tissue is still considered to be the gold standard for these reconstructions, the harvesting procedure remains tedious and in many cases causes significant donor site morbidity. These limitations have subsequently led to the development of less invasive techniques such as 3D bioprinting that could offer possibilities to manufacture patient-tailored bioactive tissue constructs for craniofacial reconstruction. Here, we discuss the current technological and (pre)clinical advances of 3D bioprinting for use in craniofacial reconstruction and highlight the challenges that need to be addressed in the coming years. Copyright © 2016 Elsevier Ltd. All rights reserved.

Performance of children and adolescents with Asperger syndrome or high-functioning autism on advanced theory of mind tasks.

PubMed

Kaland, Nils; Callesen, Kirsten; Møller-Nielsen, Annette; Mortensen, Erik Lykke; Smith, Lars

2008-07-01

Although a number of advanced theory of mind tasks have been developed, there is a dearth of information on whether performances on different tasks are associated. The present study examined the performance of 21 children and adolescents with diagnoses of Asperger syndrome (AS) and 20 typically developing controls on three advanced theory of mind tasks: The Eyes Task, the Strange Stories, and the Stories from Everyday Life. The participants in the clinical group demonstrated lower performance than the controls on all the three tasks. The pattern of findings, however, indicates that these tasks may share different information-processing requirements in addition to tapping different mentalizing abilities.

Clinical Correlations as a Tool in Basic Science Medical Education

PubMed Central

Klement, Brenda J.; Paulsen, Douglas F.; Wineski, Lawrence E.

2016-01-01

Clinical correlations are tools to assist students in associating basic science concepts with a medical application or disease. There are many forms of clinical correlations and many ways to use them in the classroom. Five types of clinical correlations that may be embedded within basic science courses have been identified and described. (1) Correlated examples consist of superficial clinical information or stories accompanying basic science concepts to make the information more interesting and relevant. (2) Interactive learning and demonstrations provide hands-on experiences or the demonstration of a clinical topic. (3) Specialized workshops have an application-based focus, are more specialized than typical laboratory sessions, and range in complexity from basic to advanced. (4) Small-group activities require groups of students, guided by faculty, to solve simple problems that relate basic science information to clinical topics. (5) Course-centered problem solving is a more advanced correlation activity than the others and focuses on recognition and treatment of clinical problems to promote clinical reasoning skills. Diverse teaching activities are used in basic science medical education, and those that include clinical relevance promote interest, communication, and collaboration, enhance knowledge retention, and help develop clinical reasoning skills. PMID:29349328

Nomograms Predicting Progression-Free Survival, Overall Survival, and Pelvic Recurrence in Locally Advanced Cervical Cancer Developed From an Analysis of Identifiable Prognostic Factors in Patients From NRG Oncology/Gynecologic Oncology Group Randomized Trials of Chemoradiotherapy

PubMed Central

Rose, Peter G.; Java, James; Whitney, Charles W.; Stehman, Frederick B.; Lanciano, Rachelle; Thomas, Gillian M.; DiSilvestro, Paul A.

2015-01-01

Purpose To evaluate the prognostic factors in locally advanced cervical cancer limited to the pelvis and develop nomograms for 2-year progression-free survival (PFS), 5-year overall survival (OS), and pelvic recurrence. Patients and Methods We retrospectively reviewed 2,042 patients with locally advanced cervical carcinoma enrolled onto Gynecologic Oncology Group clinical trials of concurrent cisplatin-based chemotherapy and radiotherapy. Nomograms for 2-year PFS, five-year OS, and pelvic recurrence were created as visualizations of Cox proportional hazards regression models. The models were validated by bootstrap-corrected, relatively unbiased estimates of discrimination and calibration. Results Multivariable analysis identified prognostic factors including histology, race/ethnicity, performance status, tumor size, International Federation of Gynecology and Obstetrics stage, tumor grade, pelvic node status, and treatment with concurrent cisplatin-based chemotherapy. PFS, OS, and pelvic recurrence nomograms had bootstrap-corrected concordance indices of 0.62, 0.64, and 0.73, respectively, and were well calibrated. Conclusion Prognostic factors were used to develop nomograms for 2-year PFS, 5-year OS, and pelvic recurrence for locally advanced cervical cancer clinically limited to the pelvis treated with concurrent cisplatin-based chemotherapy and radiotherapy. These nomograms can be used to better estimate individual and collective outcomes. PMID:25732170

microRNAs as cancer therapeutics: A step closer to clinical application.

PubMed

Catela Ivkovic, Tina; Voss, Gjendine; Cornella, Helena; Ceder, Yvonne

2017-10-28

During the last decades, basic and translational research has enabled great improvements in the clinical management of cancer. However, scarcity of complete remission and many drug-induced toxicities are still a major problem in the clinics. Recently, microRNAs (miRNAs) have emerged as promising therapeutic targets due to their involvement in cancer development and progression. Their extraordinary regulatory potential, which enables regulation of entire signalling networks within the cells, makes them an interesting tool for the development of cancer therapeutics. In this review we will focus on miRNAs with experimentally proven therapeutic potential, and discuss recent advances in the technical development and clinical evaluation of miRNA-based therapeutic agents. Copyright © 2017 Elsevier B.V. All rights reserved.

Accelerating Next Generation Vaccine Development for Global Disease Prevention

PubMed Central

Koff, Wayne C; Burton, Dennis R.; R.Johnson, Philip; Walker, Bruce D.; King, Charles R.; Nabel, Gary J.; Ahmed, Rafi; Bhan, Maharaj Kishan; Plotkin, Stanley A.

2014-01-01

Summary Vaccines are among the greatest successes in the history of public health. However, past strategies for vaccine development are unlikely to succeed in the future against major global diseases such as AIDS, TB, and malaria. For such diseases, the correlates of protection are poorly defined and the pathogens evade immune detection and/or exhibit extensive genetic variability. Recent advances have heralded in a new era of vaccine discovery. However, translation of these advances into vaccines remains impeded by lack of understanding of key vaccinology principles in humans. We review these advances towards vaccine discovery and suggest that for accelerating successful vaccine development, new human immunology-based clinical research initiatives be implemented with the goal of elucidating and more effectively inducing vaccine-induced protective immune responses. PMID:23723240

Advancing nursing scholarship: the Mozambique model

PubMed Central

Bruce, Judith C.; Dippenaar, Joan; Schmollgruber, Shelley; Mphuthi, David D.; Huiskamp, Agnes

2017-01-01

ABSTRACT Background: Despite the importance of Human Resources for Health for the development and functioning of health systems worldwide, many countries continue to be plagued by poor health systems and a lack of adequate health care. Health systems failures may be attributed to both quantitative and qualitative nursing shortages including the lack of advanced skills to lead health initiatives, to conduct research and to educate other nurses. The response by development partners is usually framed around the production of skilled nurses through the processes of up-skilling and scaling-up. The outcome is expanded practice but with scant attention to the professional advancement of nurses. Objectives: In this paper we present a two-phased capacity development model that adopted professionalization strategies to advance nursing scholarship and consequent postgraduate specialization of the first cohort of nurses in Mozambique. The main objectives were to: develop and implement a clinical course work master’s degree in nursing; and ensure sustainability by capacitating the host institution to continue with the master’s programme following graduation. Methods: Rigorous processes for project discussions, negotiations and monitoring were necessary amid limited resources and a challenging political climate. Forging in-country partnerships, sustaining alliances and government investment are thus key to the success of the Mozambique model. Outcomes: Notwithstanding some difficulties, the process unfolded over a five-year period, graduating the first cohort of 11 senior nurses with a master’s degree, specializing either in critical care and trauma nursing, or maternal and neonatal health. Conclusions: Bridging the skills gap between generalist and specialist nurses is essential for them to manage complex and high acuity cases and to reverse associated morbidity and mortality. We conclude that this model serves as a professionalization strategy to advance nurses’ scholarship of clinical practice, research and teaching. PMID:28771092

Approach for a Clinically Useful Comprehensive Classification of Vascular and Neural Aspects of Diabetic Retinal Disease

PubMed Central

Abramoff, Michael D.; Fort, Patrice E.; Han, Ian C.; Jayasundera, K. Thiran; Sohn, Elliott H.; Gardner, Thomas W.

2018-01-01

The Early Treatment Diabetic Retinopathy Study (ETDRS) and other standardized classification schemes have laid a foundation for tremendous advances in the understanding and management of diabetic retinopathy (DR). However, technological advances in optics and image analysis, especially optical coherence tomography (OCT), OCT angiography (OCTa), and ultra-widefield imaging, as well as new discoveries in diabetic retinal neuropathy (DRN), are exposing the limitations of ETDRS and other classification systems to completely characterize retinal changes in diabetes, which we term diabetic retinal disease (DRD). While it may be most straightforward to add axes to existing classification schemes, as diabetic macular edema (DME) was added as an axis to earlier DR classifications, doing so may make these classifications increasingly complicated and thus clinically intractable. Therefore, we propose future research efforts to develop a new, comprehensive, and clinically useful classification system that will identify multimodal biomarkers to reflect the complex pathophysiology of DRD and accelerate the development of therapies to prevent vision-threatening DRD. PMID:29372250

Approach for a Clinically Useful Comprehensive Classification of Vascular and Neural Aspects of Diabetic Retinal Disease.

PubMed

Abramoff, Michael D; Fort, Patrice E; Han, Ian C; Jayasundera, K Thiran; Sohn, Elliott H; Gardner, Thomas W

2018-01-01

The Early Treatment Diabetic Retinopathy Study (ETDRS) and other standardized classification schemes have laid a foundation for tremendous advances in the understanding and management of diabetic retinopathy (DR). However, technological advances in optics and image analysis, especially optical coherence tomography (OCT), OCT angiography (OCTa), and ultra-widefield imaging, as well as new discoveries in diabetic retinal neuropathy (DRN), are exposing the limitations of ETDRS and other classification systems to completely characterize retinal changes in diabetes, which we term diabetic retinal disease (DRD). While it may be most straightforward to add axes to existing classification schemes, as diabetic macular edema (DME) was added as an axis to earlier DR classifications, doing so may make these classifications increasingly complicated and thus clinically intractable. Therefore, we propose future research efforts to develop a new, comprehensive, and clinically useful classification system that will identify multimodal biomarkers to reflect the complex pathophysiology of DRD and accelerate the development of therapies to prevent vision-threatening DRD.

Clinically Applicable Inhibitors Impacting Genome Stability.

PubMed

Prakash, Anu; Garcia-Moreno, Juan F; Brown, James A L; Bourke, Emer

2018-05-13

Advances in technology have facilitated the molecular profiling (genomic and transcriptomic) of tumours, and has led to improved stratification of patients and the individualisation of treatment regimes. To fully realize the potential of truly personalised treatment options, we need targeted therapies that precisely disrupt the compensatory pathways identified by profiling which allow tumours to survive or gain resistance to treatments. Here, we discuss recent advances in novel therapies that impact the genome (chromosomes and chromatin), pathways targeted and the stage of the pathways targeted. The current state of research will be discussed, with a focus on compounds that have advanced into trials (clinical and pre-clinical). We will discuss inhibitors of specific DNA damage responses and other genome stability pathways, including those in development, which are likely to synergistically combine with current therapeutic options. Tumour profiling data, combined with the knowledge of new treatments that affect the regulation of essential tumour signalling pathways, is revealing fundamental insights into cancer progression and resistance mechanisms. This is the forefront of the next evolution of advanced oncology medicine that will ultimately lead to improved survival and may, one day, result in many cancers becoming chronic conditions, rather than fatal diseases.

Clinical development of Ebola vaccines

PubMed Central

Sridhar, Saranya

2015-01-01

The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines. PMID:26668751

European Vaccine Initiative: lessons from developing malaria vaccines.

PubMed

Geels, Mark J; Imoukhuede, Egeruan B; Imbault, Nathalie; van Schooten, Harry; McWade, Terry; Troye-Blomberg, Marita; Dobbelaer, Roland; Craig, Alister G; Leroy, Odile

2011-12-01

For over 10 years, the European Vaccine Initiative (EVI; European Malaria Vaccine Initiative until 2009) has contributed to the development of 24 malaria candidate vaccine antigens with 13 vaccine candidates being advanced into Phase I clinical trials, two of which have been transitioned for further clinical development in sub-Saharan Africa. Since its inception the EVI organization has operated as a funding agency, but with a clear service-oriented strategy. The scientific successes and difficulties encountered during these years and how these efforts have led to standardization and harmonization in vaccine development through large-scale European consortia are discussed. In the future, the EVI will remain instrumental in the pharmaceutical and clinical development of vaccines against 'diseases of poverty' with a continued focus on malaria. EVI will continue to focus on funding and managing preclinical evaluation up to Phase I/II clinical trials and strengthening the vaccine-development infrastructure in Europe, albeit with a global orientation.

Focused development of advanced practice nurse roles for specific patient groups in a Swiss university hospital

PubMed

Spichiger, Elisabeth; Zumstein-Shaha, Maya; Schubert, Maria; Herrmann, Luzia

2018-02-01

Background: To cover future health care needs of the population, new care models are necessary. The development of advanced nursing practice (ANP) offers the opportunity to meet these challenges with novel services. At the Inselspital, Bern University Hospital, ANP services and corresponding advanced practice nurse (APN) roles have been developed since 2011. Purpose: The aim is to develop innovative and evidence based ANP services to supplement health care for specific patient groups and their family members with the goal to improve safety and achieve better outcomes. Methods: Project-based ANP services are developed in close collaboration of clinical departments and the Nursing Development Unit (NDU) of the Directorate of Nursing. Structure, process and outcome data are collected for evaluation. Findings: Currently, five ANP services are established and running, eight more are in the developmental phase. Most services address the long term care of patients with chronic illnesses and their family members. Ten APNs work between 10 % and 80 %, three are leading an ANP-team. APNs work over 50 % in direct clinical practice, primarily in counselling. An ANP network connects APNs and NDU, promoting synergy and exchange. Conclusions: The available resources often constitute a challenge for the development of ANP services. Vital for the long-term success are an adequate extent of the position, the support by department directorate, the conceptual framework that is implemented across the whole hospital, and the development within project structures.

Development and Validation of a Multidisciplinary Mobile Care System for Patients With Advanced Gastrointestinal Cancer: Interventional Observation Study.

PubMed

Soh, Ji Yeong; Cha, Won Chul; Chang, Dong Kyung; Hwang, Ji Hye; Kim, Kihyung; Rha, Miyong; Kwon, Hee

2018-05-07

Mobile health apps have emerged as supportive tools in the management of advanced cancers. However, only a few apps have self-monitoring features, and they are not standardized and validated. This study aimed to develop and validate a multidisciplinary mobile care system with self-monitoring features that can be useful for patients with advanced gastrointestinal cancer. The development of the multidisciplinary mobile health management system was divided into 3 steps. First, the service scope was set up, and the measurement tools were standardized. Second, the service flow of the mobile care system was organized. Third, the mobile app (Life Manager) was developed. The app was developed to achieve 3 major clinical goals: support for quality of life, nutrition, and rehabilitation. Three main functional themes were developed to achieve clinical goals: a to-do list, health education, and in-app chat. Thirteen clinically oriented measures were included: the modified Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events questionnaire, Scored Patient-Generated Subjective Global Assessment (PG-SGA), distress, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, International Physical Activity Questionnaire-Short Form, Low anterior resection syndrome score, satisfaction rate, etc. To validate the system, a prospective observational study was conducted. Patients with gastric cancer or colon cancer undergoing chemotherapy were recruited. We followed the subjects for 12 weeks, and selected clinical measures were taken online and offline. After the development process, a multidisciplinary app, the Life Manager, was launched. For evaluation, 203 patients were recruited for the study, of whom 101 (49.8%) had gastric cancer, and 102 (50.2%) were receiving palliative care. Most patients were in their fifties (35.5%), and 128 (63.1%) were male. Overall, 176 subjects (86.7%) completed the study. Among subjects who dropped out, the most common reason was the change of patient's clinical condition (51.9%). During the study period, subjects received multiple health education sessions. For the gastric cancer group, the "general gastric cancer education" was most frequently viewed (322 times), and for the colon cancer group, the "warming-up exercise" was most viewed (340 times). Of 13 measurements taken from subjects, 9 were taken offline (response rate: 52.0% to 90.1%), and 3 were taken online (response rate: 17.6% to 57.4%). The overall satisfaction rate among subjects was favorable and ranged from 3.93 (SD 0.88) to 4.01 (SD 0.87) on the 5-point Likert scale. A multidisciplinary mobile care system for patients with advanced gastrointestinal cancer was developed with clinically oriented measures. A prospective study was performed for its evaluation, which showed favorable satisfaction. ©Ji Yeong Soh, Won Chul Cha, Dong Kyung Chang, Ji Hye Hwang, Kihyung Kim, Miyong Rha, Hee Kwon. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 07.05.2018.

Improving patient outcomes in fibrous dysplasia/McCune-Albright syndrome: an international multidisciplinary workshop to inform an international partnership.

PubMed

Boyce, A M; Turner, A; Watts, L; Forestier-Zhang, L; Underhill, A; Pinedo-Villanueva, R; Monsell, F; Tessaris, D; Burren, C; Masi, L; Hamdy, N; Brandi, M L; Chapurlat, R; Collins, M T; Javaid, Muhammad Kassim

2017-12-01

To develop consensus on improving the management of patients, we convened an international workshop involving patients, clinicians, and researchers. Key findings included the diagnostic delay and variability in subsequent management with agreement to develop an international natural history study. We now invite other stakeholders to join the partnership. The aim of this study was develop a consensus on how to improve the management of patients with fibrous dysplasia and prioritize areas for research METHODS: An international workshop was held over 3 days involving patients, clinicians, and researchers. Each day had a combination of formal presentations and facilitated discussions that focused on clinical pathways and research. The patient workshop day highlighted the variability of patients' experience in getting a diagnosis, the knowledge of general clinical staff, and understanding long-term outcomes. The research workshop prioritized collaborations that improved understanding of the contemporary natural history of fibrous dysplasia/McCune-Albright syndrome (FD/MAS). The clinical workshop outlined the key issues around diagnostics, assessment of severity, treatment and monitoring of patients. In spite of advances in understanding the genetic and molecular underpinnings of fibrous dysplasia/McCune-Albright syndrome, clinical management remains a challenge. From the workshop, a consensus was reached to create an international, multi-stakeholder partnership to advance research and clinical care in FD/MAS. We invite other stakeholders to join the partnership.

Medical technology advances from space research

NASA Technical Reports Server (NTRS)

Pool, S. L.

1972-01-01

Details of medical research and development programs, particularly an integrated medical laboratory, as derived from space technology are given. The program covers digital biotelemetry systems, automatic visual field mapping equipment, sponge electrode caps for clinical electroencephalograms, and advanced respiratory analysis equipment. The possibility of using the medical laboratory in ground based remote areas and regional health care facilities, as well as long duration space missions is discussed.

Proceedings: Regenerative Medicine for Lung Diseases: A CIRM Workshop Report.

PubMed

Kadyk, Lisa C; DeWitt, Natalie D; Gomperts, Brigitte

2017-10-01

The mission of the California Institute of Regenerative Medicine (CIRM) is to accelerate treatments to patients with unmet medical needs. In September 2016, CIRM sponsored a workshop held at the University of California, Los Angeles, to discuss regenerative medicine approaches for treatment of lung diseases and to identify the challenges remaining for advancing such treatments to the clinic and market approval. Workshop participants discussed current preclinical and clinical approaches to regenerative medicine in the lung, as well as the biology of lung stem cells and the role of stem cells in the etiology of various lung diseases. The outcome of this effort was the recognition that whereas transient cell delivery approaches are leading the way in the clinic, recent advances in the understanding of lung stem cell biology, in vitro and in vivo disease modeling, gene editing and replacement methods, and cell engraftment approaches raise the prospect of developing cures for some lung diseases in the foreseeable future. In addition, advances in in vitro modeling using lung organoids and "lung on a chip" technology are setting the stage for high quality small molecule drug screening to develop treatments for lung diseases with complex biology. Stem Cells Translational Medicine 2017;6:1823-1828. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Malignant Bowel Obstruction in Advanced Gynecologic Cancers: An Updated Review from a Multidisciplinary Perspective

PubMed Central

Lee, Yeh Chen; Jivraj, Nazlin; O'Brien, Catherine; Chawla, Tanya; Shlomovitz, Eran; Buchanan, Sarah; Lau, Jenny; Croke, Jennifer; Allard, Johane P.; Dhar, Preeti; Laframboise, Stephane; Ferguson, Sarah E.; Dhani, Neesha; Butler, Marcus; Ng, Pamela; Stuart-McEwan, Terri; Savage, Pamela; Tinker, Lisa; Oza, Amit M.

2018-01-01

Malignant bowel obstruction (MBO) is a major complication in women with advanced gynecologic cancers which imposes a significant burden on patients, caregivers, and healthcare systems. Symptoms of MBO are challenging to palliate and result in progressive decompensation of already vulnerable patients with limited therapeutic options and a short prognosis. However, there is a paucity of guidelines or innovative approaches to improve the care of women who develop MBO. MBO is a complex clinical situation that requires a multidisciplinary approach to ensure the appropriate treatment modality and interprofessional care to optimally manage these patients. This review summarizes the current literature on the different approaches targeting MBO management including surgical intervention, chemotherapy, total parenteral nutrition, and pharmacological treatment. In addition, the impact of MBO management on patients' quality of life (QOL) is examined. This article focuses on the challenges in developing evidence-based treatment guidelines for MBO and barriers in clinical trial design for MBO and proposes strategies to advance the MBO management. Collaboration is essential to design studies that may improve the overall care and quality of life for these patients. Prospective data are needed to inform clinical practice, establish a new benchmark for evidence-based MBO management, and better understand the biology of MBO. PMID:29887891

Computational techniques for ECG analysis and interpretation in light of their contribution to medical advances

PubMed Central

Mincholé, Ana; Martínez, Juan Pablo; Laguna, Pablo; Rodriguez, Blanca

2018-01-01

Widely developed for clinical screening, electrocardiogram (ECG) recordings capture the cardiac electrical activity from the body surface. ECG analysis can therefore be a crucial first step to help diagnose, understand and predict cardiovascular disorders responsible for 30% of deaths worldwide. Computational techniques, and more specifically machine learning techniques and computational modelling are powerful tools for classification, clustering and simulation, and they have recently been applied to address the analysis of medical data, especially ECG data. This review describes the computational methods in use for ECG analysis, with a focus on machine learning and 3D computer simulations, as well as their accuracy, clinical implications and contributions to medical advances. The first section focuses on heartbeat classification and the techniques developed to extract and classify abnormal from regular beats. The second section focuses on patient diagnosis from whole recordings, applied to different diseases. The third section presents real-time diagnosis and applications to wearable devices. The fourth section highlights the recent field of personalized ECG computer simulations and their interpretation. Finally, the discussion section outlines the challenges of ECG analysis and provides a critical assessment of the methods presented. The computational methods reported in this review are a strong asset for medical discoveries and their translation to the clinical world may lead to promising advances. PMID:29321268

Targeting thyroid diseases with TSH receptor analogs.

PubMed

Galofré, Juan C; Chacón, Ana M; Latif, Rauf

2013-12-01

The thyroid-stimulating hormone (TSH) receptor (TSHR) is a major regulator of thyroid function and growth, and is the key antigen in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Various effective treatment strategies are currently available for many of these clinical conditions such as antithyroid drugs or radioiodine therapy, but they are not devoid of side effects. In addition, treatment of complications of Graves' disease such as Graves' ophthalmopathy is often difficult and unsatisfactory using current methods. Recent advances in basic research on both in vitro and in vivo models have suggested that TSH analogs could be used for diagnosis and treatment of some of the thyroid diseases. The advent of high-throughput screening methods has resulted in a group of TSH analogs called small molecules, which have the potential to be developed as promising drugs. Small molecules are low molecular weight compounds with agonist, antagonist and, in some cases, inverse agonist activity on TSHR. This short review will focus on current advances in development of TSH analogs and their potential clinical applications. Rapid advances in this field may lead to the conduct of clinical trials of small molecules related to TSHR for the management of Graves' disease, thyroid cancer, and thyroid-related osteoporosis in the coming years. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

In situ photoimmunotherapy for melanoma: an ongoing phase I clinical trial

NASA Astrophysics Data System (ADS)

Naylor, Mark F.; Nordquist, Robert E.; Teague, T. Kent; Perry, Lisa A.; Chen, Wei R.

2007-02-01

In situ Photoimmunotherapy (ISPI) was developed to treat metastatic tumors using a combination of phototherapy and immunotherapy. It utilizes local intervention through photothermal destruction of existing solid tumors and through immune response modifier to elicit host anti-tumor responses. Such combination in pre-clinical studies has shown promise in cancer treatment by eradicating the primary tumors and also controlling metastases at distant sites. ISPI has been used in our preliminary clinical studies for melanoma patients and the outcome has been extremely encouraging. In 2006, we began enrolling patients in a new phase I immunotherapy trial for advanced cutaneous melanoma. This trial is based on our previous results which indicated that we had developed an effective treatment for advanced melanoma. Of the first six patients treated, (4 stage IV, and 2 surgically unresectable stage III), 2 of the stage IV patients are still alive, one tumor free, and one with a possible treatable recurrence after 2 1/2 years. We have also discovered that recurrences of the skin cancer can be retreated by the same technique and that treatment seems to blunt the virulence of the disease and make it more treatable. These initial results indicate that ISPI probably will have the ability to prolong survival in selected cases of advanced melanoma, and potentially cure a significant percentage of treated patients.

Implications of pharmacogenomics for drug development and clinical practice.

PubMed

Ginsburg, Geoffrey S; Konstance, Richard P; Allsbrook, Jennifer S; Schulman, Kevin A

2005-11-14

Pharmacogenomics is likely to be among the first clinical applications of the Human Genome Project and is certain to have an enormous impact on the clinical practice of medicine. Herein, we discuss the potential implications of pharmacogenomics on the drug development process, including drug safety, productivity, market segmentation, market expansion, differentiation, and personalized health care. We also review 3 challenges facing the translation of pharmacogenomics into clinical practice: dependence on information technology, limited health care financing, and the scientific uncertainty surrounding validation of specific applications of the technology. To our knowledge, there is currently no formal agenda to promote and cultivate innovation, to develop progressive information technology, or to obtain the financing that would be required to advance the use of pharmacogenomic technologies in patient care. Although the potential of these technologies is driving change in the development of clinical sciences, it remains to be seen which health care systems level needs will be addressed.

The Development, Commercialization, and Impact of Optical Coherence Tomography

PubMed Central

Fujimoto, James; Swanson, Eric

2016-01-01

This review was written for the special issue of IOVS to describe the history of optical coherence tomography (OCT) and its evolution from a nonscientific, historic perspective. Optical coherence tomography has become a standard of care in ophthalmology, providing real-time information on structure and function – diagnosing disease, evaluating progression, and assessing response to therapy, as well as helping to understand disease pathogenesis and create new therapies. Optical coherence tomography also has applications in multiple clinical specialties, fundamental research, and manufacturing. We review the early history of OCT describing how research and development evolves and the important role of multidisciplinary collaboration and expertise. Optical coherence tomography had its origin in femtosecond optics, but used optical communications technologies and required advanced engineering for early OCT prototypes, clinical feasibility studies, entrepreneurship, and corporate development in order to achieve clinical acceptance and clinical impact. Critical advances were made by early career researchers, clinician scientists, engineering experts, and business leaders, which enabled OCT to have a worldwide impact on health care. We introduce the concept of an “ecosystem” consisting of research, government funding, collaboration and competition, clinical studies, innovation, entrepreneurship and industry, and impact – all of which must work synergistically. The process that we recount is long and challenging, but it is our hope that it might inspire early career professionals in science, engineering, and medicine, and that the clinical and research community will find this review of interest. PMID:27409459

Technological progress and challenges towards cGMP manufacturing of human pluripotent stem cells based therapeutic products for allogeneic and autologous cell therapies.

PubMed

Abbasalizadeh, Saeed; Baharvand, Hossein

2013-12-01

Recent technological advances in the generation, characterization, and bioprocessing of human pluripotent stem cells (hPSCs) have created new hope for their use as a source for production of cell-based therapeutic products. To date, a few clinical trials that have used therapeutic cells derived from hESCs have been approved by the Food and Drug Administration (FDA), but numerous new hPSC-based cell therapy products are under various stages of development in cell therapy-specialized companies and their future market is estimated to be very promising. However, the multitude of critical challenges regarding different aspects of hPSC-based therapeutic product manufacturing and their therapies have made progress for the introduction of new products and clinical applications very slow. These challenges include scientific, technological, clinical, policy, and financial aspects. The technological aspects of manufacturing hPSC-based therapeutic products for allogeneic and autologous cell therapies according to good manufacturing practice (cGMP) quality requirements is one of the most important challenging and emerging topics in the development of new hPSCs for clinical use. In this review, we describe main critical challenges and highlight a series of technological advances in all aspects of hPSC-based therapeutic product manufacturing including clinical grade cell line development, large-scale banking, upstream processing, downstream processing, and quality assessment of final cell therapeutic products that have brought hPSCs closer to clinical application and commercial cGMP manufacturing. © 2013.

Multiscale Modeling in the Clinic: Drug Design and Development

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

Clancy, Colleen E.; An, Gary; Cannon, William R.

A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multi-scale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multi-scale approaches present in silico opportunities to advance laboratory research to bedside clinical applications in pharmaceuticals research. This is achievable through the capability of modeling to reveal phenomena occurring across multiple spatial and temporal scales, which are not otherwise readily accessible to experimentation. The resultant models, when validated, are capable of making testable predictions tomore » guide drug design and delivery. In this review we describe the goals, methods, and opportunities of multi-scale modeling in drug design and development. We demonstrate the impact of multiple scales of modeling in this field. We indicate the common mathematical techniques employed for multi-scale modeling approaches used in pharmacology and present several examples illustrating the current state-of-the-art regarding drug development for: Excitable Systems (Heart); Cancer (Metastasis and Differentiation); Cancer (Angiogenesis and Drug Targeting); Metabolic Disorders; and Inflammation and Sepsis. We conclude with a focus on barriers to successful clinical translation of drug development, drug design and drug delivery multi-scale models.« less

Evolution of Clinical Proteomics and its Role in Medicine | Office of Cancer Clinical Proteomics Research

Cancer.gov

NCI's Office of Cancer Clinical Proteomics Research authored a review of the current state of clinical proteomics in the peer-reviewed Journal of Proteome Research. The review highlights outcomes from the CPTC program and also provides a thorough overview of the different technologies that have pushed the field forward. Additionally, the review provides a vision for moving the field forward through linking advances in genomic and proteomic analysis to develop new, molecularly targeted interventions.

Clinical Pharmacology & Therapeutics: Past, Present, and Future.

PubMed

Waldman, S A; Terzic, A

2017-03-01

Clinical Pharmacology & Therapeutics (CPT), the definitive and timely source for advances in human therapeutics, transcends the drug discovery, development, regulation, and utilization continuum to catalyze, evolve, and disseminate discipline-transformative knowledge. Prioritized themes and multidisciplinary content drive the science and practice of clinical pharmacology, offering a trusted point of reference. An authoritative herald across global communities, CPT is a timeless information vehicle at the vanguard of discovery, translation, and application ushering therapeutic innovation into modern healthcare. © 2017 American Society for Clinical Pharmacology and Therapeutics.

School-Based Clinics: A Guide for Advocates. Developing Policy Statements, Educating Decision Makers, Enlisting Local Support.

ERIC Educational Resources Information Center

Center for Population Options, Washington, DC.

School-based clinics (SBCs) are comprehensive primary health care facilities located within or on the grounds of middle, junior, or senior high schools. Varying in size and organizational structure, SBCs have emerged as an effective model for advancing adolescent health. They have gained attention because of their potential for treating problems…

Developing and using online courses to prepare nurses for employment in critical care.

PubMed

Billings, Diane M; Jeffries, Pamela R; Daniels, Dawn Marie; Rowles, Connie; Stone, Cynthia L; Stephenson, Evelyn

2006-01-01

Using online courses is one way to simplify orientation programs and leverage educator resources. Three critical care courses were created using a distributed authoring model with geographically diverse clinical experts. A companion online orientation course prepares preceptors to assist with clinical application. Course outcomes include preparation for practice, career mobility/advancement, and learner satisfaction.

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.

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

Sponsors meet scientists to speed pediatric medicines development.

PubMed

Davis, Jonathan M; Smoyer, William E; Connor, Edward M; Huskins, W Charles; Pastern, Cindy; Purucker, Mary; Schrader, Elisabeth C; Jackson, Cynthia R; Kaskel, Frederick J; Hirschfeld, Steven

2015-03-18

The Point-Person Project, a child-health research initiative, enables rapid response to opportunities for participation in multicenter pediatric clinical trials. Copyright © 2015, American Association for the Advancement of Science.

SGLT2 inhibitors: a promising new therapeutic option for treatment of type 2 diabetes mellitus.

PubMed

Misra, Monika

2013-03-01

Hyperglycemia is an important pathogenic component in the development of microvascular and macrovascular complications in type 2 diabetes mellitus. Inhibition of renal tubular glucose reabsorption that leads to glycosuria has been proposed as a new mechanism to attain normoglycemia and thus prevent and diminish these complications. Sodium glucose cotransporter 2 (SGLT2) has a key role in reabsorption of glucose in kidney. Competitive inhibitors of SGLT2 have been discovered and a few of them have also been advanced in clinical trials for the treatment of diabetes. To discuss the therapeutic potential of SGLT2 inhibitors currently in clinical development. A number of preclinical and clinical studies of SGLT2 inhibitors have demonstrated a good safety profile and beneficial effects in lowering plasma glucose levels, diminishing glucotoxicity, improving glycemic control and reducing weight in diabetes. Of all the SGLT2 inhibitors, dapagliflozin is a relatively advanced compound with regards to clinical development. SGLT2 inhibitors are emerging as a promising therapeutic option for the treatment of diabetes. Their unique mechanism of action offers them the potential to be used in combination with other oral anti-diabetic drugs as well as with insulin. © 2012 The Author. JPP © 2012 Royal Pharmaceutical Society.

Faculty verbal evaluations reveal strategies used to promote medical student performance

PubMed Central

Hauer, Karen E.; Mazotti, Lindsay; O'Brien, Bridget; Hemmer, Paul A.; Tong, Lowell

2011-01-01

Background Preceptors rarely follow medical students' developing clinical performance over time and across disciplines. This study analyzes preceptors' descriptions of longitudinal integrated clerkship (LIC) students' clinical development and their identification of strategies to guide students' progress. Methods We used a common evaluation framework, reporter-interpreter-manager-educator, to guide multidisciplinary LIC preceptors' discussions of students' progress. We conducted thematic analysis of transcripts from preceptors' (seven longitudinal ambulatory preceptors per student) quarterly group discussions of 15 students' performance over one year. Results All students' clinical development progressed, although most experienced obstacles. Lack of structure in the history and physical exam commonly obstructed progression. Preceptors used templates for data gathering, and modeling or experiences in the inpatient setting to provide time and solidify structure. To advance students' knowledge acquisition, many preceptors identified focused learning topics with their students; to promote application of knowledge, preceptors used reasoning strategies to teach the steps involved in synthesizing clinical data. Preceptors shared accountability for helping students advance as the LIC allowed them to follow students' response to teaching strategies. Discussion These results depict preceptors' perceptions of LIC students' developmental continuum and illustrate how multidisciplinary preceptors can use a common evaluation framework to identify strategies to improve performance and follow students' performance longitudinally. PMID:21629669

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.

Vemurafenib: a new treatment for BRAF-V600 mutated advanced melanoma

PubMed Central

Fisher, Rosalie; Larkin, James

2012-01-01

The BRAF inhibitor, vemurafenib, has demonstrated improved progression-free and overall survival compared with chemotherapy in a randomized trial, and represents a new standard of care in patients with advanced melanoma harboring a BRAF-V600 mutation. A BRAF-V600 mutation is identified in approximately half of patients with cutaneous melanoma, and is unequivocally a biomarker predictive of profound clinical benefit for these patients. However, acquired vemurafenib resistance is a major clinical challenge and therapy is not yet curative. A substantial body of translational research has been performed alongside clinical trials of vemurafenib, providing key insights into the molecular basis of response and resistance. This review summarizes the development of vemurafenib for the treatment of BRAF-V600 mutant melanoma and discusses how knowledge of critical signaling pathways will be applied for its optimal clinical use in future. PMID:22904646

Defining Advance Care Planning for Adults: A Consensus Definition from a Multidisciplinary Delphi Panel

PubMed Central

Sudore, Rebecca L.; Lum, Hillary D.; You, John J.; Hanson, Laura C.; Meier, Diane E.; Pantilat, Steven Z.; Matlock, Daniel D.; Rietjens, Judith A. C.; Korfage, Ida J.; Ritchie, Christine S.; Kutner, Jean S.; Teno, Joan M.; Thomas, Judy; McMahan, Ryan D.; Heyland, Daren K.

2017-01-01

Background Despite increasing interest in advance care planning (ACP) and prior ACP descriptions, a consensus definition does not yet exist to guide clinical, research, and policy initiatives. Objective To develop a consensus definition of ACP for adults. Design Delphi Panel Setting/Participants Participants included a multidisciplinary panel of international ACP experts consisting of 52 clinicians, researchers, and policy leaders from 4 countries, and a patient/surrogate advisory committee. Measurements We conducted 10 rounds of a modified Delphi method and qualitatively analyzed panelists’ input. Panelists identified several themes lacking consensus, and iteratively discussed and developed a final consensus definition. Results Panelists identified several tensions concerning ACP concepts such as whether the definition should focus on conversations vs. written advance directives; patients’ values vs. treatment preferences; current shared decision making vs. future medical decisions; and who should be included in the process. The panel achieved a final consensus one-sentence definition and accompanying goals statement: “Advance care planning is a process that supports adults at any age or stage of health in understanding and sharing their personal values, life goals, and preferences regarding future medical care. The goal of advance care planning is to help ensure that people receive medical care that is consistent with their values, goals and preferences during serious and chronic illness.” The panel also described strategies to best support adults in ACP. Conclusions A multidisciplinary Delphi panel developed a consensus definition for ACP for adults that can be used to inform implementation and measurement of ACP clinical, research, and policy initiatives. PMID:28062339

Defining Advance Care Planning for Adults: A Consensus Definition From a Multidisciplinary Delphi Panel.

PubMed

Sudore, Rebecca L; Lum, Hillary D; You, John J; Hanson, Laura C; Meier, Diane E; Pantilat, Steven Z; Matlock, Daniel D; Rietjens, Judith A C; Korfage, Ida J; Ritchie, Christine S; Kutner, Jean S; Teno, Joan M; Thomas, Judy; McMahan, Ryan D; Heyland, Daren K

2017-05-01

Despite increasing interest in advance care planning (ACP) and previous ACP descriptions, a consensus definition does not yet exist to guide clinical, research, and policy initiatives. The aim of this study was to develop a consensus definition of ACP for adults. We convened a Delphi panel of multidisciplinary, international ACP experts consisting of 52 clinicians, researchers, and policy leaders from four countries and a patient/surrogate advisory committee. We conducted 10 rounds using a modified Delphi method and qualitatively analyzed panelists' input. Panelists identified several themes lacking consensus and iteratively discussed and developed a final consensus definition. Panelists identified several tensions concerning ACP concepts such as whether the definition should focus on conversations vs. written advance directives; patients' values vs. treatment preferences; current shared decision making vs. future medical decisions; and who should be included in the process. The panel achieved a final consensus one-sentence definition and accompanying goals statement: "Advance care planning is a process that supports adults at any age or stage of health in understanding and sharing their personal values, life goals, and preferences regarding future medical care. The goal of advance care planning is to help ensure that people receive medical care that is consistent with their values, goals and preferences during serious and chronic illness." The panel also described strategies to best support adults in ACP. A multidisciplinary Delphi panel developed a consensus definition for ACP for adults that can be used to inform implementation and measurement of ACP clinical, research, and policy initiatives. Published by Elsevier Inc.

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

[Targeted therapies in hepatocellular carcinomas: recent results and future development].

PubMed

Marijon, H; Faivre, S; Raymond, E

2009-05-01

Hepatocellular carcinoma (HCC) is one of the 5th most common cancers around the world with a limited number of systemic therapeutic options. Cytotoxic agents, hormonotherapy and immunotherapy have failed to demonstrate benefit compared to best supportive care in patients with advanced HCC. The recent development of targeted therapies provided hope for the treatment of advanced HCC. We reviewed phases II-III trials presented in 2007 and 2008. Results are promising with a clinical benefit reported with molecular therapies targeting EGF/EGFR and VEGF/VEGFR pathways.

Tenofovir-based rescue therapy for advanced liver disease in 6 patients coinfected with HIV and hepatitis B virus and receiving lamivudine.

PubMed

Gutiérrez, Sonia; Guillemi, Silvia; Jahnke, Natalie; Montessori, Valentina; Harrigan, P Richard; Montaner, Julio S G

2008-02-01

We summarize the clinical history and laboratory results following the introduction of tenofovir among 6 patients coinfected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) who presented with severe liver disease while receiving lamivudine-based highly active antiretroviral therapy. In all cases, the introduction of tenofovir led to a sustained undetectable HBV and HIV loads, with marked clinical and laboratory improvement in liver function. We provide supporting evidence for the role of tenofovir in the management of advanced HBV infection in HIV-positive patients after the development of lamivudine resistance.

Diagnosis and Management of Acute Concussion.

PubMed

McCrea, Michael A; Nelson, Lindsay D; Guskiewicz, Kevin

2017-05-01

Over the past 2 decades, there have been major advances in the basic and clinical science of concussion and mild traumatic brain injury. These advances now provide a more evidence-informed approach to the definition, diagnosis, assessment, and management of acute concussion. Standardized clinical tools have been developed and validated for assessment of acute concussion across injury settings (eg, civilian, sport, military). Consensus guidelines now provide guidance regarding injury management and approaches to ensure safe return to activity after acute concussion. This article provides a brief, high-level overview of approaches to best practice in diagnosis, assessment, and management of acute concussion. Copyright © 2017 Elsevier Inc. All rights reserved.

High-intensity focused ultrasound: advances in technology and experimental trials support enhanced utility of focused ultrasound surgery in oncology

PubMed Central

Malietzis, G; Monzon, L; Hand, J; Wasan, H; Leen, E; Abel, M; Muhammad, A; Abel, P

2013-01-01

High-intensity focused ultrasound (HIFU) is a rapidly maturing technology with diverse clinical applications. In the field of oncology, the use of HIFU to non-invasively cause tissue necrosis in a defined target, a technique known as focused ultrasound surgery (FUS), has considerable potential for tumour ablation. In this article, we outline the development and underlying principles of HIFU, overview the limitations and commercially available equipment for FUS, then summarise some of the recent technological advances and experimental clinical trials that we predict will have a positive impact on extending the role of FUS in cancer therapy. PMID:23403455

[Gemcitabine and non small-cell lung cancer].

PubMed

Vignot, Stéphane; Besse, Benjamin

2007-01-01

Questions raised during gemcitabine development reflect non small-cell lung cancer (NSCLC) history during last 10 years. Third generation therapies (gemcitabine, vinorelbine and taxanes) combined with platinium compounds are now to be prescribed in almost all clinical situations, from surgically removed tumors to metastatic diseases. The 30% response rate usually reported in advanced disease (with a median survival of 10 months) has to be improved and a more global approach is nowadays mandatory, including targeted agents. This review sum-up the clinical situations in which gemcitabine can be prescribed (advanced disease), or shall be prescribed (adjuvant setting, combination with anti-angiogenic agent or EGFR inhibitors), and highlight opening questions.

[Research advances of anti-tumor immune response induced by pulse electric field ablation].

PubMed

Cui, Guang-ying; Diao, Hong-yan

2015-11-01

As a novel tumor therapy, pulse electric field has shown a clinical perspective. This paper reviews the characteristics of tumor ablation by microsecond pulse and nanosecond pulse electric field, and the research advances of anti-tumor immune response induced by pulse electric field ablation. Recent researches indicate that the pulse electric field not only leads to a complete ablation of local tumor, but also stimulates a protective immune response, thereby inhibiting tumor recurrence and metastasis. These unique advantages will show an extensive clinical application in the future. However, the mechanism of anti-tumor immune response and the development of related tumor vaccine need further studies.

Advanced MR Imaging of the Placenta: Exploring the in utero placenta-brain connection

PubMed Central

Andescavage, Nickie Niforatos; DuPlessis, Adre; Limperopoulos, Catherine

2015-01-01

The placenta is a vital organ necessary for the healthy neurodevelopment of the fetus. Despite the known associations between placental dysfunction and neurologic impairment, there is a paucity of tools available to reliably assess in vivo placental health and function. Existing clinical tools for placental assessment remain insensitive in predicting and assessing placental well-being. Advanced MRI techniques hold significant promise for the dynamic, non-invasive, real-time assessment of placental health and identification of early placental-based disorders. In this review, we summarize the available clinical tools for placental assessment including ultrasound, Doppler, and conventional MRI. We then explore the emerging role of advanced placental MR imaging techniques for supporting the developing fetus, appraise the strengths and limitations of quantitative MRI in identifying early markers of placental dysfunction for improved pregnancy monitoring and fetal outcomes. PMID:25765905

Clinical proteomic biomarkers: relevant issues on study design & technical considerations in biomarker development

PubMed Central

2014-01-01

Biomarker research is continuously expanding in the field of clinical proteomics. A combination of different proteomic–based methodologies can be applied depending on the specific clinical context of use. Moreover, current advancements in proteomic analytical platforms are leading to an expansion of biomarker candidates that can be identified. Specifically, mass spectrometric techniques could provide highly valuable tools for biomarker research. Ideally, these advances could provide with biomarkers that are clinically applicable for disease diagnosis and/ or prognosis. Unfortunately, in general the biomarker candidates fail to be implemented in clinical decision making. To improve on this current situation, a well-defined study design has to be established driven by a clear clinical need, while several checkpoints between the different phases of discovery, verification and validation have to be passed in order to increase the probability of establishing valid biomarkers. In this review, we summarize the technical proteomic platforms that are available along the different stages in the biomarker discovery pipeline, exemplified by clinical applications in the field of bladder cancer biomarker research. PMID:24679154

Biodegradable lipids enabling rapidly eliminated lipid nanoparticles for systemic delivery of RNAi therapeutics.

PubMed

Maier, Martin A; Jayaraman, Muthusamy; Matsuda, Shigeo; Liu, Ju; Barros, Scott; Querbes, William; Tam, Ying K; Ansell, Steven M; Kumar, Varun; Qin, June; Zhang, Xuemei; Wang, Qianfan; Panesar, Sue; Hutabarat, Renta; Carioto, Mary; Hettinger, Julia; Kandasamy, Pachamuthu; Butler, David; Rajeev, Kallanthottathil G; Pang, Bo; Charisse, Klaus; Fitzgerald, Kevin; Mui, Barbara L; Du, Xinyao; Cullis, Pieter; Madden, Thomas D; Hope, Michael J; Manoharan, Muthiah; Akinc, Akin

2013-08-01

In recent years, RNA interference (RNAi) therapeutics, most notably with lipid nanoparticle-based delivery systems, have advanced into human clinical trials. The results from these early clinical trials suggest that lipid nanoparticles (LNPs), and the novel ionizable lipids that comprise them, will be important materials in this emerging field of medicine. A persistent theme in the use of materials for biomedical applications has been the incorporation of biodegradability as a means to improve biocompatibility and/or to facilitate elimination. Therefore, the aim of this work was to further advance the LNP platform through the development of novel, next-generation lipids that combine the excellent potency of the most advanced lipids currently available with biodegradable functionality. As a representative example of this novel class of biodegradable lipids, the lipid evaluated in this work displays rapid elimination from plasma and tissues, substantially improved tolerability in preclinical studies, while maintaining in vivo potency on par with that of the most advanced lipids currently available.

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 reconstructed (pre, 33.3 ± 4.5 vs post, 35.9 ± 5.0; p = 0.008) and standard Pediatric Advanced Life Support (pre, 30.5 ± 4.7 vs post, 33.6 ± 4.9; p = 0.02), with no significant difference of improvement between both groups (p = 0.49). For PICU-based nurses and respiratory therapists, simulation-based "Pediatric Advanced Life Support-reconstructed" in situ training is feasible and more effective than standard Pediatric Advanced Life Support recertification training for skill performance. Both Pediatric Advanced Life Support recertification training courses improved behavioral performance.

Therapeutic implication of HER2 in advanced biliary tract cancer

PubMed Central

Cha, Yongjun; Ha, Hyerim; Park, Ji Eun; Bang, Ju-Hee; Jin, Mei Hua; Lee, Kyung-Hun; Kim, Tae-Yong; Han, Sae-Won; Im, Seock-Ah; Kim, Tae-You; Oh, Do-Youn; Bang, Yung-Jue

2016-01-01

Currently, there is no validated therapeutic target for biliary tract cancer (BTC). This study aimed to investigate the pre-clinical and clinical implication of HER2 as a therapeutic target in BTC. We established two novel HER2-amplified BTC cell lines, SNU-2670 and SNU-2773, from gallbladder cancer patients. SNU-2670 and SNU-2773 cells were sensitive to trastuzumab, dacomitinib, and afatinib compared with nine HER2-negative BTC cell lines. Dacomitinib and afatinib led to G1 cell cycle arrest in SNU-2773 cells and apoptosis in SNU-2670 cells. Furthermore, dacomitinib, afatinib, and trastuzumab showed synergistic cytotoxicity when combined with some cytotoxic drugs including gemcitabine, cisplatin, paclitaxel, and 5-fluorouracil. In a SNU-2670 mouse xenograft model, trastuzumab demonstrated a good anti-tumor effect as a monotherapy and in combination with gemcitabine increasing apoptosis. In our clinical data, 13.0% of patients with advanced BTC were defined as HER2-positive. Of these, three patients completed HER2-targeted chemotherapy. Two of them demonstrated a partial response, and the other one showed stable disease for 18 weeks. In summary, these pre-clinical and clinical data suggest that HER2 could be a therapeutic target, and that a HER2-targeting strategy should be developed further in patients with HER2-positive advanced BTC. PMID:27517322

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.

Molecular targeted therapy in enteropancreatic neuroendocrine tumors: from biology to clinical practice.

PubMed

Fazio, N; Scarpa, A; Falconi, M

2014-01-01

Advanced enteropancreatic (EP) neuroendocrine tumors (NETs) can be treated with several different therapies, including chemotherapy, biotherapy, and locoregional treatments. Over the last few decades, impressive progress has been made in the biotherapy field. Three main druggable molecular targets have been studied and developed in terms of therapy: somatostatin receptor (sstr), mammalian target of rapamycin (mTOR), and angiogenic factors. In particular, research has moved from the old somatostatin analogs (SSAs), such as octreotide (OCT) and lanreotide (LAN), specifically binding to the sstr-2, to the newer pasireotide (PAS), which presents a wider sstr spectrum. Over the last ten years, several molecular targeted agents (MTAs) have been studied in phase II trials, and very few of them have reached phase III. The mTOR inhibitor everolimus and the multitargeted inhibitor sunitinib have been approved for clinical use by the FDA and EMA in advanced well/moderately-differentiated (WD, MD) progressive pancreatic neuroendocrine tumors (PNETs), on the basis of the positive results of two international large randomized phase III trials vs. placebo. Bevacizumab has been studied in a large US phase III trial vs. interferon (IFN)-alfa2b, and results are pending. In this review, the biological and clinical aspects of MTAs introduced into clinical practice or which are currently in an advanced phase of clinical investigation are addressed.

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.

International Conference on Advances in Radiation Oncology (ICARO): outcomes of an IAEA meeting.

PubMed

Salminen, Eeva K; Kiel, Krystyna; Ibbott, Geoffrey S; Joiner, Michael C; Rosenblatt, Eduardo; Zubizarreta, Eduardo; Wondergem, Jan; Meghzifene, Ahmed

2011-02-04

The IAEA held the International Conference on Advances in Radiation Oncology (ICARO) in Vienna on 27-29 April 2009. The Conference dealt with the issues and requirements posed by the transition from conventional radiotherapy to advanced modern technologies, including staffing, training, treatment planning and delivery, quality assurance (QA) and the optimal use of available resources. The current role of advanced technologies (defined as 3-dimensional and/or image guided treatment with photons or particles) in current clinical practice and future scenarios were discussed.ICARO was organized by the IAEA at the request of the Member States and co-sponsored and supported by other international organizations to assess advances in technologies in radiation oncology in the face of economic challenges that most countries confront. Participants submitted research contributions, which were reviewed by a scientific committee and presented via 46 lectures and 103 posters. There were 327 participants from 70 Member States as well as participants from industry and government. The ICARO meeting provided an independent forum for the interaction of participants from developed and developing countries on current and developing issues related to radiation oncology.

Advanced and recurring thymic carcinoma is target of new clinical trial | Center for Cancer Research

Cancer.gov

Adults diagnosed with thymic carcinoma who overexpress the protein mesothelin may be eligible to participate in a new clinical trial at the NIH Clinical Center. The study will look at the safety and effectiveness of an investigational drug, anetumab ravtansine, developed by Bayer HealthCare Pharmaceuticals. The drug works by binding to mesothelin, therefore overexpression of the protein could be useful for targeting cancer cells. Read more...

Diagnosis of schizophrenia: future ethics.

PubMed

McClelland, R

1997-01-01

The healthcare burden, to the affected individual, their family and to society, caused by the schizophrenias provides a strong moral appeal for non-discriminatory allocation of resources for both research and service provision. Nevertheless, the anticipated advances in clinical research findings are likely to lead to a new healthcare situation where a number of values and moral appeals are likely to be in conflict. The sources of these conflicts are explored with respect to the nature and origin of the schizophrenias, the challenges of pre-clinical and possible prenatal diagnosis. It is argued that the ethical problems associated with discovery of early markers for the development of schizophrenia should be anticipated and appropriate guidelines developed in advance of their realisation. Experience of other screening programmes strongly cautions against the introduction of such markers before the benefits and safety aspects have been clearly defined.

EU decision-making for marketing authorization of advanced therapy medicinal products: a case study.

PubMed

de Wilde, Sofieke; Coppens, Delphi G M; Hoekman, Jarno; de Bruin, Marie L; Leufkens, Hubert G M; Guchelaar, Henk-Jan; Meij, Pauline

2018-03-21

A comparative analysis of assessment procedures for authorization of all European Union (EU) applications for advanced therapy medicinal products (ATMPs) shows that negative opinions were associated with a lack of clinical efficacy and identified severe safety risks. Unmet medical need was often considered in positive opinions and outweighed scientific uncertainties. Numerous quality issues illustrate the difficulties in this domain for ATMP development. Altogether, it suggests that setting appropriate standards for ATMP authorization in Europe, similar to elsewhere, is a learning experience. The experimental characteristics of authorized ATMPs urge regulators, industry, and clinical practice to pay accurate attention to post-marketing risk management to limit patient risk. Methodologies for ATMP development and regulatory evaluations need to be continuously evaluated for the field to flourish. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Computational Medicine: Translating Models to Clinical Care

PubMed Central

Winslow, Raimond L.; Trayanova, Natalia; Geman, Donald; Miller, Michael I.

2013-01-01

Because of the inherent complexity of coupled nonlinear biological systems, the development of computational models is necessary for achieving a quantitative understanding of their structure and function in health and disease. Statistical learning is applied to high-dimensional biomolecular data to create models that describe relationships between molecules and networks. Multiscale modeling links networks to cells, organs, and organ systems. Computational approaches are used to characterize anatomic shape and its variations in health and disease. In each case, the purposes of modeling are to capture all that we know about disease and to develop improved therapies tailored to the needs of individuals. We discuss advances in computational medicine, with specific examples in the fields of cancer, diabetes, cardiology, and neurology. Advances in translating these computational methods to the clinic are described, as well as challenges in applying models for improving patient health. PMID:23115356

Pharmacokinetic de-risking tools for selection of monoclonal antibody lead candidates

PubMed Central

Dostalek, Miroslav; Prueksaritanont, Thomayant; Kelley, Robert F.

2017-01-01

ABSTRACT Pharmacokinetic studies play an important role in all stages of drug discovery and development. Recent advancements in the tools for discovery and optimization of therapeutic proteins have created an abundance of candidates that may fulfill target product profile criteria. Implementing a set of in silico, small scale in vitro and in vivo tools can help to identify a clinical lead molecule with promising properties at the early stages of drug discovery, thus reducing the labor and cost in advancing multiple candidates toward clinical development. In this review, we describe tools that should be considered during drug discovery, and discuss approaches that could be included in the pharmacokinetic screening part of the lead candidate generation process to de-risk unexpected pharmacokinetic behaviors of Fc-based therapeutic proteins, with an emphasis on monoclonal antibodies. PMID:28463063

Molecular biomarkers in idiopathic pulmonary fibrosis

PubMed Central

Ley, Brett; Brown, Kevin K.

2014-01-01

Molecular biomarkers are highly desired in idiopathic pulmonary fibrosis (IPF), where they hold the potential to elucidate underlying disease mechanisms, accelerated drug development, and advance clinical management. Currently, there are no molecular biomarkers in widespread clinical use for IPF, and the search for potential markers remains in its infancy. Proposed core mechanisms in the pathogenesis of IPF for which candidate markers have been offered include alveolar epithelial cell dysfunction, immune dysregulation, and fibrogenesis. Useful markers reflect important pathological pathways, are practically and accurately measured, have undergone extensive validation, and are an improvement upon the current approach for their intended use. The successful development of useful molecular biomarkers is a central challenge for the future of translational research in IPF and will require collaborative efforts among those parties invested in advancing the care of patients with IPF. PMID:25260757

Landscape of early clinical trials for childhood and adolescence cancer in Spain.

PubMed

Bautista, F; Gallego, S; Cañete, A; Mora, J; Diaz de Heredia, C; Cruz, O; Fernández, J M; Rives, S; Madero, L; Castel, V; Cela, M E; Ramírez, G; Sábado, C; Acha, T; Astigarraga, I; Sastre, A; Muñoz, A; Guibelalde, M; Moreno, L

2016-07-01

Despite numerous advances, survival remains dismal for children and adolescents with poor prognosis cancers or those who relapse or are refractory to first line treatment. There is, therefore, a major unmet need for new drugs. Recent advances in the knowledge of molecular tumor biology open the door to more adapted therapies according to individual alterations. Promising results in the adult anticancer drug development have not yet been translated into clinical practice. We report the activity in early pediatric oncology trials in Spain. All members of the Spanish Society of Pediatric Hematology Oncology (SEHOP) were contacted to obtain information about early trials open in each center. 22 phase I and II trials were open as of May 2015: 15 for solid tumors (68 %) and 7 for hematological malignancies (32 %). Fourteen (64 %) were industry sponsored. Since 2010, four centers have joined the Innovative Therapies For Children With Cancer, an international consortium whose aim is developing novel therapies for pediatric cancers. A substantial number of studies have opened in these 5 years, improving the portfolio of trials for children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents and their benefits. Clinical trials are the way to evaluate new drugs, avoiding the use of off-label drugs that carry significant risks. The Spanish pediatric oncology community through the SEHOP is committed to develop and participate in collaborative academic trials, to favor the advancement and optimization of existing therapies in pediatric cancer.

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

PubMed

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

2006-04-01

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

Contrast Media for X-ray and Magnetic Resonance Imaging: Development, Current Status and Future Perspectives.

PubMed

Frenzel, Thomas; Lawaczeck, Rüdiger; Taupitz, Matthias; Jost, Gregor; Lohrke, Jessica; Sieber, Martin A; Pietsch, Hubertus

2015-09-01

Over the last 120 years, the extensive advances in medical imaging allowed enhanced diagnosis and therapy of many diseases and thereby improved the quality of life of many patient generations. From the beginning, all technical solutions and imaging procedures were combined with dedicated pharmaceutical developments of contrast media, to further enhance the visualization of morphology and physiology. This symbiosis of imaging hardware and contrast media development was of high importance for the development of modern clinical radiology. Today, all available clinically approved contrast media fulfill the highest requirements for clinical safety and efficacy. All new concepts to increase the efficacy of contrast media have also to consider the high clinical safety standards and cost of goods of current marketed contrast media. Nevertheless, diagnostic imaging will contribute significantly to the progresses in medicine, and new contrast media developments are mandatory to address the medical needs of the future.

Initiative for Molecular Profiling and Advanced Cancer Therapy and challenges in the implementation of precision medicine.

PubMed

Tsimberidou, Apostolia-Maria

In the last decade, breakthroughs in technology have improved our understanding of genomic, transcriptional, proteomic, epigenetic aberrations and immune mechanisms in carcinogenesis. Genomics and model systems have enabled the validation of novel therapeutic strategies. Based on these developments, in 2007, we initiated the IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy) study, the first personalized medicine program for patients with advanced cancer at The University of Texas MD Anderson Cancer Center. We demonstrated that in patients referred for Phase I clinical trials, the use of tumor molecular profiling and treatment with matched targeted therapy was associated with encouraging rates of response, progression-free survival and overall survival compared to non-matched therapy. We are currently conducting IMPACT2, a randomized study evaluating molecular profiling and targeted agents in patients with metastatic cancer. Optimization of innovative biomarker-driven clinical trials that include targeted therapy and/or immunotherapeutic approaches for carefully selected patients will accelerate the development of novel drugs and the implementation of precision medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

The use of molecular imaging combined with genomic techniques to understand the heterogeneity in cancer metastasis

PubMed Central

Chowdhury, R; Ganeshan, B; Irshad, S; Lawler, K; Eisenblätter, M; Milewicz, H; Rodriguez-Justo, M; Miles, K; Ellis, P; Groves, A; Punwani, S

2014-01-01

Tumour heterogeneity has, in recent times, come to play a vital role in how we understand and treat cancers; however, the clinical translation of this has lagged behind advances in research. Although significant advancements in oncological management have been made, personalized care remains an elusive goal. Inter- and intratumour heterogeneity, particularly in the clinical setting, has been difficult to quantify and therefore to treat. The histological quantification of heterogeneity of tumours can be a logistical and clinical challenge. The ability to examine not just the whole tumour but also all the molecular variations of metastatic disease in a patient is obviously difficult with current histological techniques. Advances in imaging techniques and novel applications, alongside our understanding of tumour heterogeneity, have opened up a plethora of non-invasive biomarker potential to examine tumours, their heterogeneity and the clinical translation. This review will focus on how various imaging methods that allow for quantification of metastatic tumour heterogeneity, along with the potential of developing imaging, integrated with other in vitro diagnostic approaches such as genomics and exosome analyses, have the potential role as a non-invasive biomarker for guiding the treatment algorithm. PMID:24597512

Biology and clinical application of CAR T cells for B cell malignancies.

PubMed

Davila, Marco L; Sadelain, Michel

2016-07-01

Chimeric antigen receptor (CAR)-modified T cells have generated broad interest in oncology following a series of dramatic clinical successes in patients with chemorefractory B cell malignancies. CAR therapy now appears to be on the cusp of regulatory approval as a cell-based immunotherapy. We review here the T cell biology and cell engineering research that led to the development of second generation CARs, the selection of CD19 as a CAR target, and the preclinical studies in animal models that laid the foundation for clinical trials targeting CD19+ malignancies. We further summarize the status of CD19 CAR clinical therapy for non-Hodgkin lymphoma and B cell acute lymphoblastic leukemia, including their efficacy, toxicities (cytokine release syndrome, neurotoxicity and B cell aplasia) and current management in humans. We conclude with an overview of recent pre-clinical advances in CAR design that argues favorably for the advancement of CAR therapy to tackle other hematological malignancies as well as solid tumors.

Biology and clinical application of CAR T Cells for B cell malignancies

PubMed Central

Davila, Marco L; Sadelain, Michel

2017-01-01

Chimeric antigen receptor (CAR)-modified T cells have generated broad interest in oncology following a series of dramatic clinical successes in patients with chemorefractory B cell malignancies. CAR therapy now appears to be on the cusp of regulatory approval as a cell-based immunotherapy. We review here the T cell biology and cell engineering research that led to the development of second generation CARs, the selection of CD19 as a CAR target, and the preclinical studies in animal models that laid the foundation for clinical trials targeting CD19+ malignancies. We further summarize the status of CD19 CAR clinical therapy for non-Hodgkin lymphoma (NHL) and B cell acute lymphoblastic leukemia (B-ALL), including their efficacy, toxicities (cytokine release syndrome, neurotoxicity and B cell aplasia) and current management in humans. We conclude with an overview of recent pre-clinical advances in CAR design that argues favorably for the advancement of CAR therapy to tackle other hematological malignancies as well as solid tumors. PMID:27262700

Consensus Development from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014)

PubMed Central

Hsu, Chiun; Chen, Bang-Bin; Chen, Chien-Hung; Ho, Ming-Chih; Cheng, Jason Chia-Hsien; Kokudo, Norihiro; Murakami, Takamichi; Yeo, Winnie; Seong, Jinsil; Jia, Ji-Dong; Han, Kwan-Hyub; Cheng, Ann-Lii

2015-01-01

A key mission of the Asia-Pacific Primary Liver Cancer Expert (APPLE) Association is to ensure a coherent view for management of hepatocellular carcinoma (HCC) and to advance new treatment for this difficult disease. At the 5th APPLE meeting, held in July 2014 in Taipei, Taiwan, an APPLE consensus development program was established to facilitate discussion among experts in the Asia-Pacific region on pertinent issues for HCC management, including (1) surgery for intermediate/advanced-stage disease, (2) prevention of HCC recurrence after curative treatment, (3) optimizing imaging diagnosis, (4) radiotherapy: current practice and future clinical trials, and (5) the role of cytotoxic chemotherapy. A pre-congress questionnaire was undertaken with the consensus development committee members to help understand the current practice patterns for HCC in the Asia-Pacific region and to identify issues relating to optimal patient care and further clinical trials for which consensus needs to be developed. In this report, the results of the questionnaire are presented, and the pertinent issues identified by each consensus group for further discussion and consensus development are summarized. PMID:26020032

Are advance directives helpful for good end of life decision making: a cross sectional survey of health professionals.

PubMed

Peicius, Eimantas; Blazeviciene, Aurelija; Kaminskas, Raimondas

2017-06-05

This paper joins the debate over changes in the role of health professionals when applying advance directives to manage the decision-making process at the end of life care. Issues in relation to advance directives occur in clinical units in Lithuania; however, it remains one of the few countries in the European Union (EU) where the discussion on advance directives is not included in the health-care policy-making agenda. To encourage the discussion of advance directives, a study was designed to examine health professionals' understanding and preferences related to advance directives. In addition, the study sought to explore the views of health care professionals of the application of Advance Directives (AD) in clinical practice in Lithuania. A cross-sectional survey was conducted by interviewing 478 health professionals based at major health care centers in Kaunas district, Lithuania. The design of the study included the use of a questionnaire developed for this study and validated by a pilot study. The collected data were analyzed using standard descriptive statistical methods. The analysis of knowledge about AD revealed some statistically significant differences when comparing the respondents' profession and gender. The analysis also indicated key emerging themes among respondents including tranquility of mind, the longest possible life expectancy and freedom of choice. Further, the study findings revealed that more than half of the study participants preferred to express their will while alive by using advance directives. The study findings revealed a low level of knowledge on advance directives among health professionals. Most health professionals agreed that AD's improved end-of-life decision making while the majority of physicians appreciated AD as the best tool for sharing responsibilities in clinical practice in Lithuania. More physicians than nurses preferred the presence of advance directives to support their decision making in end-of-life situations.

How Do Pharmacists Develop into Advanced Level Practitioners? Learning from the Experiences of Critical Care Pharmacists.

PubMed

Seneviratne, Ruth E; Bradbury, Helen; Bourne, Richard S

2017-07-07

The national UK standards for critical care highlight the need for clinical pharmacists to practise at an advanced level (equivalent to Royal Pharmaceutical Society, Great Britain, Faculty Advanced Stage II (MFRPSII)) and above. Currently the UK is unable to meet the workforce capacity requirements set out in the national standards in terms of numbers of pharmacist working at advanced level and above. The aim of this study was to identify the strategies, barriers and challenges to achieving Advanced Level Practice (ALP) by learning from the experiences of advanced level critical care pharmacists within the UK. Eight participants were recruited to complete semi-structured interviews on their views and experiences of ALP. The interviews were analysed thematically and three overarching themes were identified; support, work-based learning and reflective practice. The results of this study highlight that to increase the number of MFRPSII level practitioners within critical care support for their ALP development is required. This support involves developing face-to-face access to expert critical care pharmacists within a national training programme. Additionally, chief pharmacists need to implement drivers including in house mentorship and peer review programmes and the need to align job descriptions and appraisals to the Royal Pharmaceutical Society, Great Britain, Advanced Practice Framework (APF).

How Do Pharmacists Develop into Advanced Level Practitioners? Learning from the Experiences of Critical Care Pharmacists

PubMed Central

Seneviratne, Ruth E.; Bradbury, Helen

2017-01-01

The national UK standards for critical care highlight the need for clinical pharmacists to practise at an advanced level (equivalent to Royal Pharmaceutical Society, Great Britain, Faculty Advanced Stage II (MFRPSII)) and above. Currently the UK is unable to meet the workforce capacity requirements set out in the national standards in terms of numbers of pharmacist working at advanced level and above. The aim of this study was to identify the strategies, barriers and challenges to achieving Advanced Level Practice (ALP) by learning from the experiences of advanced level critical care pharmacists within the UK. Eight participants were recruited to complete semi-structured interviews on their views and experiences of ALP. The interviews were analysed thematically and three overarching themes were identified; support, work-based learning and reflective practice. The results of this study highlight that to increase the number of MFRPSII level practitioners within critical care support for their ALP development is required. This support involves developing face-to-face access to expert critical care pharmacists within a national training programme. Additionally, chief pharmacists need to implement drivers including in house mentorship and peer review programmes and the need to align job descriptions and appraisals to the Royal Pharmaceutical Society, Great Britain, Advanced Practice Framework (APF). PMID:28970450

The Development and Application of Airway Devices in China

PubMed Central

Chen, Xiangdong; Ma, Wuhua; Liu, Renyu; Yao, Shanglong

2017-01-01

Airway management is one of the most important tasks for anesthesiologists. Anesthesiologists are experts in airway management and have made tremendous contribution to the development of the airway devices. Chinese anesthesiologists have made significant contribution in introducing advanced airway management and developing innovative techniques and devices for airway management in China. This article overviews the development and application of airway devices in China as well as the dedication and contribution of Chinese experts in the development of novel airway devices. With the development of science and technology accompanied by the advanced knowledge in airway management, more effective and safe artificial airways will be developed for clinical practice. The authors believe that Chinese experts will continue their outstanding contribution to the development of innovative airway devices, systems and knowledge. PMID:28191485

Species Profiles: Life Histories and Environmental Requirements of Coastal Fishes and Invertebrates (Mid-Atlantic). Atlantic Marsh Fiddler.

DTIC Science & Technology

1989-09-01

strabismus and amblyopia , or developing clinical screening procedures. Used with a large monitor. VisionWorks is highly suitable for developing advanced...of vision deficits in strabismus and amblyopia . *Electrophysiological and psychophysical response to spatio-temporal and novel stimuli for

Emergency medicine in Dubai, UAE.

PubMed

Partridge, Robert; Abbo, Michael; Virk, Alamjit

2009-08-18

Dubai has rapidly risen to prominence in the Persian Gulf region as a center of global commerce and tourism and as a cultural crossroad between East and West. The health-care infrastructure has undergone rapid development. Collaborations with academic medical centers now exist to advance clinical care, teaching and research. Emergency medicine has also advanced and is undergoing dynamic change. Dubai may soon emerge as a regional leader in emergency medicine training and practice.

AACN's healthy work environment standards and an empowering nurse advancement system.

PubMed

Vollers, Dawn; Hill, Edie; Roberts, Cynthia; Dambaugh, Lori; Brenner, Zara R

2009-12-01

An empowering clinical nurse advancement system can facilitate institutional behaviors that embrace all of AACN's healthy work environment standards and thus serve as a building block for developing a flourishing health care environment. The results generate positive outcomes that are evident to health care professionals, patients, patients' families, and health care organizations. Patients benefit from highly satisfied employees who work in a culture of caring and excellence.

Deriving consensus on the characteristics of advanced practice nursing: meta-summary of more than 2 decades of research.

PubMed

Hutchinson, Marie; East, Leah; Stasa, Helen; Jackson, Debra

2014-01-01

Over recent decades, there has been considerable research and debate about essential features of advanced nursing practice and differences among various categories of advanced practice nurses. This study aimed to derive an integrative description of the defining characteristics of advanced practice nursing through a meta-summary of the existing literature. A three-phase approach involved (a) systematic review of the literature to identify the specific activities characterized as advanced practice nursing, (b) qualitative meta-summary of practice characteristics extracted from manuscripts meeting inclusion criteria; and (c) statistical analysis of domains across advanced practice categories and country in which the study was completed. A descriptive framework was distilled using qualitative and quantitative results. Fifty manuscripts met inclusion criteria and were retained for analysis. Seven domains of advanced nursing practice were identified: (a) autonomous or nurse-led extended clinical practice; (b) improving systems of care; (c) developing the practice of others; (d) developing/delivering educational programs/activities; (e) nursing research/scholarship; (f) leadership external to the organization; and (g) administering programs, budgets, and personnel. Domains were similar across categories of advanced nursing practice; the domain of developing/delivering educational programs/activities was more common in Australia than in the United States or United Kingdom. Similarity at the domain level was sufficient to suggest that advanced practice role categories are less distinct than often argued. There is merit in adopting a more integrated and consistent interpretation of advanced practice nursing.

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.

Pharmacological interventions to improve cognition and adaptive functioning in Down syndrome: Strides to date.

PubMed

Hart, Sarah J; Visootsak, Jeannie; Tamburri, Paul; Phuong, Patrick; Baumer, Nicole; Hernandez, Maria-Clemencia; Skotko, Brian G; Ochoa-Lubinoff, Cesar; Liogier D'Ardhuy, Xavier; Kishnani, Priya S; Spiridigliozzi, Gail A

2017-11-01

Although an increasing number of clinical trials have been developed for cognition in Down syndrome, there has been limited success to date in identifying effective interventions. This review describes the progression from pre-clinical studies with mouse models to human clinical trials research using pharmacological interventions to improve cognition and adaptive functioning in Down syndrome. We also provide considerations for investigators when conducting human clinical trials and describe strategies for the pharmaceutical industry to advance the field in drug discovery for Down syndrome. Future research focusing on earlier pharmaceutical interventions, development of appropriate outcome measures, and greater collaboration between industry, academia, advocacy, and regulatory groups will be important for addressing limitations from prior studies and developing potential effective interventions for cognition in Down syndrome. © 2017 Wiley Periodicals, Inc.

Development of a pediatric palliative care team.

PubMed

Ward-Smith, Peggy; Linn, Jill Burris; Korphage, Rebecca M; Christenson, Kathy; Hutto, C J; Hubble, Christopher L

2007-01-01

The American Academy of Pediatrics has provided clinical recommendations for palliative care needs of children. This article outlines the steps involved in implementing a pediatric palliative care program in a Midwest pediatric magnet health care facility. The development of a Pediatric Advanced Comfort Care Team was supported by hospital administration and funded through grants. Challenges included the development of collaborative relationships with health care professionals from specialty areas. Pediatric Advanced Comfort Care Team services, available from the time of diagnosis, are provided by a multidisciplinary team of health care professionals and individualized on the basis of needs expressed by each child and his or her family.

Current stage in inflammatory bowel disease: What is next?

PubMed Central

Gómez-Gómez, Gonzalo Jesús; Masedo, Ángeles; Yela, Carmen; Martínez-Montiel, Maria del Pilar; Casís, Begoña

2015-01-01

In recent years, the incidence of inflammatory bowel disease (IBD) has been on the rise, extending to countries where it was infrequent in the past. As a result, the gap between high and low incidence countries is decreasing. The disease, therefore, has an important economic impact on the healthcare system. Advances in recent years in pharmacogenetics and clinical pharmacology have allowed for the development of treatment strategies adjusted to the patient profile. Concurrently, new drugs aimed at inflammatory targets have been developed that may expand future treatment options. This review examines advances in the optimization of existing drug treatments and the development of novel treatment options for IBD. PMID:26525013

Antiretroviral therapy: current drugs.

PubMed

Pau, Alice K; George, Jomy M

2014-09-01

The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date. Published by Elsevier Inc.

Recent developments in photodetection for medical applications

NASA Astrophysics Data System (ADS)

Llosá, Gabriela

2015-07-01

The use of the most advanced technology in medical imaging results in the development of high performance detectors that can significantly improve the performance of the medical devices employed in hospitals. Scintillator crystals coupled to photodetectors remain to be essential detectors in terms of performance and cost for medical imaging applications in different imaging modalities. Recent advances in photodetectors result in an increase of the performance of the medical scanners. Solid state detectors can provide substantial performance improvement, but are more complex to integrate into clinical detectors due mainly to their higher cost. Solid state photodetectors (APDs, SiPMs) have made new detector concepts possible and have led to improvements in different imaging modalities. Recent advances in detectors for medical imaging are revised.

How can a competency framework for advanced practice support care?

PubMed

Stanford, Pamela Elizabeth

2016-11-10

Aim To explore whether perception of nurse practitioners in relation to whether a competency framework for advanced practice can support their work. Method A qualitative cross-sectional design was used, embedded in an interpretative paradigm of research. A non-probability sample of eight experienced nurse practitioners took part in focus groups and answered questionnaires. A mixture of phenomenological and grounded theory approaches were used to collect the data. Findings Four major themes were identified: competency frameworks can identify individual strengths and weaknesses, they can be used to set clear goals and targets, they can improve how practice is organised, and they have the potential to limit practice in terms of narrowing boundaries. The study also found competency frameworks could provide an structure to guide the development and evaluation of educational programmes. Conclusion Competency frameworks can be used so to target the development of new advanced nurse practitioners. They can address workforce development and governance by ensuring nurse practitioners have the competencies to provide safe, autonomous practice. Competency frameworks have been shown to ensure consistency in clinical practice skills underpinned with nurse practitioners' theoretical knowledge. They provide a clear development structure for career development and advanced practice. However, internationally, there is still a lack of definition of advanced practice and its core competencies.

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.

Recent technological advances in computed tomography and the clinical impact therein.

PubMed

Runge, Val M; Marquez, Herman; Andreisek, Gustav; Valavanis, Anton; Alkadhi, Hatem

2015-02-01

Current technological advances in CT, specifically those with a major impact on clinical imaging, are discussed. The intent was to provide for both medical physicists and practicing radiologists a summary of the clinical impact of each advance, offering guidance in terms of utility and day-to-day clinical implementation, with specific attention to radiation dose reduction.

Natural orifice translumenal endoscopic surgery: Progress in humans since white paper

PubMed Central

Santos, Byron F; Hungness, Eric S

2011-01-01

Since the first description of the concept of natural orifice translumenal endoscopic surgery (NOTES), a substantial number of clinical NOTES reports have appeared in the literature. This editorial reviews the available human data addressing research questions originally proposed by the white paper, including determining the optimal method of access for NOTES, developing safe methods of lumenal closure, suturing and anastomotic devices, advanced multitasking platforms, addressing the risk of infection, managing complications, addressing challenges with visualization, and training for NOTES procedures. An analysis of the literature reveals that so far transvaginal access and closure appear to be the most feasible techniques for NOTES, with a limited, but growing transgastric, transrectal, and transesophageal NOTES experience in humans. The theoretically increased risk of infection as a result of NOTES procedures has not been substantiated in transvaginal and transgastric procedures so far. Development of suturing and anastomotic devices and advanced platforms for NOTES has progressed slowly, with limited clinical data on their use so far. Data on the optimal management and incidence of intraoperative complications remain sparse, although possible factors contributing to complications are discussed. Finally, this editorial discusses the likely direction of future NOTES development and its possible role in clinical practice. PMID:21483624

Teaching Commercial Law in the Third Year: A Short Report on a Business Organizations and Commercial Law Clinic.

ERIC Educational Resources Information Center

Dolan, John F.; McNair, Russell A., Jr.

1995-01-01

The development and implementation of a clinic to offer advanced study in business organizations and commercial law transactions for third-year law students at Wayne State University (Michigan) are described. The course builds vertically on prior study and puts students in contact with practicing lawyers in an academic setting. Considerations…

Accelerating Pediatric Cancer Drug Development: Challenges and Opportunities for Pediatric Master Protocols.

PubMed

Khan, Tahira; Stewart, Mark; Blackman, Samuel; Rousseau, Raphaël; Donoghue, Martha; Cohen, Kenneth; Seibel, Nita; Fleury, Mark; Benettaib, Bouchra; Malik, Raleigh; Vassal, Gilles; Reaman, Gregory

2018-01-01

Although outcomes for children with cancer have significantly improved over the past 40 years, there has been little progress in the treatment of some pediatric cancers, particularly when advanced. Additionally, clinical trial options and availability are often insufficient. Improved genomic and immunologic understanding of pediatric cancers, combined with innovative clinical trial designs, may provide an enhanced opportunity to study childhood cancers. Master protocols, which incorporate the use of precision medicine approaches, coupled with the ability to quickly assess the safety and effectiveness of new therapies, have the potential to accelerate early-phase clinical testing of novel therapeutics and which may result in more rapid approval of new drugs for children with cancer. Designing and conducting master protocols for children requires addressing similar principles and requirements as traditional adult oncology trials, but there are also unique considerations for master protocols conducted in children with cancer. The purpose of this paper is to define the key challenges and opportunities associated with this approach in order to ensure that master protocols can be adapted to benefit children and adolescents and ensure that adequate data are captured to advance, in parallel, the clinical development of investigational agents for children with cancer.

Frontiers of monoclonal antibodies: Applications in medical practices.

PubMed

Ghagane, Shridhar C; Puranik, Sridevi I; Gan, Siew Hua; Hiremath, Murigendra B; Nerli, R B; Ravishankar, M V

2017-01-01

With the flourishing of innovation in drug discovery into a new era of personalized therapy, the use of monoclonal antibodies (mAbs) in the treatment of various ailments lies at the forefront. Major improvements in genetic sequencing and biomedical techniques as well as research into mAbs emphasize on determining new targets for advanced therapy while maximizing efficacy for clinical application. However, a balance has to be achieved concerning developing a target with low toxicity combined with high specificity and versatility, to allow a specific antibody to facilitate several biotic effects, ranging from neutralization of virus mechanisms to modulation of immune response and maintaining low global economic cost. Presently, there are approximately 30 mAbs' permitted for therapeutic use with many more being tested in clinical trials. Nevertheless, the heavy cost of mAbs' production, stowage and management as well as the subsequent hindrances to their development are outweighed by mAbs' clinical advantages. Compared to conventional drugs, since mAbs use as pharmacologic iotas have specific physical features and modes of action, they should be considered as a discrete therapeutic category. In this review, the history of mAb generation and the innovative technological applications of mAbs that has advanced in clinical practices is reviewed.

Cell based advanced therapeutic medicinal products for bone repair: Keep it simple?

PubMed

Leijten, J; Chai, Y C; Papantoniou, I; Geris, L; Schrooten, J; Luyten, F P

2015-04-01

The development of cell based advanced therapeutic medicinal products (ATMPs) for bone repair has been expected to revolutionize the health care system for the clinical treatment of bone defects. Despite this great promise, the clinical outcomes of the few cell based ATMPs that have been translated into clinical treatments have been far from impressive. In part, the clinical outcomes have been hampered because of the simplicity of the first wave of products. In response the field has set-out and amassed a plethora of complexities to alleviate the simplicity induced limitations. Many of these potential second wave products have remained "stuck" in the development pipeline. This is due to a number of reasons including the lack of a regulatory framework that has been evolving in the last years and the shortage of enabling technologies for industrial manufacturing to deal with these novel complexities. In this review, we reflect on the current ATMPs and give special attention to novel approaches that are able to provide complexity to ATMPs in a straightforward manner. Moreover, we discuss the potential tools able to produce or predict 'goldilocks' ATMPs, which are neither too simple nor too complex. Copyright © 2014 Elsevier B.V. All rights reserved.

Interprofessional Obstetric Ultrasound Education: Successful Development of Online Learning Modules; Case-Based Seminars; and Skills Labs for Registered and Advanced Practice Nurses, Midwives, Physicians, and Trainees.

PubMed

Shaw-Battista, Jenna; Young-Lin, Nichole; Bearman, Sage; Dau, Kim; Vargas, Juan

2015-01-01

Ultrasound is an important aid in the clinical diagnosis and management of normal and complicated pregnancy and childbirth. The technology is widely applied to maternity care in the United States, where comprehensive standard ultrasound examinations are routine. Targeted scans are common and used for an increasing number of clinical indications due to emerging research and a greater availability of equipment with better image resolution at lower cost. These factors contribute to an increased demand for obstetric ultrasound education among students and providers of maternity care, despite a paucity of data to inform education program design and evaluation. To meet this demand, from 2012 to 2015 the University of California, San Francisco nurse-midwifery education program developed and implemented an interprofessional obstetric ultrasound course focused on clinical applications commonly managed by maternity care providers from different professions and disciplines. The course included matriculating students in nursing and medicine, as well as licensed practitioners such as registered and advanced practice nurses, midwives, and physicians and residents in obstetrics and gynecology and family medicine. After completing 10 online modules with a pre- and posttest of knowledge and interprofessional competencies related to teamwork and communication, trainees attended a case-based seminar and hands-on skills practicum with pregnant volunteers. The course aimed to establish a foundation for further supervised clinical training prior to independent practice of obstetric ultrasound. Course development was informed by professional guidelines and clinical and education research literature. This article describes the foundations, with a review of the challenges and solutions encountered in obstetric ultrasound education development and implementation. Our experience will inform educators who wish to facilitate obstetric ultrasound competency development among new and experienced maternity care providers in academic and clinical settings. This article is part of a special series of articles that address midwifery innovations in clinical practice, education, interprofessional collaboration, health policy, and global health. © 2015 by the American College of Nurse-Midwives.

The Bridging Advanced Developments for Exceptional Rehabilitation (BADER) Consortium: Reaching in Partnership for Optimal Orthopaedic Rehabilitation Outcomes

PubMed Central

Stanhope, Steven J.; Wilken, Jason M.; Pruziner, Alison L.; Dearth, Christopher L.; Wyatt, Marilynn; Ziemke, CAPT Gregg W.; Strickland, Rachel; Milbourne, Suzanne A.; Kaufman, Kenton R.

2017-01-01

The Bridging Advanced Developments for Exceptional Rehabilitation (BADER) Consortium began in September 2011 as a cooperative agreement with the Department of Defense (DoD) Congressionally Directed Medical Research Programs Peer Reviewed Orthopaedic Research Program. A partnership was formed with DoD Military Treatment Facilities (MTFs), U.S. Department of Veterans Affairs (VA) Centers, the National Institutes of Health (NIH), academia, and industry to rapidly conduct innovative, high-impact, and sustainable clinically relevant research. The BADER Consortium has a unique research capacity-building focus that creates infrastructures and strategically connects and supports research teams to conduct multiteam research initiatives primarily led by MTF and VA investigators. BADER relies on strong partnerships with these agencies to strengthen and support orthopaedic rehabilitation research. Its focus is on the rapid forming and execution of projects focused on obtaining optimal functional outcomes for patients with limb loss and limb injuries. The Consortium is based on an NIH research capacity-building model that comprises essential research support components that are anchored by a set of BADER-funded and initiative-launching studies. Through a partnership with the DoD/VA Extremity Trauma and Amputation Center of Excellence, the BADER Consortium’s research initiative-launching program has directly supported the identification and establishment of eight BADER-funded clinical studies. BADER’s Clinical Research Core (CRC) staff, who are embedded within each of the MTFs, have supported an additional 37 non-BADER Consortium-funded projects. Additional key research support infrastructures that expedite the process for conducting multisite clinical trials include an omnibus Cooperative Research and Development Agreement and the NIH Clinical Trials Database. A 2015 Defense Health Board report highlighted the Consortium’s vital role, stating the research capabilities of the DoD Advanced Rehabilitation Centers are significantly enhanced and facilitated by the BADER Consortium. PMID:27849456

The Bridging Advanced Developments for Exceptional Rehabilitation (BADER) Consortium: Reaching in Partnership for Optimal Orthopaedic Rehabilitation Outcomes.

PubMed

Stanhope, Steven J; Wilken, Jason M; Pruziner, Alison L; Dearth, Christopher L; Wyatt, Marilynn; Ziemke, Gregg W; Strickland, Rachel; Milbourne, Suzanne A; Kaufman, Kenton R

2016-11-01

The Bridging Advanced Developments for Exceptional Rehabilitation (BADER) Consortium began in September 2011 as a cooperative agreement with the Department of Defense (DoD) Congressionally Directed Medical Research Programs Peer Reviewed Orthopaedic Research Program. A partnership was formed with DoD Military Treatment Facilities (MTFs), U.S. Department of Veterans Affairs (VA) Centers, the National Institutes of Health (NIH), academia, and industry to rapidly conduct innovative, high-impact, and sustainable clinically relevant research. The BADER Consortium has a unique research capacity-building focus that creates infrastructures and strategically connects and supports research teams to conduct multiteam research initiatives primarily led by MTF and VA investigators.BADER relies on strong partnerships with these agencies to strengthen and support orthopaedic rehabilitation research. Its focus is on the rapid forming and execution of projects focused on obtaining optimal functional outcomes for patients with limb loss and limb injuries. The Consortium is based on an NIH research capacity-building model that comprises essential research support components that are anchored by a set of BADER-funded and initiative-launching studies. Through a partnership with the DoD/VA Extremity Trauma and Amputation Center of Excellence, the BADER Consortium's research initiative-launching program has directly supported the identification and establishment of eight BADER-funded clinical studies. BADER's Clinical Research Core (CRC) staff, who are embedded within each of the MTFs, have supported an additional 37 non-BADER Consortium-funded projects. Additional key research support infrastructures that expedite the process for conducting multisite clinical trials include an omnibus Cooperative Research and Development Agreement and the NIH Clinical Trials Database. A 2015 Defense Health Board report highlighted the Consortium's vital role, stating the research capabilities of the DoD Advanced Rehabilitation Centers are significantly enhanced and facilitated by the BADER Consortium. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

MO-C-BRB-04: Observations of a Nuclear Radiologist on the Value of the Medical Physicist

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

Greenspan, B.

With the profound changes currently occurring in medicine, the role of the medical physicist cannot stagnate, but must evolve to meet the challenges and opportunities that are presented. Medical physicists must understand these changes and establish themselves not only as relevant but as leaders in this new environment. We must increase our presence in clinical settings such as tumor boards, patient rounds, and the development of new diagnosis, imaging, and treatment techniques. By establishing ourselves as competent scientists, we can and must participate in the development of technologies through research, teaching, and clinical implementation. As medical physicists we must definemore » our roles and value to our physician colleagues, patients, referring physicians, and senior administrators. We cannot afford to be viewed solely as quality assurance technologists, but need to move forward in step with medical and practice advances, becoming recognized as having a leadership role in providing quality research, technological development, and quality patient care. In this session, four leaders in medical research and healthcare will discuss their observations on how medical physicists have contributed to advancements in healthcare and opportunities to continue leadership in providing quality medicine through the applications of physics to research, education, and clinical practice. Learning Objectives: Understand the changes in the healthcare environment and how medical physicists can contribute to improving patient care. Learn how medical physicists are currently leading research efforts to improve clinical imaging and diagnosis. Understand the role of medical physicists in developing new technology and leading its translation into clinical care.« less

MO-C-BRB-02: The Physicists’ Leadership Role in Academic Radiology: The Chair’s Perspective

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

Arenson, R.

With the profound changes currently occurring in medicine, the role of the medical physicist cannot stagnate, but must evolve to meet the challenges and opportunities that are presented. Medical physicists must understand these changes and establish themselves not only as relevant but as leaders in this new environment. We must increase our presence in clinical settings such as tumor boards, patient rounds, and the development of new diagnosis, imaging, and treatment techniques. By establishing ourselves as competent scientists, we can and must participate in the development of technologies through research, teaching, and clinical implementation. As medical physicists we must definemore » our roles and value to our physician colleagues, patients, referring physicians, and senior administrators. We cannot afford to be viewed solely as quality assurance technologists, but need to move forward in step with medical and practice advances, becoming recognized as having a leadership role in providing quality research, technological development, and quality patient care. In this session, four leaders in medical research and healthcare will discuss their observations on how medical physicists have contributed to advancements in healthcare and opportunities to continue leadership in providing quality medicine through the applications of physics to research, education, and clinical practice. Learning Objectives: Understand the changes in the healthcare environment and how medical physicists can contribute to improving patient care. Learn how medical physicists are currently leading research efforts to improve clinical imaging and diagnosis. Understand the role of medical physicists in developing new technology and leading its translation into clinical care.« less

Drugs in development for Parkinson's disease: an update.

PubMed

Johnston, Tom H; Brotchie, Jonathan M

2006-01-01

The current development of emerging pharmacological treatments for Parkinson's disease (PD), front preclinical to launch, is summarized. Advances over the past year are highlighted, including the significant progress of several drugs through various stages of development. Several agents have been discontinued from development, either because of adverse effects or lack of clinical efficacy. The methyl-esterified form of L-DOPA (melevodopa) and the monoamine oxidase type B inhibitor rasagiline have both been launched. With regard to the monoamine re-uptake inhibitors, many changes have been witnessed, with new agents reaching preclinical development and pre-existing ones being discontinued or having no development reported. Of the dopamine agonists, many continue to progress successfully through clinical trials. Others have struggled to demonstrate a significant advantage over currently available treatments and have been discontinued. The field of non-dopaminergic treatments remains dynamic. The alpha2 adrenergic receptor antagonists and the adenosine A2A receptor antagonists remain in clinical trials. Trials of the neuronal' synchronization modulator levetiracetam are at an advanced stage, and there has also been a new addition to the class (ie, seletracetam). There has been a change in the landscape of neuroprotective agents that modulate disease progression. Candidates from the classes of growth factors and glyceraldehyde-3-phosphate dehydrogenase inhibitors have been discontinued, or no development has been reported, and the mixed lineage kinase inhibitor CEP-1347 has been discontinued for PD treatment. Other drugs in this field, such as neuroimmunophilins, estrogens and alpha-synuclein oligomerization inhibitors, remain in development.

Translating stem cell therapies: the role of companion animals in regenerative medicine

PubMed Central

Volk, Susan W.; Theoret, Christine

2013-01-01

Veterinarians and veterinary medicine have been integral to the development of stem cell therapies. The contributions of large animal experimental models to the development and refinement of modern hematopoietic stem cell transplantation were noted nearly five decades ago. More recent advances in adult stem cell/regenerative cell therapies continue to expand knowledge of the basic biology and clinical applications of stem cells. A relatively liberal legal and ethical regulation of stem cell research in veterinary medicine has facilitated the development and in some instances clinical translation of a variety of cell-based therapies involving hematopoietic (HSC) and mesenchymal stem cells (MSC) as well as other adult regenerative cells and recently embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC). In fact, many of the pioneering developments in these fields of stem cell research have been achieved through collaborations of veterinary and human scientists. This review aims to provide an overview of the contribution of large animal veterinary models in advancing stem cell therapies for both human and clinical veterinary applications. Moreover, in the context of the “One Health Initiative”, the role veterinary patients may play in the future evolution of stem cell therapies for both human and animal patients will be explored. PMID:23627495

Regulatory considerations for clinical development of cancer vaccines.

PubMed

Heelan, Bridget Theresa

2014-01-01

Cancer vaccines are aimed at stimulating an immune response to tumor tissue. There is a high level of clinical activity in this rapidly advancing field with over 1,400 trials registered on Clincaltrials.gov. The recent approval of Sipuleucel-T which is the first cancer vaccine approved in the US and EU has encouraged developers in this field. In contrast to more established approaches for treating cancer such as chemotherapy, regulatory guidelines have been developed relatively recently for cancer vaccines. These guidelines advise on general clinical requirements. As there is an increase in innovative strategies with novel products, a 2-way dialog with regulators is recommended on a case-by-case basis to justify the clinical development plan, taking into account specific quality issues related to the product(s) in development. It is important that the rationale, background and justification for the planned development is convincing when interacting with the regulatory authorities, to enable drug developers and regulators to reach agreement.

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.

Clinical Pharmacology & Therapeutics: Past, Present and Future

PubMed Central

Waldman, SA; Terzic, A

2016-01-01

Clinical Pharmacology & Therapeutics (CPT), the definitive and timely source for advances in human therapeutics, transcends the drug discovery, development, regulation and utilization continuum to catalyze, evolve and disseminate discipline-transformative knowledge. Prioritized themes and multidisciplinary content drive the science and practice of clinical pharmacology, offering a trusted point of reference. An authoritative herald across global communities, CPT is a timeless information vehicle at the vanguard of discovery, translation and application ushering therapeutic innovation into modern health care. PMID:28194770

ACTS Satellite Telemammography Network Experiments

NASA Technical Reports Server (NTRS)

Kachmar, Brian A.; Kerczewski, Robert J.

2000-01-01

The Satellite Networks and Architectures Branch of NASA's Glenn Research Center has developed and demonstrated several advanced satellite communications technologies through the Advanced Communications Technology Satellite (ACTS) program. One of these technologies is the implementation of a Satellite Telemammography Network (STN) encompassing NASA Glenn, the Cleveland Clinic Foundation. the University of Virginia, and the Ashtabula County Medical Center. This paper will present a look at the STN from its beginnings to the impact it may have on future telemedicine applications. Results obtained using the experimental ACTS satellite demonstrate the feasibility of Satellite Telemammography. These results have improved teleradiology processes and mammography image manipulation, and enabled advances in remote screening methodologies. Future implementation of satellite telemammography using next generation commercial satellite networks will be explored. In addition, the technical aspects of the project will be discussed, in particular how the project has evolved from using NASA developed hardware and software to commercial off the shelf (COTS) products. Development of asymmetrical link technologies was an outcome of this work. Improvements in the display of digital mammographic images, better understanding of end-to-end system requirements, and advances in radiological image compression were achieved as a result of the research. Finally, rigorous clinical medical studies are required for new technologies such as digital satellite telemammography to gain acceptance in the medical establishment. These experiments produced data that were useful in two key medical studies that addressed the diagnostic accuracy of compressed satellite transmitted digital mammography images. The results of these studies will also be discussed.

Robotic Surgical Training in an Academic Institution

PubMed Central

Chitwood, W. Randolph; Nifong, L. Wiley; Chapman, William H. H.; Felger, Jason E.; Bailey, B. Marcus; Ballint, Tara; Mendleson, Kim G.; Kim, Victor B.; Young, James A.; Albrecht, Robert A.

2001-01-01

Objective To detail robotic procedure development and clinical applications for mitral valve, biliary, and gastric reflux operations, and to implement a multispecialty robotic surgery training curriculum for both surgeons and surgical teams. Summary Background Data Remote, accurate telemanipulation of intracavitary instruments by general and cardiac surgeons is now possible. Complex technologic advancements in surgical robotics require well-designed training programs. Moreover, efficient robotic surgical procedures must be developed methodically and safely implemented clinically. Methods Advanced training on robotic systems provides surgeon confidence when operating in tiny intracavitary spaces. Three-dimensional vision and articulated instrument control are essential. The authors’ two da Vinci robotic systems have been dedicated to procedure development, clinical surgery, and training of surgical specialists. Their center has been the first United States site to train surgeons formally in clinical robotics. Results Established surgeons and residents have been trained using a defined robotic surgical educational curriculum. Also, 30 multispecialty teams have been trained in robotic mechanics and electronics. Initially, robotic procedures were developed experimentally and are described. In the past year the authors have performed 52 robotic-assisted clinical operations: 18 mitral valve repairs, 20 cholecystectomies, and 14 Nissen fundoplications. These respective operations required 108, 28, and 73 minutes of robotic telemanipulation to complete. Procedure times for the last half of the abdominal operations decreased significantly, as did the knot-tying time in mitral operations. There have been no deaths and few complications. One mitral patient had postoperative bleeding. Conclusion Robotic surgery can be performed safely with excellent results. The authors have developed an effective curriculum for training teams in robotic surgery. After training, surgeons have applied these methods effectively and safely. PMID:11573041

Understanding the components of publication success: a survey of academic award recipients.

PubMed

Kenny, Anne M; Rowland, Heather; Gruman, Cynthia A

2003-04-01

This study examines predictors of publication number in career development awardees. We examined whether daily writing predicted publication number among junior faculty. We surveyed 94 career development awardees; the survey consisted of 28 questions in four domains: characteristics, environment, writing practices, and attitudes about writing. Variables that contributed positively to publication number included male gender and those with a negative effect were clinical research and perceiving the need to write as a requirement for advancement. In subgroup analysis of junior faculty, a habit of writing daily was predictive of greater publication numbers. Career development awardees published more first-authored manuscripts if they were male, were involved in nonclinical research, and did not perceive writing as a requirement for advancement. These factors highlight the need to explore the lower overall publication productivity in women and in clinical investigators. Junior faculty members that write daily publish more manuscripts, regardless of gender, research type, or motivators. The benefits of daily writing warrant direct study if not empiric implementation.

Addressing Gaps in Mental Health and Addictions Nursing Leadership: An Innovative Professional Development Initiative.

PubMed

Gehrs, Margaret; Strudwick, Gillian; Ling, Sara; Reisdorfer, Emilene; Cleverley, Kristin

2017-01-01

Mental health and addictions services are integral to Canada's healthcare system, and yet it is difficult to recruit experienced nurse leaders with advanced practice, management or clinical informatics expertise in this field. Master's-level graduates, aspiring to be mental health nurse leaders, often lack the confidence and experience required to lead quality improvement, advancements in clinical care, service design and technology innovations for improved patient care. This paper describes an initiative that develops nursing leaders through a unique scholarship, internship and mentorship model, which aims to foster confidence, critical thinking and leadership competency development in the mental health and addictions context. The "Mutual Benefits Model" framework was applied in the design and evaluation of the initiative. It outlines how mentee, mentor and organizational needs can drive strategic planning of resource investment, mentorship networks and relevant leadership competency-based learning plans to optimize outcomes. Five-year individual and organizational outcomes are described. © 2017 Longwoods Publishing.

A Longitudinal Emergency Medical Services Track in Emergency Medicine Residency.

PubMed

Adams, Daniel; Bischof, Jason; Larrimore, Ashley; Krebs, William; King, Andrew

2017-03-30

Emergency medicine residency programs offer Emergency Medical Services (EMS) curricula to address Accreditation Council for Graduate Medical Education (ACGME) milestones. While some programs offer advanced clinical tracks in EMS, no standard curriculum exists. We sought to establish a well-defined EMS curriculum to allow interested residents to develop advanced clinical skills and scholarship within this subspecialty. Core EMS fellowship trained faculty were recruited to help develop the curriculum. Building on ACGME graduation requirements and milestones, important elements of EMS fellowship training were incorporated into the curriculum to develop the final document. The final curriculum focuses on scholarly activities relating to the four core areas of EMS identified by The American Board of Emergency Medicine and serves as an intermediary between ACGME graduation requirements for education in EMS and fellowship level training. Standardization of the EMS scholarly track can provide residents with the potential to obtain competency beyond ACGME requirements and prepare them for success in fellowship training and/or leadership within EMS on graduation.

A Longitudinal Emergency Medical Services Track in Emergency Medicine Residency

PubMed Central

Bischof, Jason; Larrimore, Ashley; Krebs, William; King, Andrew

2017-01-01

Emergency medicine residency programs offer Emergency Medical Services (EMS) curricula to address Accreditation Council for Graduate Medical Education (ACGME) milestones. While some programs offer advanced clinical tracks in EMS, no standard curriculum exists. We sought to establish a well-defined EMS curriculum to allow interested residents to develop advanced clinical skills and scholarship within this subspecialty. Core EMS fellowship trained faculty were recruited to help develop the curriculum. Building on ACGME graduation requirements and milestones, important elements of EMS fellowship training were incorporated into the curriculum to develop the final document. The final curriculum focuses on scholarly activities relating to the four core areas of EMS identified by The American Board of Emergency Medicine and serves as an intermediary between ACGME graduation requirements for education in EMS and fellowship level training. Standardization of the EMS scholarly track can provide residents with the potential to obtain competency beyond ACGME requirements and prepare them for success in fellowship training and/or leadership within EMS on graduation. PMID:28465874

Big data to smart data in Alzheimer's disease: The brain health modeling initiative to foster actionable knowledge.

PubMed

Geerts, Hugo; Dacks, Penny A; Devanarayan, Viswanath; Haas, Magali; Khachaturian, Zaven S; Gordon, Mark Forrest; Maudsley, Stuart; Romero, Klaus; Stephenson, Diane

2016-09-01

Massive investment and technological advances in the collection of extensive and longitudinal information on thousands of Alzheimer patients results in large amounts of data. These "big-data" databases can potentially advance CNS research and drug development. However, although necessary, they are not sufficient, and we posit that they must be matched with analytical methods that go beyond retrospective data-driven associations with various clinical phenotypes. Although these empirically derived associations can generate novel and useful hypotheses, they need to be organically integrated in a quantitative understanding of the pathology that can be actionable for drug discovery and development. We argue that mechanism-based modeling and simulation approaches, where existing domain knowledge is formally integrated using complexity science and quantitative systems pharmacology can be combined with data-driven analytics to generate predictive actionable knowledge for drug discovery programs, target validation, and optimization of clinical development. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Cross-boundary rotational working for neonatal nurses.

PubMed

Kane, Tina

2007-05-01

Neonatal services in England and Wales are undergoing significant changes as a result of technological advances as well as the development of new networks. These changes have had a dramatic effect on the neonatal workforce. The skills of the available staff govern the level of activity of neonatal units: many units have had to re-evaluate the services they can safely deliver with the available workforce. This has resulted in the re-configuration of some neonatal units and changes in the dependency levels of many. Units have had to undertake reviews of the patterns of working of their staff to ensure that a skilled and competent workforce is available to provide the level of care each neonatal service requires. Shortages in some areas have meant that units have had to find new ways to retain and update skilled staff. This article describes a rotational programme developed with the aim of providing a continued clinical development pathway for neonatal nursing staff. The programme incorporates competency assessments of emergency skills and clinical and technological advances in neonatal care.

[Recent Advances and Prospect of Advanced Non-small Cell Lung Cancer Targeted 
Therapy: Focus on Small Molecular Tyrosine Kinase Inhibitors].

PubMed

Zhang, Guowei; Wang, Huijuan; Ma, Zhiyong

2017-04-20

At present the treatment of advanced non-small cell lung cancer enters a targeted era and develops rapidly. New drugs appear constantly. Small molecular tyrosine kinase inhibitors have occupied the biggest piece of the territory, which commonly have a clear biomarker as predictor, and show remarkable effect in specific molecular classification of patients. The epidermal growth factor tyrosine kinase inhibitors such as gefitinib, erlotinib, icotinib and anaplastic lymphoma kinase tyrosine kinase inhibitors crizotinib have brought a milestone advance. In recent years new generations of tyrosine kinase inhibitors have achieved a great success in patients with acquired resistance to the above two kinds of drugs. At the same time new therapeutic targets are constantly emerging. So in this paper, we reviewed and summarized the important drugs and clinical trails on this topic, and made a prospect of the future development.

Statin use and the incidence of advanced age-related macular degeneration in the Complications of Age-related Macular Degeneration Prevention Trial.

PubMed

Maguire, Maureen G; Ying, Gui-shuang; McCannel, Colin A; Liu, Chengcheng; Dai, Yang

2009-12-01

To evaluate the impact of statin use on the incidence of advanced age-related macular degeneration (AMD) and its components, choroidal neovascularization (CNV) and geographic atrophy (GA), among patients with bilateral large drusen. Cohort study within a multicenter, randomized, clinical trial. Patients enrolled in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). Eligibility criteria for the clinical trial required that participants have >or=10 large (>125 microm) drusen and visual acuity >or=20/40 in each eye. Patients scheduled for their final CAPT visit after May 2005 were interviewed on their history of use of cholesterol-lowering medications, including statins. Trained readers identified CNV and end point GA (>1 Macular Photocoagulation Study disc area of GA) based on review of fluorescein angiograms and fundus photographs taken at annual follow-up visits and when patients reported symptoms. The risk ratio for participants developing CNV or developing GA associated with statin use was estimated with time-dependent Cox proportional hazards models. Development of advanced AMD, CNV, and end point GA. Among 764 patients eligible for the interview, 744 (97.4%) patients completed the interview on medication use. Statin use was reported by 296 (39.8%) of those interviewed, with the majority, 187 (63.2%) of the 296, beginning use after enrollment in CAPT. Among 744 patients, advanced AMD developed in 332 (22.5%) eyes of 242 (32.5%) patients, CNV in 222 (15%) eyes of 176 (23.7%) patients, and GA in 114 (7.7%) eyes of 80 (10.8%) patients. With adjustment for other risk factors, the estimated risk ratio for eyes (95% confidence interval) associated with statin use was 1.15 (0.87-1.52) for advanced AMD, 1.35 (0.99-1.83) for CNV, and 0.80 (0.46-1.39) for GA. The CAPT data are not consistent with a strong protective effect (risk ratio,

A biomarker panel for non-alcoholic steatohepatitis (NASH) and NASH-related fibrosis.

PubMed

Younossi, Zobair M; Page, Sandra; Rafiq, Nila; Birerdinc, Aybike; Stepanova, Maria; Hossain, Noreen; Afendy, Arian; Younoszai, Zahra; Goodman, Zachary; Baranova, Ancha

2011-04-01

Patients with biopsy-proven NASH and especially those with fibrosis are at risk for progressive liver disease, emphasizing the clinical importance of developing non-invasive biomarkers for NASH and NASH-related fibrosis. This study examines the performance of a new biomarker panel for NASH and NASH-related fibrosis with a combination of clinical and laboratory variables. Enrolled patients had biopsy-proven NAFLD. Clinical data, laboratory data, and serum samples were collected at the time of biopsy. Fasting serum was assayed for adiponectin, resistin, glucose, M30, M65, Tissue inhibitor of metalloproteinases-1 (Timp-1), ProCollagen 3 N-terminal peptide (PIIINP), and hyaluronic acid (HA). Regression models predictive of NASH, NASH-related fibrosis, and NASH-related advanced fibrosis were designed and cross-validated. Of the 79 enrolled NAFLD patients, 40 had biopsy-proven NASH and 39 had non-NASH NAFLD. Clinical and laboratory data were from this cohort were used to develop a NAFLD Diagnostic Panel that includes three models (models for NASH, NASH-related fibrosis, and NASH-related advanced fibrosis). The model for predicting NASH includes diabetes, gender, BMI, triglycerides, M30 (apoptosis), and M65-M30 (necrosis) [AUC: 0.81, 95% CI, 0.70-0.89, 300 p value <9E 301 (-06)]. The NASH-related fibrosis prediction model includes the same predictors [AUC: 0.80, 95% CI 0.68-0.88, 307 p value <0.00014]. Finally, the NASH-related advanced fibrosis model includes type 2 diabetes, serum triglycerides, Timp-1, and AST [AUC: 0.81, 95% CI, 0.70-0.89; p value, 0.000062]. This NAFLD Diagnostic Panel based on a clinical and laboratory data has good performance characteristics and is easy to use. This biomarker panel could become useful in the management of patients with NAFLD.

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 and metastatic lesions. Regarding the assessment of response to cancer therapy, the liquid biopsy is not ready to replace medical imaging, but adds critical new information; for instance, through a temporal assessment of quantitative circulating tumor DNA (ctDNA) assay results, and importantly, the ability to monitor for signs of resistance, via emerging clones. Adjuvant therapy may soon be considered based on a quantitative cfDNA assay. As sensitivity and specificity of the technology continue to progress, cancer screening and prevention will improve and save countless lives by finding the cancer early, so that a routine surgery may be all that is required for a definitive cure.

Long-term effects of vitamins C and E, β-carotene, and zinc on age-related macular degeneration: AREDS report no. 35.

PubMed

Chew, Emily Y; Clemons, Traci E; Agrón, Elvira; Sperduto, Robert D; Sangiovanni, John Paul; Kurinij, Natalie; Davis, Matthew D

2013-08-01

To describe the long-term effects (10 years) of the Age-Related Eye Disease Study (AREDS) formulation of high-dose antioxidants and zinc supplement on progression of age-related macular degeneration (AMD). Multicenter, randomized, controlled, clinical trial followed by an epidemiologic follow-up study. We enrolled 4757 participants with varying severity of AMD in the clinical trial; 3549 surviving participants consented to the follow-up study. Participants were randomly assigned to antioxidants C, E, and β-carotene and/or zinc versus placebo during the clinical trial. For participants with intermediate or advanced AMD in 1 eye, the AREDS formulation delayed the progression to advanced AMD. Participants were then enrolled in a follow-up study. Eye examinations were conducted with annual fundus photographs and best-corrected visual acuity assessments. Medical histories and mortality were obtained for safety monitoring. Repeated measures logistic regression was used in the primary analyses. Photographic assessment of progression to, or history of treatment for, advanced AMD (neovascular [NV] or central geographic atrophy [CGA]), and moderate visual acuity loss from baseline (≥15 letters). Comparison of the participants originally assigned to placebo in AREDS categories 3 and 4 at baseline with those originally assigned to AREDS formulation at 10 years demonstrated a significant (P<0.001) odds reduction in the risk of developing advanced AMD or the development of NV AMD (odds ratio [OR], 0.66, 95% confidence interval [CI], 0.53-0.83 and OR, 0.60; 95% CI, 0.47-0. 78, respectively). No significant reduction (P = 0.93) was seen for the CGA (OR, 1.02; 95% CI, 0.71-1.45). A significant reduction (P = 0.002) for the development of moderate vision loss was seen (OR 0.71; 95% CI, 0.57-0.88). No adverse effects were associated with the AREDS formulation. Mortality was reduced in participants assigned to zinc, especially death from circulatory diseases. Five years after the clinical trial ended, the beneficial effects of the AREDS formulation persisted for development of NV AMD but not for CGA. These results are consistent with the original recommendations that persons with intermediate or advanced AMD in 1 eye should consider taking the AREDS formulation. The authors have no proprietary or commercial interest in any of the materials discussed in this article. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Recent advances in the prenatal interrogation of the human fetal genome.

PubMed

Hui, Lisa; Bianchi, Diana W

2013-02-01

The amount of genetic and genomic information obtainable from the human fetus during pregnancy is accelerating at an unprecedented rate. Two themes have dominated recent technological advances in prenatal diagnosis: interrogation of the fetal genome in increasingly high resolution and the development of non-invasive methods of fetal testing using cell-free DNA in maternal plasma. These two areas of advancement have now converged with several recent reports of non-invasive assessment of the entire fetal genome from maternal blood. However, technological progress is outpacing the ability of the healthcare providers and patients to incorporate these new tests into existing clinical care, and further complicates many of the economic and ethical dilemmas in prenatal diagnosis. This review summarizes recent work in this field and discusses the integration of these new technologies into the clinic and society. Copyright © 2012 Elsevier Ltd. All rights reserved.

Genetic engineering for skeletal regenerative medicine.

PubMed

Gersbach, Charles A; Phillips, Jennifer E; García, Andrés J

2007-01-01

The clinical challenges of skeletal regenerative medicine have motivated significant advances in cellular and tissue engineering in recent years. In particular, advances in molecular biology have provided the tools necessary for the design of gene-based strategies for skeletal tissue repair. Consequently, genetic engineering has emerged as a promising method to address the need for sustained and robust cellular differentiation and extracellular matrix production. As a result, gene therapy has been established as a conventional approach to enhance cellular activities for skeletal tissue repair. Recent literature clearly demonstrates that genetic engineering is a principal factor in constructing effective methods for tissue engineering approaches to bone, cartilage, and connective tissue regeneration. This review highlights this literature, including advances in the development of efficacious gene carriers, novel cell sources, successful delivery strategies, and optimal target genes. The current status of the field and the challenges impeding the clinical realization of these approaches are also discussed.

The consultant nurse - expert practitioner and much more.

PubMed

Mitchell, Theresa; Butler-Williams, Carole; Easton, Karen; Ingledew, Ian; Parkin, Donna; Wade, Sharon; Warner, Richard

The consultant nurse (CN) role is usually described in terms of four domains devised by the Department of Health - clinical practice, education and training, leadership, and research and service development. This study set out to explicate the diversity and complexity of CN roles in an NHS trust; to describe aspects of extraordinary practice and to identify perceived differences between this role and other advanced practice roles. Accounts were written by six CNs and subjected to concept mapping to facilitate identification of extraordinary practice. Four themes emerged: entrepreneurial activity and innovation; clinical autonomy and role dynamism; influential national and international research conduct; consultancy and education across discipline boundaries. These included descriptions of higher order skills that surpass usual requirements of 'expert' or 'advanced' practice. Comparisons with other advanced practice roles are drawn from the literature and data collected in this study. Differences between the roles have implications for sustainability.

Recent developments in genetics and medically assisted reproduction: from research to clinical applications.

PubMed

Harper, J C; Aittomäki, K; Borry, P; Cornel, M C; de Wert, G; Dondorp, W; Geraedts, J; Gianaroli, L; Ketterson, K; Liebaers, I; Lundin, K; Mertes, H; Morris, M; Pennings, G; Sermon, K; Spits, C; Soini, S; van Montfoort, A P A; Veiga, A; Vermeesch, J R; Viville, S; Macek, M

2018-01-01

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.

Five important advances in hematopathology.

PubMed

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

2014-03-01

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

Writing an employer-focused resume for advanced practice nurses.

PubMed

Welton, Robert H

2013-01-01

The most important new trend in resumes is the employer-focused resume. Writing one is not difficult, but it requires a change in focus. The focus of this type of resume is on the needs of prospective employers. This new resume format allows applicants to describe to prospective employers what they can provide related to the employer's needs as opposed to a simple listing of their academic and work experiences without relation to the prospective new job. This article provides advanced practice nurses with sources to guide construction of informative text about their advanced practice nursing skills and competencies using language familiar to employers. Resumes and curriculum vitae formats are compared, and advice is provided on developing content for either format. Guidelines are provided about listing credentials, identifying clinical proficiencies from student clinical practicum, using qualification summaries rather than an objective statement, choosing references, and including essential components in a cover letter.

Advancing nursing enterprises: A cross-country comparison.

PubMed

Pittman, Patricia; Salmon, Marla E

2016-01-01

Health system transformations in the United States are creating new opportunities for nursing innovation, although financial sustainability has limited the expansion of nurse managed clinics. We explore case studies of nursing enterprises in the developing world and discuss their potential for informing related work in the United States. Cases were selected from the Center for Health Market Innovations. We describe a professional association network of clinics in Tanzania, a social franchise in Kenya, and a cooperative in the Philippines. All programs empowered nurses to own, lead, and advance their professional influence. They had a social mission of improving access to care for disadvantaged populations, while increasing employment and autonomy of women. They also provided a shared platform for branding, purchasing, and quality assurance. Organization sponsors in these models may be relevant to different actors in the United States. Each demonstrates the importance of a collective approach to advancing nursing enterprises. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Pharmacogenetics in clinical practice: how far have we come and where are we going?

PubMed Central

Johnson, Julie A

2013-01-01

Recent years have seen great advances in our understanding of genetic contributors to drug response. Drug discovery and development around targeted genetic (somatic) mutations has led to a number of new drugs with genetic indications, particularly for the treatment of cancers. Our knowledge of genetic contributors to variable drug response for existing drugs has also expanded dramatically, such that the evidence now supports clinical use of genetic data to guide treatment in some situations, and across a variety of therapeutic areas. Clinical implementation of pharmacogenetics has seen substantial growth in recent years and groups are working to identify the barriers and best practices for pharmacogenetic-guided treatment. The advances and challenges in these areas are described and predictions about future use of genetics in drug therapy are discussed. PMID:23651030

The target invites a foe: antibody-drug conjugates in gynecologic oncology.

PubMed

Campos, Maira P; Konecny, Gottfried E

2018-02-01

Antibody-drug conjugates (ADCs) represent a promising new class of cancer therapeutics. Currently more than 60 ADCs are in clinical development, however, only very few trials focus on gynecologic malignancies. In this review, we summarize the most recent advances in ADC drug development with an emphasis on how this progress relates to patients diagnosed with gynecologic malignancies and breast cancer. The cytotoxic payloads of the majority of the ADCs that are currently in clinical trials for gynecologic malignancies or breast cancer are auristatins (MMAE, MMAF), maytansinoids (DM1, DM4), calicheamicin, pyrrolobenzodiazepines and SN-38. Both cleavable and noncleavable linkers are currently being investigated in clinical trials. A number of novel target antigens are currently being validated in ongoing clinical trials including folate receptor alpha, mesothelin, CA-125, NaPi2b, NOTCH3, protein tyrosine kinase-like 7, ephrin-A4, TROP2, CEACAM5, and LAMP1. For most ADCs currently in clinical development, dose-limiting toxicities appear to be unrelated to the targeted antigen but more tightly associated with the payload. Rational drug design involving optimization of the antibody, the linker and the conjugation chemistry is aimed at improving the therapeutic index of new ADCs. Antibody-drug conjugates can increase the efficacy and decrease the toxicity of their payloads in comparison with traditional cyctotoxic agents. A better and quicker translation of recent scientific advances in the field of ADCs into rational clinical trials for patients diagnosed with ovarian, endometrial or cervical cancer could create real improvements in tumor response, survival and quality of life for our patients.

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

Application of Biomarkers in the Development of Drugs Intended for the Treatment of Osteoarthritis

PubMed Central

Kraus, Virginia Byers; Burnett, Bruce; Coindreau, Javier; Cottrell, Susan; Eyre, David; Gendreau, Michael; Gardiner, Jennifer; Garnero, Patrick; Hardin, John; Henrotin, Yves; Heinegård, Dick; Ko, Amy; Lohmander, Stefan; Matthews, Gloria; Menetski, Joseph; Moskowitz, Roland; Persiani, Stefano; Poole, Robin; Rousseau, Jean Charles; Todman, Martin

2013-01-01

Objective Osteoarthritis (OA) is a chronic and slowly progressive disease for which biomarkers may be able to provide a more rapid indication of therapeutic responses to therapy than is currently available; this could accelerate and facilitate OA drug discovery and development programs. The goal of this document is to provide a summary and guide to the application of in vitro (biochemical and other soluble) biomarkers in the development of drugs for OA and to outline and stimulate a research agenda that will further this goal. Methods The Biomarkers Working Group representing experts in the field of OA biomarker research from both academia and industry developed this consensus document between 2007–2009 at the behest of the Osteoarthritis Research Society International (OARSI FDA initiative). Results This document summarizes definitions and classification systems for biomarkers, the current outcome measures used in OA clinical trials, applications and potential utility of biomarkers for development of OA therapeutics, the current state of qualification of OA-related biomarkers, pathways for biomarker qualification, critical needs to advance the use of biomarkers for drug development, recommendations regarding practices and clinical trials, and a research agenda to advance the science of OA-related biomarkers. Conclusions Although many OA-related biomarkers are currently available they exist in various states of qualification and validation. The biomarkers that are likely to have the earliest beneficial impact on clinical trials fall into two general categories, those that will allow targeting of subjects most likely to either respond and/or progress (prognostic value) within a reasonable and manageable time frame for a clinical study (for instance within one to two years for an OA trial), and those that provide early feedback for preclinical decision-making and for trial organizers that a drug is having the desired biochemical effect. As in vitro biomarkers are increasingly investigated in the context of specific drug treatments, advances in the field can be expected that will lead to rapid expansion of the list of available biomarkers with increasing understanding of the molecular processes that they represent. PMID:21396468

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 waiting to be "translated" into useful therapies and diagnostics. In addition to highlighting the major research advances over the past year, this report also identifies key barriers to accelerating the pace of cancer research and outlines ASCO's recommendations for overcoming them. Despite these and other challenges, there is much good news on the front lines of cancer research. This report demonstrates the essential role of clinical cancer research in finding new and better ways to treat, diagnose, and prevent a group of diseases that strike half of men and one-third of women in the United States.

New Insights in the Clinical Understanding of Behçet's Disease

PubMed Central

Cho, Sung Bin; Cho, Suhyun

2012-01-01

Behçet's disease is a chronic relapsing multisystemic inflammatory disorder characterized by four major symptoms (oral aphthous ulcers, genital ulcers, skin lesions, and ocular lesions) and occasionally by five minor symptoms (arthritis, gastrointestinal ulcers, epididymitis, vascular lesions, and central nervous system symptoms). Although the etiology of Behçet's disease is still unknown, there have been recent advances in immunopathogenic studies, genome-wide association studies, animal models, diagnostic markers, and new biological agents. These advances have improved the clinical understanding of Behçet's disease and have enabled us to develop new treatment strategies for this intractable disease, which remains one of the leading causes of blindness. PMID:22187230

An eye for discovery

PubMed Central

Stahl, Andreas; Smith, Lois E.H.

2010-01-01

Vision research has often led to significant advances in our understanding of biology. There has also been particular success in translating basic research in the eye into breakthrough clinical therapies that mark important milestones for ophthalmology and also for medical research. Anti-VEGF therapy for age-related macular degeneration was named as one of the top ten science advancements of the year 2006. Only two years later, successful transfer of the RPE65 gene into retinal pigment epithelium of patients with Leber congenital amaurosis was noted as one of the most important clinical applications of gene therapy. The articles in this Review series outline current developments in vision research and highlight its continued importance in ophthalmology and medicine. PMID:20811156

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 nurse specialist role changes and the acute care nurse practitioner role emerges, it is imperative that advanced practice nurses describe their contribution to health care. Associating advanced practice nursing activities with outcomes will help further characterize these 2 advanced practice roles.

Association for medical education and research in substance abuse.

PubMed

Samet, Jeffrey H; Galanter, Marc; Bridden, Carly; Lewis, David C

2006-01-01

The Association for Medical Education and Research in Substance Abuse (AMERSA) is a multi-disciplinary organization committed to health professional faculty development in substance abuse. In 1976, members of the Career Teachers Training Program in Alcohol and Drug Abuse, a US federally funded multi-disciplinary faculty development program, formed AMERSA. The organization grew from 59 founding members, who were primarily medical school faculty, to over 300 health professionals from a spectrum of disciplines including physicians, nurses, social workers, dentists, allied health professionals, psychologists and other clinical educators who are responsible for advancing substance abuse education. AMERSA members promote substance abuse education among health professionals by developing curricula, promulgating relevant policy and training health professional faculty to become excellent teachers in this field. AMERSA influences public policy by offering standards for improving substance abuse education. The organization publishes a peer-reviewed, quarterly journal, Substance Abuse, which emphasizes research on the education and training of health professions and also includes original clinical and prevention research. Each year, the AMERSA National Conference brings together researchers and health professional educators to learn about scientific advances and exemplary teaching approaches. In the future, AMERSA will continue to pursue this mission of advancing and supporting health professional faculty who educate students and trainees to address substance abuse in patients and clients.

Development of ipilimumab: contribution to a new paradigm for cancer immunotherapy.

PubMed

Hoos, Axel; Ibrahim, Ramy; Korman, Alan; Abdallah, Kald; Berman, David; Shahabi, Vafa; Chin, Kevin; Canetta, Renzo; Humphrey, Rachel

2010-10-01

Identification of cytotoxic T-lymphocyte antigen-4 (CTLA-4) as a key negative regulator of T-cell activity led to development of the fully human, monoclonal antibody ipilimumab to block CTLA-4 and potentiate antitumor T-cell responses. Animal studies first provided insight into the ability of an anti-CTLA-4 antibody to cause tumor regression, particularly in combination regimens. Early clinical studies defined ipilimumab pharmacokinetics and possibilities for combinability. Phase II trials of ipilimumab in advanced melanoma showed objective responses, but a greater number of patients had disease stabilization. In a phase III trial, ipilimumab was the first agent to demonstrate an improvement in overall survival in patients with previously treated, advanced melanoma. The adverse event profile associated with ipilimumab was primarily immune-related. Adverse events can be severe and life-threatening, but most were reversible using treatment guidelines. Ipilimumab monotherapy exhibits conventional and new patterns of activity in advanced melanoma, with a delayed separation of Kaplan-Meier survival curves. The observation of some new response patterns with ipilimumab, which are not captured by standard response criteria, led to novel criteria for the evaluation of immunotherapy in solid tumors. Overall, lessons from the development of ipilimumab contributed to a new clinical paradigm for cancer immunotherapy evolved by the Cancer Immunotherapy Consortium. Copyright © 2010 Elsevier Inc. All rights reserved.

Recent Advances and Perspectives in Cancer Drug Design.

PubMed

Magalhaes, Luma G; Ferreira, Leonardo L G; Andricopulo, Adriano D

2018-01-01

Cancer is one of the leading causes of death worldwide. With the increase in life expectancy, the number of cancer cases has reached unprecedented levels. In this scenario, the pharmaceutical industry has made significant investments in this therapeutic area. Despite these efforts, cancer drug research remains a remarkably challenging field, and therapeutic innovations have not yet achieved expected clinical results. However, the physiopathology of the disease is now better understood, and the discovery of novel molecular targets has refreshed the expectations of developing improved treatments. Several noteworthy advances have been made, among which the development of targeted therapies is the most significant. Monoclonal antibodies and antibody-small molecule conjugates have emerged as a worthwhile approach to improve drug selectivity and reduce adverse effects, which are the main challenges in cancer drug discovery. This review will examine the current panorama of drug research and development (R&D) with emphasis on some of the major advances brought to clinical trials and to the market in the past five years. Breakthrough discoveries will be highlighted along with the medicinal chemistry strategies used throughout the discovery process. In addition, this review will provide perspectives and updates on the discovery of novel molecular targets as well as drugs with innovative mechanisms of action.

The role of intracochlear drug delivery devices in the management of inner ear disease.

PubMed

Ayoob, Andrew M; Borenstein, Jeffrey T

2015-03-01

Diseases of the inner ear include those of the auditory and vestibular systems, and frequently result in disabling hearing loss or vertigo. Despite a rapidly expanding pipeline of potential cochlear therapeutics, the inner ear remains a challenging organ for targeted drug delivery, and new technologies are required to deliver these therapies in a safe and efficacious manner. In addition to traditional approaches for direct inner ear drug delivery, novel microfluidics-based systems are under development, promising improved control over pharmacokinetics over longer periods of delivery, ultimately with application towards hair cell regeneration in humans. Advances in the development of intracochlear drug delivery systems are reviewed, including passive systems, active microfluidic technologies and cochlear prosthesis-mediated delivery. This article provides a description of novel delivery systems and their potential future clinical applications in treating inner ear disease. Recent progresses in microfluidics and miniaturization technologies are enabling the development of wearable and ultimately implantable drug delivery microsystems. Progress in this field is being spurred by the convergence of advances in molecular biology, microfluidic flow control systems and models for drug transport in the inner ear. These advances will herald a new generation of devices, with near-term applications in preclinical models, and ultimately with human clinical use for a range of diseases of the inner ear.

Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors and Non-Small Cell Lung Cancer (NSCLC) - Advances in Molecular Diagnostic Techniques to Facilitate Targeted Therapy.

PubMed

Ghafoor, Qamar; Baijal, Shobhit; Taniere, Phillipe; O'Sullivan, Brendan; Evans, Matthew; Middleton, Gary

2017-12-21

A subset of patients with non-small cell lung cancer (NSCLC) respond well to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), due to the presence of sensitising mutations in the gene encoding EGFR. Mutations associated with resistance to first generation EGFR TKIs have also been identified, which lead to therapeutic failure and the requirement for new drugs. Three generations of EGFR TKIs have been developed and either have been, or are being, evaluated as first and/or second line therapeutic agents. In this review, we consider the advances in molecular diagnostic techniques that are used, or are in development, to facilitate the targeted EGFR TKI therapy of patients with NSCLC. A literature search was conducted in May 2017 using PubMed, and spanning the period September 2005 (EU approval date of erlotinib) to May 2017. Search terms used were: EGFR TKI, NSCLC, clinical trial, erlotinib, gefitinib, afatinib, EGFR mutations, Exon 19 deletion, and Leu858Arg. The use of molecular data, in conjunction with other clinical and diagnostic information, will assist physicians to make the best therapeutic choice for each patient with advanced NSCLC. Personalized medicine and a rapidly developing therapy landscape will enable these patients to achieve optimal responses to EGFR TKIs.

Material aid for vaccines

NASA Astrophysics Data System (ADS)

Irvine, Darrell

2018-06-01

Darrell Irvine provides an overview of the recent advances in materials science that have enabled the use of innovative natural and synthetic compounds in vaccine development capable of regulating the potency and safety of new vaccines progressing towards the clinic.

Extreme-Scale Computing Project Aims to Advance Precision Oncology | FNLCR Staging

Cancer.gov

Two government agencies and five national laboratories are collaborating to develop extremely high-performance computing capabilities that will analyze mountains of research and clinical data to improve scientific understanding of cancer, predict dru

Quality in restorative dentistry: a report of an advanced postgraduate dental symposium.

PubMed

Wilson, N H

1996-08-01

A joint Royal College of Surgeons of Edinburgh--Royal College of Physicians and Surgeons of Glasgow Advanced Postgraduate Dental Symposium addressed the issue of quality in restorative dentistry. The overall view was that quality in clinical care, including all aspects of restorative dentistry, is the consistent achievement of successful outcome. Ongoing developments and effective audit processes were recognized to provide important opportunities for continuous quality improvement in restorative dentistry.

Severe cutaneous toxicity following treatment with radiotherapy and cetuximab: a case report

PubMed Central

2009-01-01

While the addition of cetuximab to radiotherapy improves clinical outcomes in locoregionally advanced head and neck squamous cell cancers, there are a small number of reports of severe radiation dermatitis occurring with this therapeutic combination. We present the case of a 69 year old male who developed severe radiation dermatitis following treatment with cetuximab and radiotherapy for a locoregionally advanced head and neck squamous cell cancer. PMID:19128507

Recent advances in diagnostic microbiology.

PubMed

Bravo, Lulette Tricia C; Procop, Gary W

2009-07-01

The past decade has seen a surge in the development of a variety of molecular diagnostics designed to rapidly identify or characterize medically important microorganisms. We briefly review important advances in molecular microbiology, and then discuss specific assays that have been implemented in clinical microbiology laboratories throughout the country. We also discuss emerging methods and technologies that will soon be more widely used for the prompt and accurate detection of the agents of infectious diseases.

Advancing pig cloning technologies towards application in regenerative medicine.

PubMed

Nagashima, H; Matsunari, H; Nakano, K; Watanabe, M; Umeyama, K; Nagaya, M

2012-08-01

Regenerative medicine is expected to make a significant contribution by development of novel therapeutic treatments for intractable diseases and for improving the quality of life of patients. Many advances in regenerative medicine, including basic and translational research, have been developed and tested in experimental animals; pigs have played an important role in various aspects of this work. The value of pigs as a model species is being enhanced by the generation of specially designed animals through cloning and genetic modifications, enabling more sophisticated research to be performed and thus accelerating the clinical application of regenerative medicine. This article reviews the significant aspects of the creation and application of cloned and genetically modified pigs in regenerative medicine research and considers the possible future directions of the technology. We also discuss the importance of reproductive biology as an interface between basic science and clinical medicine. © 2012 Blackwell Verlag GmbH.

Recent neuroimaging, neurophysiological, and neuropathological advances for the understanding of NPC

PubMed Central

Benussi, Alberto; Cotelli, Maria Sofia; Padovani, Alessandro; Borroni, Barbara

2018-01-01

Niemann–Pick disease type C (NPC) is a rare autosomal recessive lysosomal storage disorder with extensive biological, molecular, and clinical heterogeneity. Recently, numerous studies have tried to shed light on the pathophysiology of the disease, highlighting possible disease pathways common to other neurodegenerative disorders, such as Alzheimer’s disease and frontotemporal dementia, and identifying possible candidate biomarkers for disease staging and response to treatment. Miglustat, which reversibly inhibits glycosphingolipid synthesis, has been licensed in the European Union and elsewhere for the treatment of NPC in both children and adults. A number of ongoing clinical trials might hold promise for the development of new treatments for NPC. The objective of the present work is to review and evaluate recent literature data in order to highlight the latest neuroimaging, neurophysiological, and neuropathological advances for the understanding of NPC pathophysiology. Furthermore, ongoing developments in disease-modifying treatments will be briefly discussed. PMID:29511534

Recent advances in therapeutic recruitment of mammalian RNAi and bacterial CRISPR-Cas DNA interference pathways as emerging antiviral strategies.

PubMed

Chin, Wei-Xin; Ang, Swee Kim; Chu, Justin Jang Hann

2017-01-01

In invertebrate eukaryotes and prokaryotes, respectively, the RNAi and clustered regularly interspaced short palindromic repeats-CRISPR-associated (CRISPR-Cas) pathways are highly specific and efficient RNA and DNA interference systems, and are well characterised as potent antiviral systems. It has become possible to recruit or reconstitute these pathways in mammalian cells, where they can be directed against desired host or viral targets. The RNAi and CRISPR-Cas systems can therefore yield ideal antiviral therapeutics, capable of specific and efficient viral inhibition with minimal off-target effects, but development of such therapeutics can be slow. This review covers recent advances made towards developing RNAi or CRISPR-Cas strategies for clinical use. These studies address the delivery, toxicity or target design issues that typically plague the in vivo or clinical use of these technologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

New therapeutic approaches to spinal muscular atrophy.

PubMed

Lewelt, Aga; Newcomb, Tara M; Swoboda, Kathryn J

2012-02-01

Bench to bedside progress has been widely anticipated for a growing number of neurodegenerative disorders. Of these, spinal muscular atrophy (SMA) is perhaps the best poised to capitalize on advances in targeted therapeutics development over the next few years. Several laboratories have achieved compelling success in SMA animal models using sophisticated methods for targeted delivery, repair, or increased expression of the survival motor neuron protein, SMN. The clinical community is actively collaborating to identify, develop, and validate outcome measures and biomarkers in parallel with laboratory efforts. Innovative trial design and synergistic approaches to maximize proactive care in conjunction with treatment with one or more of the promising pharmacologic and biologic therapies currently in the pipeline will maximize our chances to achieve meaningful outcomes for patients. This review highlights recent promising scientific and clinical advances bringing us ever closer to effective treatment(s) for our patients with SMA.

Advancing Diagnostics to Address Antibacterial Resistance: The Diagnostics and Devices Committee of the Antibacterial Resistance Leadership Group

PubMed Central

Tsalik, Ephraim L.; Petzold, Elizabeth; Kreiswirth, Barry N.; Bonomo, Robert A.; Banerjee, Ritu; Lautenbach, Ebbing; Evans, Scott R.; Hanson, Kimberly E.; Klausner, Jeffrey D.

2017-01-01

Abstract Diagnostics are a cornerstone of the practice of infectious diseases. However, various limitations frequently lead to unmet clinical needs. In most other domains, diagnostics focus on narrowly defined questions, provide readily interpretable answers, and use true gold standards for development. In contrast, infectious diseases diagnostics must contend with scores of potential pathogens, dozens of clinical syndromes, emerging pathogens, rapid evolution of existing pathogens and their associated resistance mechanisms, and the absence of gold standards in many situations. In spite of these challenges, the importance and value of diagnostics cannot be underestimated. Therefore, the Antibacterial Resistance Leadership Group has identified diagnostics as 1 of 4 major areas of emphasis. Herein, we provide an overview of that development, highlighting several examples where innovation in study design, content, and execution is advancing the field of infectious diseases diagnostics. PMID:28350903

Immunotherapy for Head and Neck Squamous Cell Carcinoma: A Review of Current and Emerging Therapeutic Options

PubMed Central

Moskovitz, Jessica M.; Moy, Jennifer; Seiwert, Tanguy Y.

2017-01-01

Abstract Advances in the field of cancer immunotherapy have occurred rapidly over the past decade. Exciting results from clinical trials have led to new treatment options and improved survival for patients with a myriad of solid tumor pathologies. However, questions remain unanswered regarding duration and timing of therapy, combination regimens, appropriate biomarkers of disease, and optimal monitoring of therapeutic response. This article reviews emerging immunotherapeutic agents and significant clinical trials that have led to advancements in the field of immuno‐oncology for patients with head and neck squamous cell carcinoma. Implications for Practice. This review article summarizes recently developed agents that harness the immune system to fight head and neck squamous cell carcinoma. A brief review of the immune system and its role in cancer development is included. Recently completed and emerging therapeutic trials centering on the immune system and head and neck cancer are reviewed. PMID:28507203

Cardiac gene therapy: Recent advances and future directions.

PubMed

Mason, Daniel; Chen, Yu-Zhe; Krishnan, Harini Venkata; Sant, Shilpa

2015-10-10

Gene therapy has the potential to serve as an adaptable platform technology for treating various diseases. Cardiovascular disease is a major cause of mortality in the developed world and genetic modification is steadily becoming a more plausible method to repair and regenerate heart tissue. Recently, new gene targets to treat cardiovascular disease have been identified and developed into therapies that have shown promise in animal models. Some of these therapies have advanced to clinical testing. Despite these recent successes, several barriers must be overcome for gene therapy to become a widely used treatment of cardiovascular diseases. In this review, we evaluate specific genetic targets that can be exploited to treat cardiovascular diseases, list the important delivery barriers for the gene carriers, assess the most promising methods of delivering the genetic information, and discuss the current status of clinical trials involving gene therapies targeted to the heart. Copyright © 2015 Elsevier B.V. All rights reserved.

Challenges faced in long term ventricular assist device support.

PubMed

Ikegami, Hirohisa; Kurlansky, Paul; Takeda, Koji; Naka, Yoshifumi

2016-08-01

The development of ventricular assist device (VAD) has been one of the revolutionary advancements in end-stage heart failure management. Although the device has developed and improved significantly over the last few decades, we still face multiple challenges. This review will discuss quality of life, survival, and clinically encountered complications in patients with VAD support. The literature was extensively reviewed for studies describing the above topic area. We describe the impact of major challenges faced in VAD support and discuss their future and expectations. Expert commentary: The technological advancement of VADs has contributed to major improvement of overall survival, enhancement of quality of life and decrease of incidence of complications. It is expected that technologies will continue to evolve. At the same time, the indications for and timing of device implantation, and selection of device type are continuously important in clinical practice setting.

Consolidation of molecular testing in clinical virology.

PubMed

Scagnolari, Carolina; Turriziani, Ombretta; Monteleone, Katia; Pierangeli, Alessandra; Antonelli, Guido

2017-04-01

The development of quantitative methods for the detection of viral nucleic acids have significantly improved our ability to manage disease progression and to assess the efficacy of antiviral treatment. Moreover, major advances in molecular technologies during the last decade have allowed the identification of new host genetic markers associated with antiviral drug response but have also strongly revolutionized the way we see and perform virus diagnostics in the coming years. Areas covered: In this review, we describe the history and development of virology diagnostic methods, dedicating particular emphasis on the gradual evolution and recent advances toward the introduction of multiparametric platforms for the syndromic diagnosis. In parallel, we outline the consolidation of viral genome quantification practice in different clinical settings. Expert commentary: More rapid, accurate and affordable molecular technology can be predictable with particular emphasis on emerging techniques (next generation sequencing, digital PCR, point of care testing and syndromic diagnosis) to simplify viral diagnosis in the next future.

Advances in Gamma-Ray Imaging with Intensified Quantum-Imaging Detectors

NASA Astrophysics Data System (ADS)

Han, Ling

Nuclear medicine, an important branch of modern medical imaging, is an essential tool for both diagnosis and treatment of disease. As the fundamental element of nuclear medicine imaging, the gamma camera is able to detect gamma-ray photons emitted by radiotracers injected into a patient and form an image of the radiotracer distribution, reflecting biological functions of organs or tissues. Recently, an intensified CCD/CMOS-based quantum detector, called iQID, was developed in the Center for Gamma-Ray Imaging. Originally designed as a novel type of gamma camera, iQID demonstrated ultra-high spatial resolution (< 100 micron) and many other advantages over traditional gamma cameras. This work focuses on advancing this conceptually-proven gamma-ray imaging technology to make it ready for both preclinical and clinical applications. To start with, a Monte Carlo simulation of the key light-intensification device, i.e. the image intensifier, was developed, which revealed the dominating factor(s) that limit energy resolution performance of the iQID cameras. For preclinical imaging applications, a previously-developed iQID-based single-photon-emission computed-tomography (SPECT) system, called FastSPECT III, was fully advanced in terms of data acquisition software, system sensitivity and effective FOV by developing and adopting a new photon-counting algorithm, thicker columnar scintillation detectors, and system calibration method. Originally designed for mouse brain imaging, the system is now able to provide full-body mouse imaging with sub-350-micron spatial resolution. To further advance the iQID technology to include clinical imaging applications, a novel large-area iQID gamma camera, called LA-iQID, was developed from concept to prototype. Sub-mm system resolution in an effective FOV of 188 mm x 188 mm has been achieved. The camera architecture, system components, design and integration, data acquisition, camera calibration, and performance evaluation are presented in this work. Mounted on a castered counter-weighted clinical cart, the camera also features portable and mobile capabilities for easy handling and on-site applications at remote locations where hospital facilities are not available.

Perspective: Integrating research into surgical residency education: lessons learned from orthopaedic surgery.

PubMed

Atesok, Kivanc I; Hurwitz, Shepard R; Egol, Kenneth A; Ahn, Jaimo; Owens, Brett D; Crosby, Lynn A; Pellegrini, Vincent D

2012-05-01

Orthopaedic research has advanced tremendously in parallel with accelerated progress in medical science. Possession of a fundamental understanding of basic and clinical science has become more essential than previously for orthopaedic surgeons to be able to translate advances in research into clinical practice. The number of medical graduates with prior education in scientific research who choose to pursue careers in orthopaedic surgery is small. Therefore, it is important that a core of research education be included during residency training to ensure the continued advancement of the clinical practice of orthopaedics. The authors examine some of the challenges to a comprehensive research experience during residency, including deficient priority, inadequate institutional infrastructure, financial strain on residency budgets, restricted time, and an insufficient number of mentors to encourage and guide residents to become clinician-scientists. They also present some strategies to overcome these challenges, including development and expansion of residency programs with clinician-scientist pathways, promotion of financial sources, and enhancement of opportunities for residents to interact with mentors who can serve as role models. Successful integration of research education into residency programs will stimulate future orthopaedic surgeons to develop the critical skills to lead musculoskeletal research, comprehend related discoveries, and translate them into patient care. Lessons learned from incorporating research training within orthopaedic residency programs will have broad application across medical specialties-in both primary and subspecialty patient care.

GC/IR computer-aided identification of anaerobic bacteria

NASA Astrophysics Data System (ADS)

Ye, Hunian; Zhang, Feng S.; Yang, Hua; Li, Zhu; Ye, Song

1993-09-01

A new method was developed to identify anaerobic bacteria by using pattern recognition. The method is depended on GC / JR data. The system is intended for use as a precise rapid and reproduceable aid in the identification of unknown isolates. Key Words: Anaerobic bacteria Pattern recognition Computeraided identification GC / JR 1 . TNTRODUCTTON A major problem in the field of anaerobic bacteriology is the difficulty in accurately precisely and rapidly identifying unknown isolates. Tn the proceedings of the Third International Symposium on Rapid Methods and Automation in Microbiology C. M. Moss said: " Chromatographic analysis is a new future for clinical microbiology" . 12 years past and so far it seems that this is an idea whose time has not get come but it close. Now two major advances that have brought the technology forword in terms ofmaking it appropriate for use in the clinical laboratory can aldo be cited. One is the development and implementation of fused silica capillary columns. In contrast to packed columns and those of'' greater width these columns allow reproducible recovery of hydroxey fatty acids with the same carbon chain length. The second advance is the efficient data processing afforded by modern microcomputer systems. On the other hand the practical steps for sample preparation also are an advance in the clinical laboratory. Chromatographic Analysis means mainly of analysis of fatty acids. The most common

A Feminine Care Clinical Research Program Transforms Women's Lives.

PubMed

Tzeghai, Ghebre E; Ajayi, Funmilayo O; Miller, Kenneth W; Imbescheid, Frank; Sobel, Jack D; Farage, Miranda A

2012-12-17

Feminine hygiene products and menstruation education have transformed the lives of women throughout the world. The P&G Feminine Care Clinical Innovation Research Program has played a key role by expanding scientific knowledge as well as developing technical insights and tools for the development of feminine hygiene products. The aim has been to meet the needs of women throughout their life stages, advancing their urogenital health beyond just menstruation, as well as helping to understand the role of sex hormones in various important health issues that women face. This review article highlights key contributions and research findings in female hygiene products, urogenital health research, and method development. The clinical research team focused on utilizing the results of clinical safety studies to advance the acceptance of feminine hygiene products world-wide. Key findings include that perception of skin sensitivity is not limited to the facial area, but is also relevant to the body and the genital area. Also, they shed light on the role of estrogen in autoimmune diseases as well as premenstrual syndrome. Efforts in the method development area focused on innovative tools that are reliable, predictive of clinical trial results and capable of measuring wear comfort, genital skin health, and the impact of product use on the consumer's quality of life. A novel method, behind-the-knee (BTK) test, developed to model irritation under normal wear conditions, was the first to account for both chemical and mechanical sources of irritation. The method has been accepted by the FDA as a substitute in clinical trials in some cases, and by American Society for Testing and Materials as a global standard test method. Additional proprietary methods were developed to enhance visual grading of irritation using cross-polarized light, to measure the amount of lotion transferred from sanitary pads, and to evaluate the skin mildness. Finally, the Farage Quality of Life tool was created to measure consumer's well-being. Based on the results of this extensive clinical research and the newly developed testing methods, the changing needs of women throughout their life stages are better met.

A Feminine Care Clinical Research Program Transforms Women’s Lives

PubMed Central

Tzeghai, Ghebre E.; Ajayi, Funmilayo O.; Miller, Kenneth W.; Imbescheid, Frank; Sobel, Jack D.; Farage, Miranda A.

2015-01-01

Feminine hygiene products and menstruation education have transformed the lives of women throughout the world. The P&G Feminine Care Clinical Innovation Research Program has played a key role by expanding scientific knowledge as well as developing technical insights and tools for the development of feminine hygiene products. The aim has been to meet the needs of women throughout their life stages, advancing their urogenital health beyond just menstruation, as well as helping to understand the role of sex hormones in various important health issues that women face. This review article highlights key contributions and research findings in female hygiene products, urogenital health research, and method development. The clinical research team focused on utilizing the results of clinical safety studies to advance the acceptance of feminine hygiene products world-wide. Key findings include that perception of skin sensitivity is not limited to the facial area, but is also relevant to the body and the genital area. Also, they shed light on the role of estrogen in autoimmune diseases as well as premenstrual syndrome. Efforts in the method development area focused on innovative tools that are reliable, predictive of clinical trial results and capable of measuring wear comfort, genital skin health, and the impact of product use on the consumer’s quality of life. A novel method, behind-the-knee (BTK) test, developed to model irritation under normal wear conditions, was the first to account for both chemical and mechanical sources of irritation. The method has been accepted by the FDA as a substitute in clinical trials in some cases, and by American Society for Testing and Materials as a global standard test method. Additional proprietary methods were developed to enhance visual grading of irritation using cross-polarized light, to measure the amount of lotion transferred from sanitary pads, and to evaluate the skin mildness. Finally, the Farage Quality of Life tool was created to measure consumer’s well-being. Based on the results of this extensive clinical research and the newly developed testing methods, the changing needs of women throughout their life stages are better met. PMID:25946910

Brain metastasis in lung cancer: Building a molecular and systems-level understanding to improve outcomes.

PubMed

Ebben, Johnathan D; You, Ming

2016-09-01

Lung cancer is a clinically difficult disease with rising disease burden around the world. Unfortunately, most lung cancers present at a clinically advanced stage. Of these cancers, many also present with brain metastasis which complicates the clinical picture. This review summarizes current knowledge on the molecular basis of lung cancer brain metastases. We start from the clinical perspective, aiming to provide a clinical context for a significant problem that requires much deeper scientific investigation. We review new research governing the metastatic process, including tumor cell signaling, establishment of a receptive tumor niches in the brain and evaluate potential new therapeutic options that take advantage of these new scientific advances. Lung cancer remains the largest single cause of cancer mortality in the United States (Siegel et al., 2015). This continues to be the clinical picture despite significant advances in therapy, including the advent of targeted molecular therapies and newly adopted immunotherapies for certain subtypes of lung cancer. In the vast majority of cases, lung cancer presents as advanced disease; in many instances, this advanced disease state is intimately associated with micro and macrometastatic disease (Goldberg et al., 2015). For both non-small cell lung cancer and small cell lung cancer patients, the predominant metastatic site is the brain, with up to 68% of patients with mediastinal lymph node metastasis eventually demonstrating brain metastasis (Wang et al., 2009).The frequency (incidence) of brain metastasis is highest in lung cancers, relative to other common epithelial malignancies (Schouten et al., 2002). Other studies have attempted to predict the risk of brain metastasis in the setting of previously non-metastatic disease. One of the largest studies to do this, analyzing historical data from 1973 to 2011 using the SEER database revealed a 9% risk of patients with previously non-metastatic NSCLC developing brain metastasis over the course of their disease, while 18% of small cell lung cancer patients without previous metastasis went on to develop brain metastasis as their disease progressed (Goncalves et al., 2016).The reasons underlying this predilection for the central nervous system, as well as the recent increase in the frequency of brain metastasis identified in patients remain important questions for both clinicians and basic scientists. More than ever, the question of how brain metastasis develop and how they can be treated and managed requires the involvement of interdisciplinary teams-and more importantly-scientists who are capable of thinking like clinicians and clinicians who are capable of thinking like scientists. This review aims to present a translational perspective on brain metastasis. We will investigate the scope of the problem of brain metastasis and the current management of the metastatic disease process in lung cancer. From this clinical starting point, we will investigate the literature surrounding the molecular underpinnings of lung tumor metastasis and seek to understand the process from a biological perspective to generate new hypotheses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Human anthelminthic vaccines: Rationale and challenges.

PubMed

Hotez, Peter J; Strych, Ulrich; Lustigman, Sara; Bottazzi, Maria Elena

2016-06-24

Helminth infections are the most common afflictions of humankind, affecting almost every single person living in profound poverty. Through mass drug administration (MDA) we have seen sharp declines in the global prevalence of some helminth infections, including lymphatic filariasis, onchocerciasis, and ascariasis. However, since 1990, there has been no appreciable decrease in the global prevalence of hookworm infection, schistosomiasis, or food-borne trematodiases. Through the activities of a non-profit product development partnerships and two research institutes, a total of five human anthelmintic vaccines for hookworm infection (two) and schistosomiasis (three) have advanced from discovery through manufacture and are now in Phase 1 clinical testing. At least three additional antigens, including two for onchocerciasis and one for schistosomiasis, are also advancing through preclinical development with the intention of moving into the clinic soon. These preventive human anthelmintic vaccines could be used as stand-alone technologies administered to infants as part of the Expanded Program on Immunization (EPI), or together with anthelmintic drugs in programs linked to MDA. Significant hurdles though could hinder the advancement of these vaccines into later-stage clinical and product development and licensure. They include the absence of a major pharma partner (and the resultant access to adjuvants and industrial scale manufacturing expertise), an uncharted roadmap for how to introduce anthelmintic vaccines into appropriate health systems, uncertain global access and regulatory strategies that might need to rely on developing country vaccine manufacturers and national regulatory authorities, and the lack of innovative financing schemes. However, the public health and economic benefits of introducing these vaccines could be massive and therefore deserve international attention and support. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Use of FEV1 in Cystic Fibrosis Epidemiologic Studies and Clinical Trials: A Statistical Perspective for the Clinical Researcher

PubMed Central

Szczesniak, Rhonda; Heltshe, Sonya L.; Stanojevic, Sanja; Mayer-Hamblett, Nicole

2017-01-01

Background Forced expiratory volume in 1 second (FEV1) is an established marker of cystic fibrosis (CF) disease progression that is used to capture clinical course and evaluate therapeutic efficacy. The research community has established FEV1 surveillance data through a variety of observational data sources such as patient registries, and there is a growing pipeline of new CF therapies demonstrated to be efficacious in clinical trials by establishing improvements in FEV1. Results In this review, we summarize from a statistical perspective the clinical relevance of FEV1 based on its association with morbidity and mortality in CF, its role in epidemiologic studies of disease progression and comparative effectiveness, and its utility in clinical trials. In addition, we identify opportunities to advance epidemiologic research and the clinical development pipeline through further statistical considerations. Conclusions Our understanding of CF disease course, therapeutics, and clinical care has evolved immensely in the past decades, in large part due to the thoughtful application of rigorous research methods and meaningful clinical endpoints such as FEV1. A continued commitment to conduct research that minimizes the potential for bias, maximizes the limited patient population, and harmonizes approaches to FEV1 analysis while maintaining clinical relevance, will facilitate further opportunities to advance CF care. PMID:28117136

Breaking barriers to novel analgesic drug development.

PubMed

Yekkirala, Ajay S; Roberson, David P; Bean, Bruce P; Woolf, Clifford J

2017-08-01

Acute and chronic pain complaints, although common, are generally poorly served by existing therapies. This unmet clinical need reflects a failure to develop novel classes of analgesics with superior efficacy, diminished adverse effects and a lower abuse liability than those currently available. Reasons for this include the heterogeneity of clinical pain conditions, the complexity and diversity of underlying pathophysiological mechanisms, and the unreliability of some preclinical pain models. However, recent advances in our understanding of the neurobiology of pain are beginning to offer opportunities for developing novel therapeutic strategies and revisiting existing targets, including modulating ion channels, enzymes and G-protein-coupled receptors.

Challenges and opportunities for pediatric severe TBI-review of the evidence and exploring a way forward.

PubMed

Bell, Michael J; Adelson, P David; Wisniewski, Stephen R

2017-10-01

Traumatic brain injury (TBI) is a leading killer of children in the developed and developing world. Despite evidence-based guidelines and several recent clinical trials, the progress in developing best practices for children with severe TBI has been slow. This article describes (i) the burden of the disease, (ii) the inadequacies of the evidence-based guidelines, (iii) the failure of the largest clinical trials to prove their primary hypotheses, and (iv) possible advances from an observational cohort study called the Approaches and Decisions for Acute Pediatric TBI (ADAPT) Trial that has recently completed enrollment.

Breaking barriers to novel analgesic drug development

PubMed Central

Yekkirala, Ajay S; Roberson, David P; Bean, Bruce P.; Woolf, Clifford J.

2017-01-01

Acute and chronic pain complaints, while very common, are generally poorly served by existing therapies. The unmet clinical need reflects the failure in developing novel classes of analgesics with superior efficacy, diminished adverse effects and a lower abuse liability than those currently available. Reasons for this include the heterogeneity of clinical pain conditions, the complexity and diversity of underlying pathophysiological mechanisms coupled with the unreliability of some preclinical pain models. However, recent advances in our understanding of the neurobiology of pain are beginning to offer opportunities to develop new therapeutic strategies and revisit existing targets, including modulating ion channels, enzymes and GPCRs. PMID:28596533

GSK's antigen-specific cancer immunotherapy programme: pilot results leading to Phase III clinical development.

PubMed

Brichard, Vincent G; Lejeune, Diane

2007-09-27

From the first evidence that the immune system could recognize tumors, different types of tumor antigens have been identified and deeply characterized. Several different approaches aimed at targeting these antigens have already been the subject of clinical studies. In this field, the GSK Biologicals' approach relying on recombinant proteins combined with an immunological Adjuvant System in a specific clinical setting, has entertained hopes of developing a new class of well tolerated anti-cancer therapy. This methodology led to promising advances with MAGE-A3 immunotherapy in NSCLC and has the potential to be applied to all tumor types.

Bruton’s tyrosine kinase inhibitors and their clinical potential in the treatment of B-cell malignancies: focus on ibrutinib

PubMed Central

Aalipour, Amin

2014-01-01

Aberrant signaling of the B-cell receptor pathway has been linked to the development and maintenance of B-cell malignancies. Bruton’s tyrosine kinase (BTK), a protein early in this pathway, has emerged as a new therapeutic target in a variety of such malignancies. Ibrutinib, the most clinically advanced small molecule inhibitor of BTK, has demonstrated impressive tolerability and activity in a range of B-cell lymphomas which led to its recent approval for relapsed mantle cell lymphoma and chronic lymphocytic leukemia. This review focuses on the preclinical and clinical development of ibrutinib and discusses its therapeutic potential. PMID:25360238

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.

The development, past achievements, and future directions of brain PET

PubMed Central

Jones, Terry; Rabiner, Eugenii A

2012-01-01

The early developments of brain positron emission tomography (PET), including the methodological advances that have driven progress, are outlined. The considerable past achievements of brain PET have been summarized in collaboration with contributing experts in specific clinical applications including cerebrovascular disease, movement disorders, dementia, epilepsy, schizophrenia, addiction, depression and anxiety, brain tumors, drug development, and the normal healthy brain. Despite a history of improving methodology and considerable achievements, brain PET research activity is not growing and appears to have diminished. Assessments of the reasons for decline are presented and strategies proposed for reinvigorating brain PET research. Central to this is widening the access to advanced PET procedures through the introduction of lower cost cyclotron and radiochemistry technologies. The support and expertize of the existing major PET centers, and the recruitment of new biologists, bio-mathematicians and chemists to the field would be important for such a revival. New future applications need to be identified, the scope of targets imaged broadened, and the developed expertize exploited in other areas of medical research. Such reinvigoration of the field would enable PET to continue making significant contributions to advance the understanding of the normal and diseased brain and support the development of advanced treatments. PMID:22434067

Management of advanced prostate cancer in senior adults: the new landscape.

PubMed

Aapro, Matti S

2012-01-01

The landscape of treatment for advanced prostate cancer is continually evolving as new therapies are developed and guidelines are constantly updated. However, the management of older men with advanced disease is not optimal. Many men are denied chemotherapy based on their chronological age, not their health status. Androgen-deprivation therapy (ADT) remains the mainstay of first-line treatment of advanced disease. Once the disease becomes resistant to castration, docetaxel-based chemotherapy is the regulatory-approved standard of care, irrespective of age. The place of weekly docetaxel in patients with poor performance status and signs of frailty has to be further evaluated in clinical studies. New treatments are now available, or on the horizon, for disease that progresses during or after docetaxel therapy. Cabazitaxel and abiraterone have been shown to prolong survival, irrespective of age, and are already in clinical use having received regulatory approval. The optimal sequence for these two agents is still unknown, although there is some indication that in patients predicted to be poor responders to abiraterone (high Gleason score, progression during docetaxel therapy, rapid progression to castrate-resistant prostate cancer with ADT) cabazitaxel should be the preferred choice. Further advances are being investigated, with promising data reported from phase III trials.

Viewing clinical research career development through the lens of social cognitive career theory.

PubMed

Bakken, Lori L; Byars-Winston, Angela; Wang, Min-Fen

2006-02-01

Issues such as, over commitment, insufficient time, and lack of funding, threaten physicians' entry and sustainability in a research career pathway. Social cognitive career theory is presented as a conceptual framework to critically examine the limitations of the National Institutes of Health's (NIH) efforts to promote the career development of physician-scientists. Special attention is given to the unique challenges of promoting this career pathway for women and underrepresented minorities. The authors propose enhanced recommendations for the career development of physician-scientists and research questions for future studies and program development aimed at advancing the nation's efforts to promote clinical research.

Mapping fetal brain development in utero using magnetic resonance imaging: the Big Bang of brain mapping.

PubMed

Studholme, Colin

2011-08-15

The development of tools to construct and investigate probabilistic maps of the adult human brain from magnetic resonance imaging (MRI) has led to advances in both basic neuroscience and clinical diagnosis. These tools are increasingly being applied to brain development in adolescence and childhood, and even to neonatal and premature neonatal imaging. Even earlier in development, parallel advances in clinical fetal MRI have led to its growing use as a tool in challenging medical conditions. This has motivated new engineering developments encompassing optimal fast MRI scans and techniques derived from computer vision, the combination of which allows full 3D imaging of the moving fetal brain in utero without sedation. These promise to provide a new and unprecedented window into early human brain growth. This article reviews the developments that have led us to this point, examines the current state of the art in the fields of fast fetal imaging and motion correction, and describes the tools to analyze dynamically changing fetal brain structure. New methods to deal with developmental tissue segmentation and the construction of spatiotemporal atlases are examined, together with techniques to map fetal brain growth patterns.

Development of glucose-responsive 'smart' insulin systems.

PubMed

Rege, Nischay K; Phillips, Nelson F B; Weiss, Michael A

2017-08-01

The complexity of modern insulin-based therapy for type I and type II diabetes mellitus and the risks associated with excursions in blood-glucose concentration (hyperglycemia and hypoglycemia) have motivated the development of 'smart insulin' technologies (glucose-responsive insulin, GRI). Such analogs or delivery systems are entities that provide insulin activity proportional to the glycemic state of the patient without external monitoring by the patient or healthcare provider. The present review describes the relevant historical background to modern GRI technologies and highlights three distinct approaches: coupling of continuous glucose monitoring (CGM) to deliver devices (algorithm-based 'closed-loop' systems), glucose-responsive polymer encapsulation of insulin, and molecular modification of insulin itself. Recent advances in GRI research utilizing each of the three approaches are illustrated; these include newly developed algorithms for CGM-based insulin delivery systems, glucose-sensitive modifications of existing clinical analogs, newly developed hypoxia-sensitive polymer matrices, and polymer-encapsulated, stem-cell-derived pancreatic β cells. Although GRI technologies have yet to be perfected, the recent advances across several scientific disciplines that are described in this review have provided a path towards their clinical implementation.

Issues related to development of antiepileptogenic therapies.

PubMed

Pitkänen, Asla; Nehlig, Astrid; Brooks-Kayal, Amy R; Dudek, F Edward; Friedman, Daniel; Galanopoulou, Aristea S; Jensen, Frances E; Kaminski, Rafal M; Kapur, Jaideep; Klitgaard, Henrik; Löscher, Wolfgang; Mody, Istvan; Schmidt, Dieter

2013-08-01

Several preclinical proof-of-concept studies have provided evidence for positive treatment effects on epileptogenesis. However, none of these hypothetical treatments has advanced to the clinic. The experience in other fields of neurology such as stroke, Alzheimer's disease, or amyotrophic lateral sclerosis has indicated several problems in the design of preclinical studies, which likely contribute to failures in translating the positive preclinical data to the clinic. The Working Group on "Issues related to development of antiepileptogenic therapies" of the International League Against Epilepsy (ILAE) and the American Epilepsy Society (AES) has considered the possible problems that arise when moving from proof-of-concept antiepileptogenesis (AEG) studies to preclinical AEG trials, and eventually to clinical AEG trials. This article summarizes the discussions and provides recommendations on how to design a preclinical AEG monotherapy trial in adult animals. We specifically address study design, animal and model selection, number of studies needed, issues related to administration of the treatment, outcome measures, statistics, and reporting. In addition, we give recommendations for future actions to advance the preclinical AEG testing. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Biomaterials and Nanotherapeutics for Enhancing Skin Wound Healing

PubMed Central

Das, Subhamoy; Baker, Aaron B.

2016-01-01

Wound healing is an intricate process that requires complex coordination between many cell types and an appropriate extracellular microenvironment. Chronic wounds often suffer from high protease activity, persistent infection, excess inflammation, and hypoxia. While there has been intense investigation to find new methods to improve cutaneous wound care, the management of chronic wounds, burns, and skin wound infection remain challenging clinical problems. Ideally, advanced wound dressings can provide enhanced healing and bridge the gaps in the healing processes that prevent chronic wounds from healing. These technologies have great potential for improving outcomes in patients with poorly healing wounds but face significant barriers in addressing the heterogeneity and clinical complexity of chronic or severe wounds. Active wound dressings aim to enhance the natural healing process and work to counter many aspects that plague poorly healing wounds, including excessive inflammation, ischemia, scarring, and wound infection. This review paper discusses recent advances in the development of biomaterials and nanoparticle therapeutics to enhance wound healing. In particular, this review focuses on the novel cutaneous wound treatments that have undergone significant preclinical development or are currently used in clinical practice. PMID:27843895

Recent advance on genome editing for therapy of β-hemoglobinopathies.

PubMed

Liu, Jia-Wei; Hong, Tao; Qin, Xin; Liang, Ying-Min; Zhang, Ping

2018-02-20

β-hemoglobinopathies are one of six groups of common illnesses affecting human health. Although the genetic mechanisms have been elucidated for several decades, curable treatment options, other than allogeneic bone marrow transplantation, are still lacking. In recent years, rapid development in genome editing technologies and their clinical applications have opened up new directions for treatment of β-hemoglobinopathies. Genome editing technologies, as applied in autologous CD34 + hematopoietic stem and progenitor cells, represents a promising remedial means for the β-globin disorders. Hemoglobin gene mutations could be corrected with homologous recombination-mediated DNA repair pathway to repair the genetic defects, while the nonhomologous end-joining pathway may be used to silence the key repressor of fetal globin expression and reactivate fetal hemoglobin expression, thereby alleviating the clinical symptoms of β-hemoglobinopathies in patients. This review summarizes the recent advances on genome editing of β-hemoglobinopathies from the bench design to the establishment of clinical translational platforms, thereby providing critical insights and references on the application of genome editing technologies for the development of therapeutic strategies for β-hemoglobinopathies.

Image-Based Predictive Modeling of Heart Mechanics.

PubMed

Wang, V Y; Nielsen, P M F; Nash, M P

2015-01-01

Personalized biophysical modeling of the heart is a useful approach for noninvasively analyzing and predicting in vivo cardiac mechanics. Three main developments support this style of analysis: state-of-the-art cardiac imaging technologies, modern computational infrastructure, and advanced mathematical modeling techniques. In vivo measurements of cardiac structure and function can be integrated using sophisticated computational methods to investigate mechanisms of myocardial function and dysfunction, and can aid in clinical diagnosis and developing personalized treatment. In this article, we review the state-of-the-art in cardiac imaging modalities, model-based interpretation of 3D images of cardiac structure and function, and recent advances in modeling that allow personalized predictions of heart mechanics. We discuss how using such image-based modeling frameworks can increase the understanding of the fundamental biophysics behind cardiac mechanics, and assist with diagnosis, surgical guidance, and treatment planning. Addressing the challenges in this field will require a coordinated effort from both the clinical-imaging and modeling communities. We also discuss future directions that can be taken to bridge the gap between basic science and clinical translation.

Therapeutic Gene Editing Safety and Specificity.

PubMed

Lux, Christopher T; Scharenberg, Andrew M

2017-10-01

Therapeutic gene editing is significant for medical advancement. Safety is intricately linked to the specificity of the editing tools used to cut at precise genomic targets. Improvements can be achieved by thoughtful design of nucleases and repair templates, analysis of off-target editing, and careful utilization of viral vectors. Advancements in DNA repair mechanisms and development of new generations of tools improve targeting of specific sequences while minimizing risks. It is important to plot a safe course for future clinical trials. This article reviews safety and specificity for therapeutic gene editing to spur dialogue and advancement. Copyright © 2017 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.

Nutrition impact symptoms in advanced cancer patients: frequency and specific interventions, a case-control study.

PubMed

Omlin, Aurelius; Blum, David; Wierecky, Jan; Haile, Sarah R; Ottery, Faith D; Strasser, Florian

2013-03-01

Involuntary weight loss (IWL) is frequent in advanced cancer patients causing compromised anticancer treatment outcomes and function. Cancer cachexia is influenced by nutrition impact symptoms (NIS). The aim of this study was to explore the frequency of NIS in advanced patients and to assess specific interventions guided by a 12-item NIS checklist. Consecutive patients from an outpatient nutrition-fatigue clinic completed the NIS checklist. The NIS checklist was developed based on literature review and multiprofessional clinical expert consensus. Chart review was performed to detect defined NIS typical interventions. Oncology outpatients not seen in the nutrition-fatigue clinic were matched for age, sex, and tumor to serve as controls. In 52 nutrition-fatigue clinic patients, a mixed cancer population [IWL in 2 months 5.96 % (mean)], the five most frequent NIS were taste and smell alterations 27 %, constipation 19 %, abdominal pain 14 %, dysphagia 12 %, and epigastric pain 10 %. A statistically significant difference for NIS typical interventions in patients with taste and smell alterations (p = 0.04), constipation (p = 0.01), pain (p = 0.0001), and fatigue (p = 0.0004) were found compared to the control population [mixed cancer, 3.53 % IWL in 2 months (mean)]. NIS are common in advanced cancer patients. The NIS checklist can guide therapeutic nutrition-targeted interventions. The awareness for NIS will likely evoke more research in assessment, impact, and treatment.

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.

Advancing staff development and progression in nursing.

PubMed

Narayanasamy, Aru; Narayanasamy, Mani

Staff development in the NHS is integral to clinical governance and therefore important to health service providers. It is concerned with all the activities that advance knowledge, skills and attitudes of staff, embracing induction, mentorship, continuing professional development, learning beyond registration, performance appraisals, promotion, personal and professional development, and related activities. The recent contraction in nursing posts and services and competition for jobs means that only well-qualified staff with an impressive portfolio of staff development are likely to climb the career ladder. Nursing staff development and training needs in the NHS are huge and multifaceted. Healthcare providers need to invest in clear staff development strategies if they are to maintain their status as effective care delivery organizations in an increasingly competitive market-driven economy. This article examines the many features of staff development and highlights the benefits for both staff and organizations.

How to emerge from the conservatism in clinical research methodology?

PubMed

Kotecki, Nuria; Penel, Nicolas; Awada, Ahmad

2017-09-01

Despite recent changes in clinical research methodology, many challenges remain in drug development methodology. Advances in molecular biology and cancer treatments have changed the clinical research landscape. Thus, we moved from empirical clinical oncology to molecular and immunological therapeutic approaches. Along with this move, adapted dose-limiting toxicities definitions, endpoints, and dose escalation methods have been proposed. Moreover, the classical frontier between phase I, phase II, and phase III has become unclear in particular for immunological approaches. So, investigators are facing major challenges in drug development methodology. We propose to individualize clinical research using innovative approaches to significantly improve patient outcomes and targeting what is considered unmet need. Integrating high level of translational research and performing well designed biomarker studies with great potential for clinical practice are of utmost importance. This could be performed within new models of clinical research networks and by building a strong collaboration between academic, cooperative groups, on-site investigators, and pharma.

Quality assurance of radiotherapy in cancer treatment: toward improvement of patient safety and quality of care.

PubMed

Ishikura, Satoshi

2008-11-01

The process of radiotherapy (RT) is complex and involves understanding of the principles of medical physics, radiobiology, radiation safety, dosimetry, radiation treatment planning, simulation and interaction of radiation with other treatment modalities. Each step in the integrated process of RT needs quality control and quality assurance (QA) to prevent errors and to give high confidence that patients will receive the prescribed treatment correctly. Recent advances in RT, including intensity-modulated and image-guided RT, focus on the need for a systematic RTQA program that balances patient safety and quality with available resources. It is necessary to develop more formal error mitigation and process analysis methods, such as failure mode and effect analysis, to focus available QA resources optimally on process components. External audit programs are also effective. The International Atomic Energy Agency has operated both an on-site and off-site postal dosimetry audit to improve practice and to assure the dose from RT equipment. Several countries have adopted a similar approach for national clinical auditing. In addition, clinical trial QA has a significant role in enhancing the quality of care. The Advanced Technology Consortium has pioneered the development of an infrastructure and QA method for advanced technology clinical trials, including credentialing and individual case review. These activities have an impact not only on the treatment received by patients enrolled in clinical trials, but also on the quality of treatment administered to all patients treated in each institution, and have been adopted globally; by the USA, Europe and Japan also.

An Overview of the History of Orthopedic Surgery.

PubMed

Swarup, Ishaan; O'Donnell, Joseph F

Orthopedic surgery has a long and rich history. While the modern term orthopedics was coined in the 1700s, orthopedic principles were beginning to be developed and used during primitive times. The Egyptians continued these practices, and described ways to recognize and manage common orthopedic conditions. The Greeks and Romans subsequently began to study medicine in a systematic manner, and greatly improved our understanding of orthopedic anatomy and surgical technique. After a period of little progress during the Middle Ages, rapid advancement was noted during the Renaissance, including the description of various injuries, improvements in surgical technique, and development of orthopedic hospitals. Collectively, these advances provided the foundation for modern orthopedics. Currently, orthopedic surgery is a rapidly developing field that has benefited from the works of numerous scholars and surgeons. It is important to recognize the successes and failures of the past, in order to advance research and practice as well as improve patient care and clinical outcomes.

Vaccine development for emerging virulent infectious diseases.

PubMed

Maslow, Joel N

2017-10-04

The recent outbreak of Zaire Ebola virus in West Africa altered the classical paradigm of vaccine development and that for emerging infectious diseases (EIDs) in general. In this paper, the precepts of vaccine discovery and advancement through pre-clinical and clinical assessment are discussed in the context of the recent Ebola virus, Middle East Respiratory Syndrome coronavirus (MERS-CoV), and Zika virus outbreaks. Clinical trial design for diseases with high mortality rates and/or high morbidity in the face of a global perception of immediate need and the factors that drive design in the face of a changing epidemiology are presented. Vaccines for EIDs thus present a unique paradigm to standard development precepts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development and promotion in translational medicine: perspectives from 2012 sino-american symposium on clinical and translational medicine

PubMed Central

2012-01-01

Background Clinical translational medicine (CTM) is an emerging area comprising multidisciplinary research from basic science to medical applications and entails a close collaboration among hospital, academia and industry. Findings This Session focused discussing on new models for project development and promotion in translational medicine. The conference stimulated the scientific and commercial communication of project development between academies and companies, shared the advanced knowledge and expertise of clinical applications, and created the environment for collaborations. Conclusions Although strategic collaborations between corporate and academic institutions have resulted in a state of resurgence in the market, new cooperation models still need time to tell whether they will improve the translational medicine process. PMID:23369198

Osteoporosis treatment: recent developments and ongoing challenges

PubMed Central

Khosla, Sundeep; Hofbauer, Lorenz C

2018-01-01

Osteoporosis is an enormous and growing public health problem. Once considered an inevitable consequence of ageing, it is now eminently preventable and treatable. Ironically, despite tremendous therapeutic advances, there is an increasing treatment gap for patients at high fracture risk. In this Series paper, we trace the evolution of drug therapy for osteoporosis, which began in the 1940s with the demonstration by Fuller Albright that treatment with oestrogen could reverse the negative calcium balance that developed in women after menopause or oophorectomy. We note a watershed in osteoporosis drug discovery around the year 2000, when the approach to developing novel therapeutics shifted from one driven by discoveries in animal studies and clinical observations (eg, oestrogen, calcitonin, and teriparatide) or opportunistic repurposing of existing compounds (eg, bisphosphonates) to one driven by advances in fundamental bone biology (eg, denosumab) coupled with clues from patients with rare bone diseases (eg, romosozumab, odanacatib). Despite these remarkable advances, concerns about rare side-effects of anti-resorptive drugs, particularly bisphosphonates, and the absence of clear evidence in support of their long-term efficacy is leading many patients who could benefit from drug therapy to not take these drugs. As such, there remains an important clinical need to develop ways to enhance patient acceptance and compliance with these effective drugs, and to continue to develop new drugs that do not cause these side-effects and have prolonged anabolic effects on bone. Such changes could lead to a true reversal of this potentially devastating disease of ageing. PMID:28689769

Status of vaccine research and development of vaccines for malaria.

PubMed

Birkett, Ashley J

2016-06-03

Despite recent progress in reducing deaths attributable to malaria, it continues to claim approximately 500,000 lives per year and is associated with approximately 200 million infections. New tools, including safe and effective vaccines, are needed to ensure that the gains of the last 15 years are leveraged toward achieving the ultimate goal of malaria parasite eradication. In 2015, the European Medicines Agency announced the adoption of a positive opinion for the malaria vaccine candidate most advanced in development, RTS,S/AS01, which provides modest protection against clinical malaria; in early 2016, WHO recommended large-scale pilot implementations of RTS,S in settings of moderate-to-high malaria transmission. In alignment with these advancements, the community goals and preferred product characteristics for next-generation vaccines have been updated to inform the development of vaccines that are highly efficacious in preventing clinical malaria, and those needed to accelerate parasite elimination. Next-generation vaccines, targeting all stages of the parasite lifecycle, are in early-stage development with the most advanced in Phase 2 trials. Importantly, progress is being made in the definition of feasible regulatory pathways to accelerate timelines, including for vaccines designed to interrupt transmission of parasites from humans to mosquitoes. The continued absence of financially lucrative, high-income markets to drive investment in malaria vaccine development points to continued heavy reliance on public and philanthropic funding. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Human Cancer Models Initiative | Office of Cancer Genomics

Cancer.gov

The Human Cancer Models Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models, which are annotated with genomic and clinical data. In an effort to advance cancer research and more fully understand how in vitro findings are related to clinical biology, HCMI-developed models and related data will be available as a community resource for cancer and other research.

Human Cancer Models Initiative | Office of Cancer Genomics

Cancer.gov

The Human Cancer Models Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models, which are annotated with genomic and clinical data. In an effort to advance cancer research and more fully understand how in vitro findings are related to clinical biology, HCMI-developed models and related data will be available as a community resource for cancer research.

Blood substitutes.

PubMed Central

Kostrzewska, E.

1976-01-01

With the development of modern methods of surgery, anaesthesia, and pre- and postoperative care the requirement for blood substitutes is continuously increasing. We present a review of the different blood substitutes which are already in clinical use or in an advanced stage of experimental investigation for possible practical administration. Our own clinical experience with dextrans and experimental studies on stroma-free haemoglobin and hydroxyethyl starch solutions are described. PMID:57736

Molecular imaging in drug development: Update and challenges for radiolabeled antibodies and nanotechnology.

PubMed

Colombo, Ilaria; Overchuk, Marta; Chen, Juan; Reilly, Raymond M; Zheng, Gang; Lheureux, Stephanie

2017-11-01

Despite the significant advancement achieved in understanding the molecular mechanisms responsible for cancer transformation and aberrant proliferation, leading to novel targeted cancer therapies, significant effort is still needed to "personalize" cancer treatment. Molecular imaging is an emerging field that has shown the ability to characterize in vivo the molecular pathways present at the cancer cell level, enabling diagnosis and personalized treatment of malignancies. These technologies, particularly SPECT and PET also permit the development of novel radiotheranostic probes, which provide capabilities for diagnosis and treatment with the same agent. The small therapeutic index of most anticancer agents is a limitation in the drug development process. Incorporation of molecular imaging in clinical research may help in overcoming this limitation and favouring selection of patient populations most likely to achieve benefit from targeted therapy. This review will focus on two of the most advanced theranostic approaches with promising potential for application in the clinic: 1) therapeutic monoclonal antibodies which may be linked to a radionuclide for SPECT or PET imaging to guide cancer diagnosis, staging, molecular characterization, and assessment of the response to treatment and 2) multifunctional nanotechnology that allows image guided drug delivery through encapsulation of multiple therapeutic, targeting and imaging agents into a single nanoparticle. Porphysome, a liposome-like nanoparticle, is an example of a novel and promising application of nanotechnology for cancer diagnosis and treatment. These technologies have proven to be effective in preclinical models, warranting further clinical investigation to advance their application for the benefit of cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Three upper limb robotic devices for stroke rehabilitation: a review and clinical perspective.

PubMed

Bishop, Lauri; Stein, Joel

2013-01-01

Stroke is a leading cause of disability worldwide. Many survivors of stroke remain with residual disabilities, even years later. Advances in technology have led to the development of a variety of robotic devices for use in rehabilitation. The integration of robotics in the delivery of neurorehabilitation is promising, but still not widely used in clinical settings. The aim of this review is to discuss the general design of three typical upper limb robotic devices, and examine the practical considerations for their use in a clinical environment. Each device is described, the available clinical literature is reviewed and a clinical perspective is given on the usefulness of these robotic devices in rehabilitation of this population. Current literature supports the use of robotics in the clinical environment. However, claims that robotic therapy is more effective than traditional treatment is not substantially supported. The majority of clinical trials reported are small, and lack the use of a control group for comparison treatment. The use of robotics in stroke rehabilitation is still a relatively new treatment platform, and still evolving. As technological advances are made, there is much potential for growth in this field.

Learning through vulnerability: a mentor-mentee experience.

PubMed

Jones, Kohar; Reis, Shmuel

2010-01-01

The following essay, drawn from the journals and work notebook of a family medicine resident and a visiting clinical mentor, chronicles their work together in an Advanced Clinical Mentoring program. This program included afternoons of direct clinical observation immediately followed by feedback sessions. In addition to addressing specific professional issues, such as time management, limiting patient encounters, agenda matching, and the One-Minute Preceptor model, the authors developed personally as they opened themselves to learning and growing as a clinician and a teacher.

Novel end points for clinical trials in young children with cystic fibrosis.

PubMed

Simpson, Shannon J; Mott, Lauren S; Esther, Charles R; Stick, Stephen M; Hall, Graham L

2013-06-01

Cystic fibrosis (CF) lung disease commences early in the disease progression and is the most common cause of mortality. While new CF disease-modifying agents are currently undergoing clinical trial evaluation, the implementation of such trials in young children is limited by the lack of age-appropriate clinical trial end points. Advances in infant and preschool lung function testing, imaging of the chest and the development of biochemical biomarkers have led to increased possibility of quantifying mild lung disease in young children with CF and objectively monitoring disease progression over the course of an intervention. Despite this, further standardization and development of these techniques is required to provide robust objective measures for clinical trials in this age group.

A look backward and forward in the regulatory and treatment history of multiple myeloma: Approval of novel-novel agents, new drug development, and longer patient survival.

PubMed

Kazandjian, Dickran; Landgren, Ola

2016-12-01

The past decade has seen significant advances in our understanding and treatment of multiple myeloma (MM) and its precursor diseases. These advances include gains in knowledge of the underlying pathobiology including molecular and cellular prognostic factors for disease progression. In parallel we have witnessed the availability of novel therapeutics. Together these advances have translated into improvements in long-term clinical benefit and survival in MM. Indeed, it has been shown that patients diagnosed in the last decade have experienced almost doubling of median survival time. We aim to review and give further insight into drug development and novel drug approvals that have revolutionized the treatment of MM. Published by Elsevier Inc.

Community pharmacists and Colleges of Pharmacy: the Ohio partnership.

PubMed

Sweeney, Marc A; Mauro, Vincent F; Cable, Gerald L; Rudnicki, Barbara M; Wall, Andrea L; Murphy, Christine C; Makarich, Joseph A; Kahaleh, Abir A

2005-01-01

To develop pharmacist practice standards, pharmacy preceptor standards, and objectives for students completing advanced practice community pharmacy rotations. Ohio. Pharmacy schools and community pharmacies that serve as advanced practice rotation sites. Developed standards for preceptors and objectives for student experiences. Focus groups that included both community pharmacists and pharmacy faculty collaborated on defining key standards for advanced community pharmacy rotations. Not applicable. Three main documents were produced in this initiative, and these are provided as appendices to this article. Professional and patient care guidelines for preceptors define minimum standards for these role models. Expectations of pharmacists as preceptors provide insights for managing this student-teacher relationship, which is fundamentally different from the more common employer-employee and coworker relationships found in pharmacies of all types. Objectives for student experiences during advanced practice community pharmacy rotations present core expectations in clinical, dispensing, patient education, wellness, and drug information areas. Through this collaboration, Ohio colleges of pharmacy developed a partnership with practitioners in community settings that should enhance the Ohio experiential educational program for student pharmacists. Use of the established guidelines will help educators and practitioners achieve their shared vision for advanced practice community pharmacy rotations and promote high-quality patient care.

Psychiatric epidemiology: selected recent advances and future directions.

PubMed Central

Kessler, R. C.

2000-01-01

Reviewed in this article are selected recent advances and future challenges for psychiatric epidemiology. Major advances in descriptive psychiatric epidemiology in recent years include the development of reliable and valid fully structured diagnostic interviews, the implementation of parallel cross-national surveys of the prevalences and correlates of mental disorders, and the initiation of research in clinical epidemiology. Remaining challenges include the refinement of diagnostic categories and criteria, recognition and evaluation of systematic underreporting bias in surveys of mental disorders, creation and use of accurate assessment tools for studying disorders of children, adolescents, the elderly, and people in less developed countries, and setting up systems to carry out small area estimations for needs assessment and programme planning. Advances in analytical and experimental epidemiology have been more modest. A major challenge is for psychiatric epidemiologists to increase the relevance of their analytical research to their colleagues in preventative psychiatry as well as to social policy analysts. Another challenge is to develop interventions aimed at increasing the proportion of people with mental disorders who receive treatment. Despite encouraging advances, much work still needs to be conducted before psychiatric epidemiology can realize its potential to improve the mental health of populations. PMID:10885165

The role of antiangiogenesis therapy: bevacizumab and beyond.

PubMed

Cortés-Funes, Hernán

2009-06-01

The importance of angiogenesis in tumour growth and development is well known. Overexpression of vascular endothelial growth factor (VEGF), the key mediator of angiogenesis, is associated with poor prognosis in cancer. As a result, several therapeutic agents that inhibit the actions of VEGF or its receptors are currently in development for use in advanced solid tumours, such breast, colorectal, lung and renal cancer. Clinical data from trials of anti-VEGF agents in this group of tumours are discussed, with a particular focus on the efficacy and safety of bevacizumab, the anti-VEGF agent at the most advanced stage of development in those tumour types. Future potential uses of bevacizumab in cancer therapy will be discussed.

Advances in natural biomaterials for nerve tissue repair.

PubMed

Khaing, Zin Z; Schmidt, Christine E

2012-06-25

Natural biomaterials are well positioned to play a significant role in the development of the next generation of biomaterials for nervous system repair. These materials are derived from naturally occurring substances and are highly diverse and versatile. They are generally biocompatible and are well tolerated in vivo, and therefore have a high potential to be successful as part of clinical repair strategies in the nervous system. Here we review recent reports on acellular tissue grafts, collagen, hyaluronan, fibrin, and agarose in their use to repair the nervous system. In addition, newly developed advanced fabrication techniques to further develop the next generation natural biomaterials-based therapeutic devices are discussed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Advances in non-dopaminergic treatments for Parkinson's disease

PubMed Central

Stayte, Sandy; Vissel, Bryce

2014-01-01

Since the 1960's treatments for Parkinson's disease (PD) have traditionally been directed to restore or replace dopamine, with L-Dopa being the gold standard. However, chronic L-Dopa use is associated with debilitating dyskinesias, limiting its effectiveness. This has resulted in extensive efforts to develop new therapies that work in ways other than restoring or replacing dopamine. Here we describe newly emerging non-dopaminergic therapeutic strategies for PD, including drugs targeting adenosine, glutamate, adrenergic, and serotonin receptors, as well as GLP-1 agonists, calcium channel blockers, iron chelators, anti-inflammatories, neurotrophic factors, and gene therapies. We provide a detailed account of their success in animal models and their translation to human clinical trials. We then consider how advances in understanding the mechanisms of PD, genetics, the possibility that PD may consist of multiple disease states, understanding of the etiology of PD in non-dopaminergic regions as well as advances in clinical trial design will be essential for ongoing advances. We conclude that despite the challenges ahead, patients have much cause for optimism that novel therapeutics that offer better disease management and/or which slow disease progression are inevitable. PMID:24904259

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.

Next-generation sequencing in the clinic: promises and challenges.

PubMed

Xuan, Jiekun; Yu, Ying; Qing, Tao; Guo, Lei; Shi, Leming

2013-11-01

The advent of next generation sequencing (NGS) technologies has revolutionized the field of genomics, enabling fast and cost-effective generation of genome-scale sequence data with exquisite resolution and accuracy. Over the past years, rapid technological advances led by academic institutions and companies have continued to broaden NGS applications from research to the clinic. A recent crop of discoveries have highlighted the medical impact of NGS technologies on Mendelian and complex diseases, particularly cancer. However, the ever-increasing pace of NGS adoption presents enormous challenges in terms of data processing, storage, management and interpretation as well as sequencing quality control, which hinder the translation from sequence data into clinical practice. In this review, we first summarize the technical characteristics and performance of current NGS platforms. We further highlight advances in the applications of NGS technologies towards the development of clinical diagnostics and therapeutics. Common issues in NGS workflows are also discussed to guide the selection of NGS platforms and pipelines for specific research purposes. Published by Elsevier Ireland Ltd.

Test Review: Advanced Clinical Solutions for WAIS-IV and WMS-IV

ERIC Educational Resources Information Center

Chu, Yiting; Lai, Mark H. C.; Xu, Yining; Zhou, Yuanyuan

2012-01-01

The authors review the "Advanced Clinical Solutions for WAIS-IV and WMS-IV". The "Advanced Clinical Solutions (ACS) for the Wechsler Adult Intelligence Scale-Fourth Edition" (WAIS-IV; Wechsler, 2008) and the "Wechsler Memory Scale-Fourth Edition" (WMS-IV; Wechsler, 2009) was published by Pearson in 2009. It is a…

Prospects and applications of nanobiotechnology: a medical perspective.

PubMed

Fakruddin, Md; Hossain, Zakir; Afroz, Hafsa

2012-07-20

Nanobiotechnology is the application of nanotechnology in biological fields. Nanotechnology is a multidisciplinary field that currently recruits approach, technology and facility available in conventional as well as advanced avenues of engineering, physics, chemistry and biology. A comprehensive review of the literature on the principles, limitations, challenges, improvements and applications of nanotechnology in medical science was performed. Nanobiotechnology has multitude of potentials for advancing medical science thereby improving health care practices around the world. Many novel nanoparticles and nanodevices are expected to be used, with an enormous positive impact on human health. While true clinical applications of nanotechnology are still practically inexistent, a significant number of promising medical projects are in an advanced experimental stage. Implementation of nanotechnology in medicine and physiology means that mechanisms and devices are so technically designed that they can interact with sub-cellular (i.e. molecular) levels of the body with a high degree of specificity. Thus therapeutic efficacy can be achieved to maximum with minimal side effects by means of the targeted cell or tissue-specific clinical intervention. More detailed research and careful clinical trials are still required to introduce diverse components of nanobiotechnology in random clinical applications with success. Ethical and moral concerns also need to be addressed in parallel with the new developments.

Prospects and applications of nanobiotechnology: a medical perspective

PubMed Central

2012-01-01

Background Nanobiotechnology is the application of nanotechnology in biological fields. Nanotechnology is a multidisciplinary field that currently recruits approach, technology and facility available in conventional as well as advanced avenues of engineering, physics, chemistry and biology. Method A comprehensive review of the literature on the principles, limitations, challenges, improvements and applications of nanotechnology in medical science was performed. Results Nanobiotechnology has multitude of potentials for advancing medical science thereby improving health care practices around the world. Many novel nanoparticles and nanodevices are expected to be used, with an enormous positive impact on human health. While true clinical applications of nanotechnology are still practically inexistent, a significant number of promising medical projects are in an advanced experimental stage. Implementation of nanotechnology in medicine and physiology means that mechanisms and devices are so technically designed that they can interact with sub-cellular (i.e. molecular) levels of the body with a high degree of specificity. Thus therapeutic efficacy can be achieved to maximum with minimal side effects by means of the targeted cell or tissue-specific clinical intervention. Conclusion More detailed research and careful clinical trials are still required to introduce diverse components of nanobiotechnology in random clinical applications with success. Ethical and moral concerns also need to be addressed in parallel with the new developments. PMID:22817658

Treating autoimmune disorders with venom-derived peptides.

PubMed

Shen, Bingzheng; Cao, Zhijian; Li, Wenxin; Sabatier, Jean-Marc; Wu, Yingliang

2017-09-01

The effective treatment of autoimmune diseases remains a challenge. Voltage-gated potassium Kv1.3 channels, which are expressed in lymphocytes, are a new therapeutic target for treating autoimmune disease. Consequently, Kv1.3 channel-inhibiting venom-derived peptides are a prospective resource for new drug discovery and clinical application. Area covered: Preclinical and clinical studies have produced a wealth of information on Kv1.3 channel-inhibiting venom-derived peptides, especially from venomous scorpions and sea anemones. This review highlights the advances in screening and design of these peptides with diverse structures and potencies. It focuses on representative strategies for improving peptide selectivity and discusses the preclinical research on those venom-derived peptides as well as their clinical developmental status. Expert opinion: Encouraging results indicate that peptides isolated from the venom of venomous animals are a large resource for discovering immunomodulators that act on Kv1.3 channels. Since the structural diversity of venom-derived peptides determines the variety of their pharmacological activities, the design and optimization of venom-peptides for improved Kv1.3 channel-specificity has been advanced through some representative strategies, such as peptide chemical modification, amino acid residue truncation and binding interface modulation. These advances should further accelerate research, development and the future clinical application of venom-derived peptides selectively targeting Kv1.3 channels.

[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.

Establishing advanced practice for medical imaging in New Zealand

PubMed Central

Yielder, Jill; Young, Adrienne; Park, Shelley; Coleman, Karen

2014-01-01

IntroductionThis article presents the outcome and recommendations following the second stage of a role development project conducted on behalf of the New Zealand Institute of Medical Radiation Technology (NZIMRT). The study sought to support the development of profiles and criteria that may be used to formulate Advanced Scopes of Practice for the profession. It commenced in 2011, following on from initial research that occurred between 2005 and 2008 investigating role development and a possible career structure for medical radiation technologists (MRTs) in New Zealand (NZ). MethodsThe study sought to support the development of profiles and criteria that could be used to develop Advanced Scopes of Practice for the profession through inviting 12 specialist medical imaging groups in NZ to participate in a survey. ResultsFindings showed strong agreement on potential profiles and on generic criteria within them; however, there was less agreement on specific skills criteria within specialist areas. ConclusionsThe authors recommend that one Advanced Scope of Practice be developed for Medical Imaging, with the establishment of generic and specialist criteria. Systems for approval of the overall criteria package for any individual Advanced Practitioner (AP) profile, audit and continuing professional development requirements need to be established by the Medical Radiation Technologists Board (MRTB) to meet the local needs of clinical departments. It is further recommended that the NZIMRT and MRTB promote and support the need for an AP pathway for medical imaging in NZ. PMID:26229631

Establishing advanced practice for medical imaging in New Zealand

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

Yielder, Jill, E-mail: j.yielder@auckland.ac.nz; Young, Adrienne; Park, Shelley

Introduction: This article presents the outcome and recommendations following the second stage of a role development project conducted on behalf of the New Zealand Institute of Medical Radiation Technology (NZIMRT). The study sought to support the development of profiles and criteria that may be used to formulate Advanced Scopes of Practice for the profession. It commenced in 2011, following on from initial research that occurred between 2005 and 2008 investigating role development and a possible career structure for medical radiation technologists (MRTs) in New Zealand (NZ). Methods: The study sought to support the development of profiles and criteria that couldmore » be used to develop Advanced Scopes of Practice for the profession through inviting 12 specialist medical imaging groups in NZ to participate in a survey. Results: Findings showed strong agreement on potential profiles and on generic criteria within them; however, there was less agreement on specific skills criteria within specialist areas. Conclusions: The authors recommend that one Advanced Scope of Practice be developed for Medical Imaging, with the establishment of generic and specialist criteria. Systems for approval of the overall criteria package for any individual Advanced Practitioner (AP) profile, audit and continuing professional development requirements need to be established by the Medical Radiation Technologists Board (MRTB) to meet the local needs of clinical departments. It is further recommended that the NZIMRT and MRTB promote and support the need for an AP pathway for medical imaging in NZ.« less

New antituberculous drugs derived from natural products: current perspectives and issues in antituberculous drug development.

PubMed

Igarashi, Masayuki; Ishizaki, Yoshimasa; Takahashi, Yoshiaki

2017-11-01

Tuberculosis is one of the most common and challenging infectious diseases worldwide. Especially, the lack of effective chemotherapeutic drugs for tuberculosis/human immunodeficiency virus co-infection and prevalence of multidrug-resistant and extensively drug-resistant tuberculosis remain to be serious clinical problems. Development of new drugs is a potential solution to fight tuberculosis. In this decade, the development status of new antituberculous drugs has been greatly advanced by the leading role of international organizations such as the Global Alliance for Tuberculosis Drug Development, Stop Tuberculosis Partnership and Global Health Innovative Technology Fund. In this review, we introduce the development status of new drugs for tuberculosis, focusing on those derived from natural products.The Journal of Antibiotics advance online publication, 1 November 2017; doi:10.1038/ja.2017.126.

mobilityRERC state of the science conference: Considerations for developing an evidence base for wheeled mobility and seating service delivery.

PubMed

Cohen, Laura; Greer, Nancy; Berliner, Elise; Sprigle, Stephen

2013-11-01

This article, developed as background content for discussion during the Mobility Rehabilitation Engineering Research Center State of the Science Conference, reviews research surrounding wheeled mobility and seating (WMS) service delivery, discusses the challenges of improving clinical decision-making, and discusses research approaches used to study and improve health services in other practice areas that might be leveraged to develop the evidence base for WMS. Narrative literature review. An overview of existing research found general agreement across models of WMS service delivery but little high quality evidence to support the recommended approaches and few studies of the relationship between service delivery steps and individual patient outcomes. The definition of successful clinical decision-making is different for different stakeholders. Clinical decision-making should incorporate the best available evidence along with patient values, preferences, circumstances, and clinical expertise. To advance the evidence base for WMS service delivery, alternatives to randomized controlled trials should be considered and reliable and valid outcome measures developed. Technological advances offer tremendous opportunities for individuals with complex rehabilitation technology needs. However, with ongoing scrutiny of WMS service delivery there is an increased need for evidence to support the clinical decision-making process and to support evidence-based coverage policies for WMS services and technologies. An evidence base for wheeled mobility and seating services is an important component of the clinical decision-making process. At present, there is little evidence regarding essential components of the wheeled mobility and seating evaluation or the relationship between the evaluation process and patient outcomes. Many factors can confound this relationship and present challenges to research in this area. All stakeholders (i.e. clinicians, rehabilitation technology suppliers, manufacturers, researchers, payers, policy makers, and wheelchair users) need to work together to develop and support an evidence base for wheeled mobility and seating service delivery.

Transcriptomics in cancer diagnostics: developments in technology, clinical research and commercialization.

PubMed

Sager, Monica; Yeat, Nai Chien; Pajaro-Van der Stadt, Stefan; Lin, Charlotte; Ren, Qiuyin; Lin, Jimmy

2015-01-01

Transcriptomic technologies are evolving to diagnose cancer earlier and more accurately to provide greater predictive and prognostic utility to oncologists and patients. Digital techniques such as RNA sequencing are replacing still-imaging techniques to provide more detailed analysis of the transcriptome and aberrant expression that causes oncogenesis, while companion diagnostics are developing to determine the likely effectiveness of targeted treatments. This article examines recent advancements in molecular profiling research and technology as applied to cancer diagnosis, clinical applications and predictions for the future of personalized medicine in oncology.

Novel Androgen Deprivation Therapy (ADT) in the Treatment of Advanced Prostate Cancer.

PubMed

Aragon-Ching, Jeanny B; Dahut, William L

2010-07-01

Androgen deprivation therapy has been the mainstay of treatment for advanced and metastatic prostate cancer. The use of novel agents targeting the androgen receptor and its signaling pathways offers a promising approach that is both safe and effective. We describe the rationale behind the use of these compounds in clinical development and the existing challenges as to how best to incorporate these new and emerging therapies in the changing treatment paradigm of metastatic prostate cancer.

An evolving scientific basis for the prevention and treatment of pediatric obesity

PubMed Central

Katzmarzyk, PT; Barlow, S; Bouchard, C; Catalano, PM; Hsia, DS; Inge, TH; Lovelady, C; Raynor, H; Redman, LM; Staiano, AE; Spruijt-Metz, D; Symonds, ME; Vickers, M; Wilfley, D; Yanovski, JA

2014-01-01

The 2013 Pennington Biomedical Research Center’s Scientific Symposium focused on the treatment and management of pediatric obesity and was designed to (i) review recent scientific advances in the prevention, clinical treatment and management of pediatric obesity, (ii) integrate the latest published and unpublished findings and (iii) explore how these advances can be integrated into clinical and public health approaches. The symposium provided an overview of important new advances in the field, which led to several recommendations for incorporating the scientific evidence into practice. The science presented covered a range of topics related to pediatric obesity, including the role of genetic differences, epigenetic events influenced by in utero development, pre-pregnancy maternal obesity status, maternal nutrition and maternal weight gain on developmental programming of adiposity in offspring. Finally, the relative merits of a range of various behavioral approaches targeted at pediatric obesity were covered, together with the specific roles of pharmacotherapy and bariatric surgery in pediatric populations. In summary, pediatric obesity is a very challenging problem that is unprecedented in evolutionary terms; one which has the capacity to negate many of the health benefits that have contributed to the increased longevity observed in the developed world. PMID:24662696

Drug product distribution systems and departmental operations.

PubMed

Hynniman, C E

1991-10-01

Technologies affecting institutional pharmacy practice and the operation of pharmacy departments are reviewed, future developments are outlined, and implications of these developments for pharmacy education are proposed. Computer technology, especially as applied to areas such as artificial intelligence, online information databases, electronic bulletin boards, hospital information systems, and point-of-care systems, will have a strong impact on pharmacy practice and management in the 1990s. Other areas in which growth is likely to be active include bar-code technology, robotics, and automated drug dispensing. The applications of these technologies are described, with particular attention placed on the effects of increased automation on the drug-dispensing function. Technological advances may effect marked reductions in dispensing and medication errors; questions concerning the cost-effectiveness of these new systems remain to be answered. These advances also create new opportunities for clinical involvement by pharmacists; however, a fundamental understanding of computer systems is essential. Current practitioners can benefit from attending seminars, participating in users' groups, and keeping current with the computer literature. Many students now acquire the needed skills in computer laboratories and in the classroom. Technological advances will offer the opportunity for pharmacists to expand their clinical role.

An evolving scientific basis for the prevention and treatment of pediatric obesity.

PubMed

Katzmarzyk, P T; Barlow, S; Bouchard, C; Catalano, P M; Hsia, D S; Inge, T H; Lovelady, C; Raynor, H; Redman, L M; Staiano, A E; Spruijt-Metz, D; Symonds, M E; Vickers, M; Wilfley, D; Yanovski, J A

2014-07-01

The 2013 Pennington Biomedical Research Center's Scientific Symposium focused on the treatment and management of pediatric obesity and was designed to (i) review recent scientific advances in the prevention, clinical treatment and management of pediatric obesity, (ii) integrate the latest published and unpublished findings and (iii) explore how these advances can be integrated into clinical and public health approaches. The symposium provided an overview of important new advances in the field, which led to several recommendations for incorporating the scientific evidence into practice. The science presented covered a range of topics related to pediatric obesity, including the role of genetic differences, epigenetic events influenced by in utero development, pre-pregnancy maternal obesity status, maternal nutrition and maternal weight gain on developmental programming of adiposity in offspring. Finally, the relative merits of a range of various behavioral approaches targeted at pediatric obesity were covered, together with the specific roles of pharmacotherapy and bariatric surgery in pediatric populations. In summary, pediatric obesity is a very challenging problem that is unprecedented in evolutionary terms; one which has the capacity to negate many of the health benefits that have contributed to the increased longevity observed in the developed world.

Biobanking for Personalized Medicine.

PubMed

Liu, Angen; Pollard, Kai

2015-01-01

A biobank is an entity that collects, processes, stores, and distributes biospecimens and relevant data for use in basic, translational, and clinical research. Biobanking of high-quality human biospecimens such as tissue, blood and other bodily fluids along with associated patient clinical information provides a fundamental scientific infrastructure for personalized medicine. Identification of biomarkers that are specifically associated with particular medical conditions such as cancer, cardiovascular disease and neurological disorders are useful for early detection, prevention, and treatment of the diseases. The ability to determine individual tumor biomarkers and to use those biomarkers for disease diagnosis, prognosis and prediction of response to therapy is having a very significant impact on personalized medicine and is rapidly changing the way clinical care is conducted. As a critical requirement for personalized medicine is the availability of a large collection of patient samples with well annotated patient clinical and pathological data, biobanks thus play an important role in personalized medicine advancement. The goal of this chapter is to explore the role of biobanks in personalized medicine and discuss specific needs regarding biobank development for translational and clinical research, especially for personalized medicine advancement.

Biomedical research, development, and engineering at the Johns Hopkins University Applied Physics Laboratory. Annual report 1 October 1978-30 September 1979

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

Not Available

The Medical Institutions of The Johns Hopkins University and The Johns Hopkins University Applied Physics Laboratory have developed a vigorous collaborative program of biomedical research, development, and systems engineering. An important objective of the program is to apply the expertise in engineering, the physical sciences, and systems analysis acquired by APL in defense and space research and development to problems of medical research and health care delivery. This program has grown to include collaboration with many of the clinical and basic science departments of the medical divisions. Active collaborative projects exist in ophthalmology, neurosensory research and instrumentation development, cardiovascular systems,more » patient monitoring, therapeutic and rehabilitation systems, clinical information systems, and clinical engineering. This application of state-of-the-art technology has contributed to advances in many areas of basic medical research and in clinical diagnosis and therapy through improvement of instrumentation, techniques, and basic understanding.« less

Deep learning with convolutional neural network in radiology.

PubMed

Yasaka, Koichiro; Akai, Hiroyuki; Kunimatsu, Akira; Kiryu, Shigeru; Abe, Osamu

2018-04-01

Deep learning with a convolutional neural network (CNN) is gaining attention recently for its high performance in image recognition. Images themselves can be utilized in a learning process with this technique, and feature extraction in advance of the learning process is not required. Important features can be automatically learned. Thanks to the development of hardware and software in addition to techniques regarding deep learning, application of this technique to radiological images for predicting clinically useful information, such as the detection and the evaluation of lesions, etc., are beginning to be investigated. This article illustrates basic technical knowledge regarding deep learning with CNNs along the actual course (collecting data, implementing CNNs, and training and testing phases). Pitfalls regarding this technique and how to manage them are also illustrated. We also described some advanced topics of deep learning, results of recent clinical studies, and the future directions of clinical application of deep learning techniques.

Clinical Pharmacy Consultations Provided by American and Kenyan Pharmacy Students During an Acute Care Advanced Pharmacy Practice Experience

PubMed Central

Pastakia, Sonak D.; Manji, Imran; Kamau, Evelyn; Schellhase, Ellen M.

2011-01-01

Objective To compare the clinical consultations provided by American and Kenyan pharmacy students in an acute care setting in a developing country. Methods The documented pharmacy consultation recommendations made by American and Kenyan pharmacy students during patient care rounds on an advanced pharmacy practice experience at a referral hospital in Kenya were reviewed and classified according to type of intervention and therapeutic area. Results The Kenyan students documented more interventions than American students (16.7 vs. 12.0 interventions/day) and provided significantly more consultations regarding human immunodeficiency virus (HIV) and antibiotics. The top area of consultations provided by American students was cardiovascular diseases. Conclusions American and Kenyan pharmacy students successfully providing clinical pharmacy consultations in a resource-constrained, acute-care practice setting suggests an important role for pharmacy students in the reconciliation of prescriber orders with medication administration records and in providing drug information. PMID:21655396

Ethical and Clinical Considerations at the Intersection of Functional Neuroimaging and Disorders of Consciousness.

PubMed

Byram, Adrian C; Lee, Grace; Owen, Adrian M; Ribary, Urs; Stoessl, A Jon; Townson, Andrea; Illes, Judy

2016-10-01

Recent neuroimaging research on disorders of consciousness provides direct evidence of covert consciousness otherwise not detected clinically in a subset of severely brain-injured patients. These findings have motivated strategic development of binary communication paradigms, from which researchers interpret voluntary modulations in brain activity to glean information about patients' residual cognitive functions and emotions. The discovery of such responsiveness raises ethical and legal issues concerning the exercise of autonomy and capacity for decisionmaking on matters such as healthcare, involvement in research, and end of life. These advances have generated demands for access to the technology against a complex background of continued scientific advancement, questions about just allocation of healthcare resources, and unresolved legal issues. Interviews with professionals whose work is relevant to patients with disorders of consciousness reveal priorities concerning further basic research, legal and policy issues, and clinical considerations.

The evolution of image-guided lumbosacral spine surgery.

PubMed

Bourgeois, Austin C; Faulkner, Austin R; Pasciak, Alexander S; Bradley, Yong C

2015-04-01

Techniques and approaches of spinal fusion have considerably evolved since their first description in the early 1900s. The incorporation of pedicle screw constructs into lumbosacral spine surgery is among the most significant advances in the field, offering immediate stability and decreased rates of pseudarthrosis compared to previously described methods. However, early studies describing pedicle screw fixation and numerous studies thereafter have demonstrated clinically significant sequelae of inaccurate surgical fusion hardware placement. A number of image guidance systems have been developed to reduce morbidity from hardware malposition in increasingly complex spine surgeries. Advanced image guidance systems such as intraoperative stereotaxis improve the accuracy of pedicle screw placement using a variety of surgical approaches, however their clinical indications and clinical impact remain debated. Beginning with intraoperative fluoroscopy, this article describes the evolution of image guided lumbosacral spinal fusion, emphasizing two-dimensional (2D) and three-dimensional (3D) navigational methods.

Navigating the current landscape of clinical genetic testing for inherited retinal dystrophies.

PubMed

Lee, Kristy; Garg, Seema

2015-04-01

Inherited eye disorders are a significant cause of vision loss. Genetic testing can be particularly helpful for patients with inherited retinal dystrophies because of genetic heterogeneity and overlapping phenotypes. The need to identify a molecular diagnosis for retinal dystrophies is particularly important in the era of developing novel gene therapy-based treatments, such as the RPE65 gene-based clinical trials and others on the horizon, as well as recent advances in reproductive options. The introduction of massively parallel sequencing technologies has significantly advanced the identification of novel gene candidates and has expanded the landscape of genetic testing. In a relatively short time clinical medicine has progressed from limited testing options to a plethora of choices ranging from single-gene testing to whole-exome sequencing. This article outlines currently available genetic testing and factors to consider when selecting appropriate testing for patients with inherited retinal dystrophies.

Novel technologies and theoretical models in radiation therapy of cancer patients using 6.3 MeV fast neutrons produced by U-120 cyclotron

NASA Astrophysics Data System (ADS)

Musabaeva, L. I.; Startseva, Zh. A.; Gribova, O. V.; Velikaya, V. V.; Lisin, V. A.

2016-08-01

The analysis of clinical use of neutron therapy with 6 MeV fast neutrons compared to conventional radiation therapy was carried out. The experience of using neutron and mixed neutron and photon therapy in patients with different radio-resistant malignant tumors shows the necessity of further studies and development of the novel approaches to densely-ionizing radiation. The results of dosimetry and radiobiological studies have been the basis for planning clinical programs for neutron therapy. Clinical trials over the past 30 years have shown that neutron therapy successfully destroys radio-resistant cancers, including salivary gland tumors, adenoidcystic carcinoma, inoperable sarcomas, locally advanced head and neck tumors, and locally advanced prostate cancer. Radiation therapy with 6.3 MeV fast neutrons used alone and in combination with photon therapy resulted in improved long-term treatment outcomes in patients with radio-resistant malignant tumors.

Advances in the assessment and prediction of interpersonal violence.

PubMed

Mills, Jeremy F

2005-02-01

This article underscores the weakness of clinical judgment as a mechanism for prediction with examples from other areas in the psychological literature. Clinical judgment has as its Achilles'heel the reliance on a person to incorporate multiple pieces of information while overcoming human judgment errors--a feat insurmountable thus far. The actuarial approach to risk assessment has overcome many of the weaknesses of clinical judgment and has been shown to be a much superior method. Nonetheless, the static/historical nature of the risk factors associated with most actuarial approaches is limiting. Advances in risk prediction will be found in part in the development of dynamic actuarial instruments that will measure both static/historical and changeable risk factors. The dynamic risk factors can be reevaluated on an ongoing basis, and it is proposed that the level of change in dynamic factors necessary to represent a significant change in overall risk will be an interactive function with static risk factors.

Time to rethink the role of the library in educating doctors: driving information literacy in the clinical environment.

PubMed

Simons, Mary R; Morgan, Michael Kerin; Davidson, Andrew Stewart

2012-10-01

Can information literacy (IL) be embedded into the curriculum and clinical environment to facilitate patient care and lifelong learning? The Australian School of Advanced Medicine (ASAM) provides competence-based programs incorporating patient-centred care and lifelong learning. ASAM librarians use outcomes-based educational theory to embed and assess IL into ASAM's educational and clinical environments. A competence-based IL program was developed where learning outcomes were linked to current patients and assessed with checklists. Weekly case presentations included clinicians' literature search strategies, results, and conclusions. Librarians provided support to clinicians' literature searches and assessed their presentations using a checklist. Outcome data showed clinicians' searching skills improved over time; however, advanced MEDLINE searching remained challenging for some. Recommendations are provided. IL learning that takes place in context using measurable outcomes is more meaningful, is enduring, and likely contributes to patient care. Competence-based assessment drives learning in this environment.

Automated Modular Magnetic Resonance Imaging Clinical Decision Support System (MIROR): An Application in Pediatric Cancer Diagnosis

PubMed Central

Zarinabad, Niloufar; Meeus, Emma M; Manias, Karen; Foster, Katharine

2018-01-01

Background Advances in magnetic resonance imaging and the introduction of clinical decision support systems has underlined the need for an analysis tool to extract and analyze relevant information from magnetic resonance imaging data to aid decision making, prevent errors, and enhance health care. Objective The aim of this study was to design and develop a modular medical image region of interest analysis tool and repository (MIROR) for automatic processing, classification, evaluation, and representation of advanced magnetic resonance imaging data. Methods The clinical decision support system was developed and evaluated for diffusion-weighted imaging of body tumors in children (cohort of 48 children, with 37 malignant and 11 benign tumors). Mevislab software and Python have been used for the development of MIROR. Regions of interests were drawn around benign and malignant body tumors on different diffusion parametric maps, and extracted information was used to discriminate the malignant tumors from benign tumors. Results Using MIROR, the various histogram parameters derived for each tumor case when compared with the information in the repository provided additional information for tumor characterization and facilitated the discrimination between benign and malignant tumors. Clinical decision support system cross-validation showed high sensitivity and specificity in discriminating between these tumor groups using histogram parameters. Conclusions MIROR, as a diagnostic tool and repository, allowed the interpretation and analysis of magnetic resonance imaging images to be more accessible and comprehensive for clinicians. It aims to increase clinicians’ skillset by introducing newer techniques and up-to-date findings to their repertoire and make information from previous cases available to aid decision making. The modular-based format of the tool allows integration of analyses that are not readily available clinically and streamlines the future developments. PMID:29720361

Update On Emerging Antivirals For The Management Of Herpes Simplex Virus Infections: A Patenting Perspective

PubMed Central

Vadlapudi, Aswani D.; Vadlapatla, Ramya K.; Mitra, Ashim K.

2015-01-01

Herpes simplex virus (HSV) infections can be treated efficiently by the application of antiviral drugs. The herpes family of viruses is responsible for causing a wide variety of diseases in humans. The standard therapy for the management of such infections includes acyclovir (ACV) and penciclovir (PCV) with their respective prodrugs valaciclovir and famciclovir. Though effective, long term prophylaxis with the current drugs leads to development of drug-resistant viral isolates, particularly in immunocompromised patients. Moreover, some drugs are associated with dose-limiting toxicities which limit their further utility. Therefore, there is a need to develop new antiherpetic compounds with different mechanisms of action which will be safe and effective against emerging drug resistant viral isolates. Significant advances have been made towards the design and development of novel antiviral therapeutics during the last decade. As evident by their excellent antiviral activities, pharmaceutical companies are moving forward with several new compounds into various phases of clinical trials. This review provides an overview of structure and life cycle of HSV, progress in the development of new therapies, update on the advances in emerging therapeutics under clinical development and related recent patents for the treatment of Herpes simplex virus infections. PMID:23331181

Important role of translational science in rare disease innovation, discovery, and drug development.

PubMed

Pariser, Anne R; Gahl, William A

2014-08-01

Rare diseases play a leading role in innovation and the advancement of medical and pharmaceutical science. Most rare diseases are genetic disorders or atypical manifestations of infectious, immunologic, or oncologic diseases; they all provide opportunities to study extremes of human pathology and provide insight into both normal and aberrant physiology. Recently, drug development has become increasingly focused on classifying diseases largely on genetic grounds; this has allowed the identification of molecularly defined targets and the development of targeted therapies. Clinical trials are now focusing on progressively smaller subgroups within both common and rare disease populations, often based on genetic tests or biomarkers. Drug developers, researchers, and regulatory agencies face a variety of challenges throughout the life cycle of drug research and development for rare diseases. These include the small numbers of patients available for study, lack of knowledge of the disease's natural history, incomplete understanding of the basic mechanisms causing the disorder, and variability in disease severity, expression, and course. Traditional approaches to rare disease clinical research have not kept pace with advances in basic science, and increased attention to translational science is needed to address these challenges, especially diagnostic testing, registries, and novel trial designs.

Space Biosensor Systems: Implications for Technology Transfer

NASA Technical Reports Server (NTRS)

Hines, J. W.; Somps, C. J.; Madou, M.; Imprescia, Clifford C. (Technical Monitor)

1997-01-01

To meet the need for continuous, automated monitoring of animal subjects, including; humans, during space flight, NASA is developing advanced physiologic sensor and biotelemetry system technologies. The ability to continuously track basic physiological parameters, such as heart rate, blood pH, and body temperature, in untethered subjects in space is a challenging task. At NASA's Ames Research Center, where a key focus is gravitational biology research, engineers have teamed with life scientists to develop wireless sensor systems for automated physiologic monitoring of animal models as small as the rat. This technology is also being adapted, in collaboration with medical professionals, to meet human clinical monitoring needs both in space and on the ground. Thus, these advanced monitoring technologies have important dual-use functions; they meet space flight data collection requirements and constraints, while concurrently addressing a number of monitoring and data acquisition challenges on the ground in areas of clinical monitoring and biomedical research. Additional applications for these and related technologies are being sought and additional partnerships established that enhance development efforts, reduce costs and facilitate technology infusion between the public and private sectors. This paper describes technology transfer and co-development projects that have evolved out of NASA's miniaturized, implantable chemical sensor development efforts.

Better infrastructure for critical care trials: nomenclature, etymology, and informatics.

PubMed

Singh, Jeffrey M; Ferguson, Niall D

2009-01-01

The goals of this review article are to review the importance and value of standardized definitions in clinical research, as well as to propose the necessary tools and infrastructure needed to advance nosology and medial taxonomy to improve the quality of clinical trials in the field of critical care. We searched MEDLINE for relevant articles, reviewed those selected and their reference lists, and consulted personal files for relevant information. When the pathobiology of diseases is well understood, standard disease definitions can be extremely specific and precise; however, when the pathobiology of the disease is less well understood or more complex, biological markers may not be diagnostically useful or even available. In these cases, syndromic definitions effectively classify and group illnesses with similar symptoms and clinical signs. There is no clear gold standard for the diagnosis of many clinical entities in the intensive care unit, including notably both acute respiratory distress syndrome and sepsis. There are several types of consensus methods that can be used to explicate the judgmental approach that is often needed in these cases, including interactive or consensus groups, the nominal group technique, and the Delphi technique. Ideally, the definition development process will create clear and unambiguous language in which each definition accurately reflects the current understanding of the disease state. The development, implementation, evaluation, revision, and reevaluation of standardized definitions are keys for advancing the quality of clinical trials in the critical care arena.

Developing virtual patients for medical microbiology education.

PubMed

McCarthy, David; O'Gorman, Ciaran; Gormley, Gerry J

2013-12-01

The landscape of medical education is changing as students embrace the accessibility and interactivity of e-learning. Virtual patients are e-learning resources that may be used to advance microbiology education. Although the development of virtual patients has been widely considered, here we aim to provide a coherent approach for clinical educators. Copyright © 2013 Elsevier Ltd. All rights reserved.

Development and Pilot Evaluation of a Psychosocial Intervention Program for Patients with Age-Related Macular Degeneration

ERIC Educational Resources Information Center

Birk, Tanja; Hickl, Susanne; Wahl, Hans-Werner; Miller, Daniel; Kammerer, Annette; Holz, Frank; Becker, Stefanie; Volcker, Hans E.

2004-01-01

Purpose: The psychosocial needs of patients suffering from severe visual loss associated with advanced age-related macular degeneration (ARMD) are generally ignored in the clinical routine. The aim of this study was to develop and evaluate a psychosocial intervention program for ARMD patients. This intervention program was based on six modules…

Interspecies chimeras.

PubMed

Suchy, Fabian; Nakauchi, Hiromitsu

2018-05-30

By probing early embryogenesis and regeneration, interspecies chimeras provide a unique platform for discovery and clinical use. Although efficient generation of human:animal chimeric embryos remains elusive, recent advancements attempt to overcome incompatibilities in xenogeneic development and transplantation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Extreme-Scale Computing Project Aims to Advance Precision Oncology | Frederick National Laboratory for Cancer Research

Cancer.gov

Two government agencies and five national laboratories are collaborating to develop extremely high-performance computing capabilities that will analyze mountains of research and clinical data to improve scientific understanding of cancer, predict dru

Extreme-Scale Computing Project Aims to Advance Precision Oncology | Poster

Cancer.gov

Two government agencies and five national laboratories are collaborating to develop extremely high-performance computing capabilities that will analyze mountains of research and clinical data to improve scientific understanding of cancer, predict drug response, and improve treatments for patients.

Transforming practice into clinical scholarship.

PubMed

Limoges, Jacqueline; Acorn, Sonia

2016-04-01

The aims of this paper were to explicate clinical scholarship as synonymous with the scholarship of application and to explore the evolution of scholarly practice to clinical scholarship. Boyer contributed an expanded view of scholarship that recognized various approaches to knowledge production beyond pure research (discovery) to include the scholarship of integration, application and teaching. There is growing interest in using Boyer's framework to advance knowledge production in nursing but the discussion of clinical scholarship in relation to Boyer's framework is sparse. Discussion paper. Literature from 1983-2015 and Boyer's framework. When clinical scholarship is viewed as a synonym for Boyer's scholarship of application, it can be aligned to this well established framework to support knowledge generated in clinical practice. For instance, applying the three criteria for scholarship (documentation, peer review and dissemination) can ensure that the knowledge produced is rigorous, available for critique and used by others to advance nursing practice and patient care. Understanding the differences between scholarly practice and clinical scholarship can promote the development of clinical scholarship. Supporting clinical leaders to identify issues confronting nursing practice can enable scholarly practice to be transformed into clinical scholarship. Expanding the understanding of clinical scholarship and linking it to Boyer's scholarship of application can assist nurses to generate knowledge that addresses clinical concerns. Further dialogue about how clinical scholarship can address the theory-practice gap and how publication of clinical scholarship could be expanded given the goals of clinical scholarship is warranted. © 2016 John Wiley & Sons Ltd.

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 threat of a 10% budget cut, the nation's Clinical Trials Cooperative Groups reduced the number of patients participating in clinical trials by almost 2,000 and senior researchers report that many of the brightest young minds no longer see the promise of a career in science, choosing other careers instead. It's time to renew the nation's commitment to cancer research. Without additional support, the opportunity to build on the extraordinary progress to date will be lost or delayed. This report demonstrates the essential role that clinical cancer research plays in finding new and better ways to care for the more than 1.4 million people expected to be diagnosed with cancer this year. I want to thank the Editorial Board members, the Specialty Editors, and the ASCO Cancer Communications Committee for their dedicated work to develop this report. I hope you find it useful. Sincerely, Nancy E. Davidson, MD President American Society of Clinical Oncology.

Safeguarding the future of independent, academic clinical cancer research in Europe for the benefit of patients.

PubMed

Negrouk, Anastassia; Lacombe, Denis; Cardoso, Fatima; Morin, Franck; Carrasco, Eva; Maurel, Joan; Maibach, Rudolf; Aranda, Enrique; Marais, Richard; Stahel, Rolf A

2017-01-01

Cancer is a complex disease that is constantly evolving. It is now the most common cause of death in Europe after cardiovascular diseases. There are inequalities among European countries, potentially unsustainable healthcare systems impacting quality of cancer care and increasing number of patients with cancer with rare conditions. Clinical and translational research are the backbone in establishing scientific advances as novel treatments and advancing progress to the benefit of patients. Commercially sponsored clinical trials are responsible for developing new medicines that can treat various disease areas, including cancer. It is important to note, however, that these clinical trials only assess the viability of compounds that are chosen by a commercial entity that funds the entire process. By their design and focus, these trials need to fulfil commercial interests and market expectations, which do not always coincide with patients' needs. As soon or even before novel treatments and compounds obtain formal market authorisation, academia will take these existing and new medicines to further conduct research in order to optimise their use, develop new combinations and with a strong focus on the patients and their needs. Established standard of care most commonly relies on clinical cancer research stemming from non-commercial entities, cooperative groups or academic clinical research. This article provides a consensus on the definition of academic research, illustrates its added value and suggests and calls to European Union institutions to support this type of research for the benefit of patients.

The physiological challenges of the 1952 Copenhagen poliomyelitis epidemic and a renaissance in clinical respiratory physiology

PubMed Central

West, John B.

2005-01-01

The 1952 Copenhagen poliomyelitis epidemic provided extraordinary challenges in applied physiology. Over 300 patients developed respiratory paralysis within a few weeks, and the ventilator facilities at the infectious disease hospital were completely overwhelmed. The heroic solution was to call upon 200 medical students to provide round-the-clock manual ventilation using a rubber bag attached to a tracheostomy tube. Some patients were ventilated in this way for several weeks. A second challenge was to understand the gas exchange and acid-base status of these patients. At the onset of the epidemic, the only measurement routinely available in the hospital was the carbon dioxide concentration in the blood, and the high values were initially misinterpreted as a mysterious “alkalosis.” However, pH measurements were quickly instituted, the PCO2 was shown to be high, and modern clinical respiratory acid-base physiology was born. Taking a broader view, the problems highlighted by the epidemic underscored the gap between recent advances made by physiologists and their application to the clinical environment. However, the 1950s ushered in a renaissance in clinical respiratory physiology. In 1950 the coverage of respiratory physiology in textbooks was often woefully inadequate, but the decade saw major advances in topics such as mechanics and gas exchange. An important development was the translation of the new knowledge from departments of physiology to the clinical setting. In many respects, this period was therefore the beginning of modern clinical respiratory physiology. PMID:16020437

Recent developments of cyclotron produced radionuclides for nuclear cardiology

NASA Astrophysics Data System (ADS)

Kulkarni, P. V.; Jansen, D. E.; Corbett, J. R.

1987-04-01

For over a decade myocardial perfusion imaging with thallium-201, a cyclotron product, has been routinely used in clinical medicine. Recent advances have allowed the efficient production of very high purity (> 99.8%) iodine-123. New metabolically active 123I labeled radiopharmaceuticals, including alkyl and phenyl fatty acids, and norepinephrine analogs, have been developed and are undergoing clinical trials. Fab' fragments of monoclonal antibodies to cardiac myosin have been labeled with indium-111 ( 111In) and are undergoing clinical evaluation for imaging myocardial infarcts. Monoclonal antibodies to platelets, fibrin, and the thrombolytic agent, tissue plasminogen activator (TPA), have recently been labeled with 111In. Together these developments in radiotracers and instrumentation should have a significant impact on the future of cardiovascular nuclear medicine. This manuscript will discuss developments in single photon emitting radiotracers for myocardial imaging.

Clinical trial investigates experimental drug for advanced pancreatic cancer | Center for Cancer Research

Cancer.gov

The pancreas, a large gland that sits behind the stomach, produces enzymes that aid digestion and hormones that regulate blood sugar. Pancreatic cancer develops when cells that make up the ducts in the pancreas start to grow out of control. Udo Rudloff, M.D., is leading a clinical trial of a combination immunotherapy regimen to optimally help the immune system attack the tumor.

Glycosylated haemoglobin: measurement and clinical use.

PubMed

Peacock, I

1984-08-01

The discovery, biochemistry, laboratory determination, and clinical application of glycosylated haemoglobins are reviewed. Sources of error are discussed in detail. No single assay method is suitable for all purposes, and in the foreseeable future generally acceptable standards and reference ranges are unlikely to be agreed. Each laboratory must establish its own. Nevertheless, the development of glycosylated haemoglobin assays is an important advance. They offer the best available means of assessing diabetic control.

Current Progress of siRNA/shRNA Therapeutics in Clinical Trials

PubMed Central

Burnett, John C.; Rossi, John J.; Tiemann, Katrin

2012-01-01

Through a mechanism known as RNA interference (RNAi), small interfering RNA (siRNA) molecules can target complementary mRNA strands for degradation, thus specifically inhibiting gene expression. The ability of siRNAs to inhibit gene expression offers a mechanism that can be exploited for novel therapeutics. Indeed, over the past decade, at least 21 siRNA therapeutics have been developed for more than a dozen diseases, including various cancers, viruses, and genetic disorders. Like other biological drugs, RNAi-based therapeutics often require a delivery vehicle to transport them to the targeted cells. Thus, the clinical advancement of numerous siRNA drugs has relied on the development of siRNA carriers including biodegradable nanoparticles, lipids, bacteria, and attenuated viruses. Most therapies permit systemic delivery of the siRNA drug, while others use ex vivo delivery by autologous cell therapy. For some of the drugs, advancements in bioengineering and nanotechnology have led to improved control of delivery and release of the siRNA. Likewise, progress in molecular biology has allowed for improved design of the siRNA molecules. Here, we provide an overview of siRNA therapeutics in clinical trials, including their clinical progress, the challenges they have encountered, and the future they hold in the treatment of human diseases. PMID:21744502

Current progress of siRNA/shRNA therapeutics in clinical trials.

PubMed

Burnett, John C; Rossi, John J; Tiemann, Katrin

2011-09-01

Through a mechanism known as RNA interference (RNAi), small interfering RNA (siRNA) molecules can target complementary mRNA strands for degradation, thus specifically inhibiting gene expression. The ability of siRNAs to inhibit gene expression offers a mechanism that can be exploited for novel therapeutics. Indeed, over the past decade, at least 21 siRNA therapeutics have been developed for more than a dozen diseases, including various cancers, viruses, and genetic disorders. Like other biological drugs, RNAi-based therapeutics often require a delivery vehicle to transport them to the targeted cells. Thus, the clinical advancement of numerous siRNA drugs has relied on the development of siRNA carriers, including biodegradable nanoparticles, lipids, bacteria, and attenuated viruses. Most therapies permit systemic delivery of the siRNA drug, while others use ex vivo delivery by autologous cell therapy. Advancements in bioengineering and nanotechnology have led to improved control of delivery and release of some siRNA therapeutics. Likewise, progress in molecular biology has allowed for improved design of the siRNA molecules. Here, we provide an overview of siRNA therapeutics in clinical trials, including their clinical progress, the challenges they have encountered, and the future they hold in the treatment of human diseases. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An automated smartphone-based diagnostic assay for point-of-care semen analysis.

PubMed

Kanakasabapathy, Manoj Kumar; Sadasivam, Magesh; Singh, Anupriya; Preston, Collin; Thirumalaraju, Prudhvi; Venkataraman, Maanasa; Bormann, Charles L; Draz, Mohamed Shehata; Petrozza, John C; Shafiee, Hadi

2017-03-22

Male infertility affects up to 12% of the world's male population and is linked to various environmental and medical conditions. Manual microscope-based testing and computer-assisted semen analysis (CASA) are the current standard methods to diagnose male infertility; however, these methods are labor-intensive, expensive, and laboratory-based. Cultural and socially dominated stigma against male infertility testing hinders a large number of men from getting tested for infertility, especially in resource-limited African countries. We describe the development and clinical testing of an automated smartphone-based semen analyzer designed for quantitative measurement of sperm concentration and motility for point-of-care male infertility screening. Using a total of 350 clinical semen specimens at a fertility clinic, we have shown that our assay can analyze an unwashed, unprocessed liquefied semen sample with <5-s mean processing time and provide the user a semen quality evaluation based on the World Health Organization (WHO) guidelines with ~98% accuracy. The work suggests that the integration of microfluidics, optical sensing accessories, and advances in consumer electronics, particularly smartphone capabilities, can make remote semen quality testing accessible to people in both developed and developing countries who have access to smartphones. Copyright © 2017, American Association for the Advancement of Science.

Motor Rehabilitation Using Kinect: A Systematic Review.

PubMed

Da Gama, Alana; Fallavollita, Pascal; Teichrieb, Veronica; Navab, Nassir

2015-04-01

Interactive systems are being developed with the intention to help in the engagement of patients on various therapies. Amid the recent technological advances, Kinect™ from Microsoft (Redmond, WA) has helped pave the way on how user interaction technology facilitates and complements many clinical applications. In order to examine the actual status of Kinect developments for rehabilitation, this article presents a systematic review of articles that involve interactive, evaluative, and technical advances related to motor rehabilitation. Systematic research was performed in the IEEE Xplore and PubMed databases using the key word combination "Kinect AND rehabilitation" with the following inclusion criteria: (1) English language, (2) page number >4, (3) Kinect system for assistive interaction or clinical evaluation, or (4) Kinect system for improvement or evaluation of the sensor tracking or movement recognition. Quality assessment was performed by QualSyst standards. In total, 109 articles were found in the database research, from which 31 were included in the review: 13 were focused on the development of assistive systems for rehabilitation, 3 in evaluation, 3 in the applicability category, 7 on validation of Kinect anatomic and clinical evaluation, and 5 on improvement techniques. Quality analysis of all included articles is also presented with their respective QualSyst checklist scores. Research and development possibilities and future works with the Kinect for rehabilitation application are extensive. Methodological improvements when performing studies on this area need to be further investigated.

Impact of Blood Type, Functional Polymorphism (T-1676C) of the COX-1 Gene Promoter and Clinical Factors on the Development of Peptic Ulcer during Cardiovascular Prophylaxis with Low-Dose Aspirin

PubMed Central

Wang, Pin-Yao; Chen, Hsiu-Ping; Chen, Angela; Tsay, Feng-Woei; Kao, Sung-Shuo; Peng, Nan-Jing; Tseng, Hui-Hwa; Hsu, Ping-I

2014-01-01

Aims. To investigate the impact of blood type, functional polymorphism (T-1676C) of the COX-1 gene promoter, and clinical factors on the development of peptic ulcer during cardiovascular prophylaxis with low-dose aspirin. Methods. In a case-control study including 111 low-dose aspirin users with peptic ulcers and 109 controls (asymptomatic aspirin users), the polymorphism (T-1676C) of the COX-1 gene promoter was genotyped, and blood type, H pylori status, and clinical factors were assessed. Results. Univariate analysis showed no significant differences in genotype frequencies of the COX-1 gene at position -1676 between the peptic ulcer group and control group. Multivariate analysis revealed that blood type O, advanced age, history of peptic ulcer, and concomitant use of NSAID were the independent risk factors for the development of peptic ulcer with the odds ratios of the 2.1, 3.1, 27.6, and 2.9, respectively. Conclusion. The C-1676T polymorphism in the COX-1 gene promoter is not a risk factor for ulcer formation during treatment with low-dose aspirin. Blood type O, advanced age, history of peptic ulcer, and concomitant use of NSAID are of independent significance in predicting peptic ulcer development during treatment with low-dose aspirin. PMID:25243161

Recent advances in treating Parkinson’s disease

PubMed Central

Oertel, Wolfgang H.

2017-01-01

This article summarizes (1) the recent achievements to further improve symptomatic therapy of motor Parkinson’s disease (PD) symptoms, (2) the still-few attempts to systematically search for symptomatic therapy of non-motor symptoms in PD, and (3) the advances in the development and clinical testing of compounds which promise to offer disease modification in already-manifest PD. However, prevention (that is, slowing or stopping PD in a prodromal stage) is still a dream and one reason for this is that we have no consensus on primary endpoints for clinical trials which reflect the progression in prodromal stages of PD, such as in rapid eye movement sleep behavior disorder (RBD) —a methodological challenge to be met in the future. PMID:28357055

Maintenance of nutritional status in patients with cystic fibrosis: new and emerging therapies

PubMed Central

Kalnins, Daina; Wilschanski, Michael

2012-01-01

Poor clinical outcomes in cystic fibrosis are often associated with undernutrition. Normal growth and development should be achieved in cystic fibrosis, and nutritional counseling is paramount at all ages. Prevention and early detection of growth failure is the key to successful nutritional intervention. The advance in nutritional management is certainly one factor that has contributed to the improved survival in recent decades. This review outlines the major nutritional parameters in the management of the patient with cystic fibrosis, including recent advances in pancreatic enzyme replacement therapy and fat-soluble vitamin therapy. There are sections on complicated clinical situations which directly affect nutrition, for example, before and after lung transplantation, cystic fibrosis-related diabetes, and bone health. PMID:22787388

Advances in understanding Giardia: determinants and mechanisms of chronic sequelae

PubMed Central

Sartor, R. Balfour

2015-01-01

Giardia lamblia is a flagellated protozoan that is the most common cause of intestinal parasitic infection in children living in resource-limited settings. The pathogenicity of Giardia has been debated since the parasite was first identified, and clinical outcomes vary across studies. Among recent perplexing findings are diametrically opposed associations between Giardia and acute versus persistent diarrhea and a poorly understood potential for long-term sequelae, including impaired child growth and cognitive development. The mechanisms driving these protean clinical outcomes remain elusive, but recent advances suggest that variability in Giardia strains, host nutritional status, the composition of microbiota, co-infecting enteropathogens, host genetically determined mucosal immune responses, and immune modulation by Giardia are all relevant factors influencing disease manifestations after Giardia infection. PMID:26097735

Applications of iQID cameras

NASA Astrophysics Data System (ADS)

Han, Ling; Miller, Brian W.; Barrett, Harrison H.; Barber, H. Bradford; Furenlid, Lars R.

2017-09-01

iQID is an intensified quantum imaging detector developed in the Center for Gamma-Ray Imaging (CGRI). Originally called BazookaSPECT, iQID was designed for high-resolution gamma-ray imaging and preclinical gamma-ray single-photon emission computed tomography (SPECT). With the use of a columnar scintillator, an image intensifier and modern CCD/CMOS sensors, iQID cameras features outstanding intrinsic spatial resolution. In recent years, many advances have been achieved that greatly boost the performance of iQID, broadening its applications to cover nuclear and particle imaging for preclinical, clinical and homeland security settings. This paper presents an overview of the recent advances of iQID technology and its applications in preclinical and clinical scintigraphy, preclinical SPECT, particle imaging (alpha, neutron, beta, and fission fragment), and digital autoradiography.

Developing a Peer Mentorship Program to Increase Competence in Clinical Supervision in Clinical Psychology Doctoral Training Programs.

PubMed

Foxwell, Aleksandra A; Kennard, Beth D; Rodgers, Cynthia; Wolfe, Kristin L; Cassedy, Hannah F; Thomas, Anna

2017-12-01

Supervision has recently been recognized as a core competency for clinical psychologists. This recognition of supervision as a distinct competency has evolved in the context of an overall focus on competency-based education and training in health service psychology, and has recently gained momentum. Few clinical psychology doctoral programs offer formal training experiences in providing supervision. A pilot peer mentorship program (PMP) where graduate students were trained in the knowledge and practice of supervision was developed. The focus of the PMP was to develop basic supervision skills in advanced clinical psychology graduate students, as well as to train junior doctoral students in fundamental clinical and practical skills. Advanced doctoral students were matched to junior doctoral students to gain experience in and increase knowledge base in best practices of supervision skills. The 9-month program consisted of monthly mentorship meetings and three training sessions. The results suggested that mentors reported a 30% or more shift from the category of not competent to needs improvement or competent, in the following supervision competencies: theories of supervision, improved skill in supervision modalities, acquired knowledge in supervision, and supervision experience. Furthermore, 50% of the mentors reported that they were not competent in supervision experience at baseline and only 10% reported that they were not competent at the end of the program. Satisfaction data suggested that satisfaction with the program was high, with 75% of participants indicating increased knowledge base in supervision, and 90% indicating that it was a positive addition to their training program. This program was feasible and acceptable and appears to have had a positive impact on the graduate students who participated. Students reported both high satisfaction with the program as well as an increase in knowledge base and experience in supervision skills.

Growth and development of a new subspecialty: pediatric hepatology.

PubMed

Balistreri, William F

2013-08-01

Several major forces converged to catalyze the formal emergence of a body of knowledge and an organized focus on disorders of the liver in early life. Attendant to the development of a focused clinical subspecialty the pace of patient- and laboratory-based research in the field quickened in parallel to decipher the consequences of genetic or metabolic aberrations on immature liver structure and function. The key research observations that catalyzed the emergence and subsequent rapid growth of Pediatric Hepatology include: (1) an understanding of the dynamic events occurring during hepatobiliary development and the importance of these physiologic variables that occur during liver maturation; (2) the recognition of the unique nature of inherited and acquired liver diseases that affect infants and children-such as biliary atresia and Reye's syndrome; and (3) redefinition of the once obscure inherited intrahepatic cholestatic diseases of the liver, which, in turn, provided insight into normal and abnormal hepatobiliary physiology. The clinical advances were highlighted by the development of specific approaches to the diagnosis and management of liver disease in infants and children, including both liver transplantation and nontransplant treatment options. These seminal events led to the expansion of the workforce, creating a critical mass consisting of individuals with focused, specialized skills and techniques. In-depth expertise allowed more accurate diagnosis and highly effective treatment strategies for advanced hepatobiliary disease in children. The demand for pediatric clinicians with experience in advanced hepatology allowed sub-sub-specialization to flourish. Continued maturation of the field led to definition of hepatology-focused curricular elements and educational content for Pediatric Gastroenterology training programs, and subsequently the development of program requirements for those who wished to acquire additional training in Pediatric Hepatology. A significant rite of passage was marked by the election of pediatric hepatologists to leadership positions in the American Association for the Study of Liver Diseases (AASLD). Further validation of the field occurred with approval of the petition for establishing a Certificate of Added Qualification in Transplant Hepatology by the American Board of Pediatrics. Here I relate my perspective on the history of the advances in our field and the contributions of many of the clinicians and scientists whose efforts led to the development of focused clinical, research, and training programs that improved the care of children with diseases of the liver. Copyright © 2013 by the American Association for the Study of Liver Diseases.

Use of health information technology to advance evidence-based care: lessons from the VA QUERI program.

PubMed

Hynes, Denise M; Weddle, Timothy; Smith, Nina; Whittier, Erika; Atkins, David; Francis, Joseph

2010-01-01

As the Department of Veterans Affairs (VA) Health Services Research and Development Service's Quality Enhancement Research Initiative (QUERI) has progressed, health information technology (HIT) has occupied a crucial role in implementation research projects. We evaluated the role of HIT in VA QUERI implementation research, including HIT use and development, the contributions implementation research has made to HIT development, and HIT-related barriers and facilitators to implementation research. Key informants from nine disease-specific QUERI Centers. Documentation analysis of 86 implementation project abstracts followed up by semi-structured interviews with key informants from each of the nine QUERI centers. We used qualitative and descriptive analyses. We found: (1) HIT provided data and information to facilitate implementation research, (2) implementation research helped to further HIT development in a variety of uses including the development of clinical decision support systems (23 of 86 implementation research projects), and (3) common HIT barriers to implementation research existed but could be overcome by collaborations with clinical and administrative leadership. Our review of the implementation research progress in the VA revealed interdependency on an HIT infrastructure and research-based development. Collaboration with multiple stakeholders is a key factor in successful use and development of HIT in implementation research efforts and in advancing evidence-based practice.